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C. elegans Neuronal Development, Synaptic Function & Behavior Topic Meeting 2018 Madison, WI June 25 - June 28, 2018

C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior

C. elegans Neuronal Development, Synaptic Function & Behavior Topic Meeting 2018 Monday, June 25 – Thursday, June 28, 2018 University of Wisconsin-Madison Wisconsin Union 800 Langdon Street Madison, Wisconsin 53706 Meeting Organizers Denise Ferkey, University at Buffalo (SUNY) ([email protected]) Jon Pierce, University of Texas at Austin ([email protected]) Ahna Skop, University of Wisconsin-Madison ([email protected]) (local organizer)

Abstract Selection Committee Michael Ailion, University of Washington, USA Jihong Bai, University of Washington, USA Arantza Barrios, University College of London, UK Kevin Collins, University of Miami, USA Mei Ding, Chinese Academy of Sciences, China Sandra Enchilada, Scripps Research Institute, USA Sarah Hall, Syracuse University, USA Gal Haspel, New Jersey Institute of Technology, USA Gunther Hollopeter, Cornell University, USA Heather Hundley, Indiana University, USA Jagan Srinivasan, Worcester Polytechnic Institute, USA


ACKNOWLEDGEMENTS All sponsoring companies and University of Wisconsin-Madison Memorial Union Conference Services Cover Art: Original design by Tari Tan For emergencies, please call (608) 228-1183 or stop by the Annex Room (Conference Headquarters)

TABLE OF CONTENTS Sponsors………………………………………………………………..ii Conference Schedule………………………………………………..iii Oral and Poster Presentation List………………………………..xii Oral Presentations…………………………………………………….1 Poster Presentations………………………………………………..70 Author Index…………………………………………………………245 Notes………………………………………………………………….258 Memorial Union Building Map……………………………………262 Local Madison Hotel Map………………………………………….263

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SPONSORS

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C. elegans Neuronal Development, Synaptic Function & Behavior Conference Program Monday, June 25th 12 noon – 7:30 pm 12 noon – 9:00 pm

Registration Check-In Poster Set-up

5:00 pm – 7:30 pm

Opening Reception

Annex Room Great Hall/Reception Room Tripp Commons

7:30 pm – 10:00 pm Oral Session #1 Shannon Hall Neural Circuits and Behavior Chairs: Chris Fang-Yen (University of Pennsylvania) & Saul Kato (UCSF) 7:30 pm

Opening Comments & Introductions – Organizers

7:40 pm

Plenary: Manuel Zimmer, Research Institute of Molecular Pathology, Austria Nested Neuronal Oscillators Orchestrate Motor Actions Across Timescales

8:10 pm

Alon Zaslaver (Lab: Zaslaver) Principles of Neural Coding for Efficient Navigation in Gradients

8:25 pm

Qiang Liu (Lab: Bargmann) C. elegans Olfactory Neurons Fire Calcium-Mediated All-or-None Action Potentials

8:40 pm

Julia Riedi (Lab: Zimmer) A Tyraminergic Feedback-Loop Filters Reafferent Perception of Self-Movement in C. elegans Chemosensation

8:55 pm

Steven Flavell (Lab: Flavell) The ASICs DEL-7 and DEL-3 Mediate Food Responses in an Enteric Serotonergic Neuron that Drives Persistent Behaviors

9:10 pm

Tianqi Xu (Lab: Wen) How does an animal move? An integrative model of C. elegans forward locomotion

9:25 pm

Shangbang Gao (Lab: Gao) Excitatory Motor Neurons are Local Oscillators for Reverse Locomotion Community Resources

9:40 pm

Oliver Hobert & Hang Lu Live Imaging of the C. elegans Connectome

NeuroNex

9:50 pm

Marc Hammarlund, David Miller, Nenad Sestan & Oliver Hobert CeNGEN The C. elegans Neuronal Gene Expression Map and Network (CeNGEN)

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Tuesday, June 26th 7:00 am – 5:00 pm

Registration Continues

8:00 am – 9:00 am

Light Breakfast Buffet

Annex Room Shannon Hall Lobby

9:00 am – 12:30 pm Oral Session #2 Shannon Hall Neurodevelopment Chairs: Shaul Yogev (Yale University) & Meital Oren-Suissa (Weizmann Institute) 9:00 am

Plenary: Massimo Hilliard, Queensland Brain Institute, Australia Axonal Fusion: An Alternative Mechanism to Repair Injured Axons

9:30 am

Tyler Buddell (Lab: Quinn) An Autism-Causing Mutation Disrupts Axon Termination by Misregulating Lysosome Function

9:45 am

Mei Ding (Lab: Ding) Robo/SAX-3 Functions as a Wnt Co-Receptor During Directional Neurite Outgrowth in C. elegans

10:00 am

Paschalis Kratsios (Lab: Kratsios) A Transcription Factor Titration Mechanism for the Establishment and Maintenance of Neuron Identity

10:15 am

Anthony Santella (Lab: Bao) WormGUIDES: Assembling and Accessing a Complete, Integrated Record of Neural Development

10:30 – 10:50 am

Refreshment Break

10:50 am

Kat McCormick NemaMetrix Connecting Genes with Phenotypes for Epilepsy and Neurodegenerative Disease

11:00 am

Maxwell Heiman (Lab: Heiman) A Different Kind of Dendrite-Glia Interaction in C. elegans

11:15 am

Nelson Ramirez (Lab: Buelow) “The Creation of Dendrites”: Axon-Dependent Dendritic Development and Maintenance in Somatosensory Neurons

11:30 am

Ardalan Hendi Axonal Tiling in D-Type Motor Neurons

(Lab: Mizumoto)

11:45 am

Wen Chen and Todd Harris An Update about WormBase Tools

WormBase

12:30 – 2:00 pm

Luncheon Buffet

Shannon Hall Lobby

Tripp Commons iv

C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior 2:00 pm – 5:30 pm

Oral Session #3 Shannon Hall Synaptic Function and Modulation Chairs: Heather Bennett (Bard College) & Lizhen Chen (UTHSC-San Antonio)

2:00 pm

Plenary: Chris Li, City College of New York, USA Multiple Roles of apl-1, the C. elegans Human APP Orthologue

2:30 pm

Iris Hardege (Lab: Schafer) Identification of New Ionotropic Receptors for Monoamines and Other Neurotransmitters

2:45 pm

Wookyu Kang (Lab: Alkema) Bacterial Diet Modulates Cholinergic Signaling Through Vitamin B12-Dependent Metabolic Changes in the Intestine

3:00 pm

Ashley Martin (Lab: Richmond) Regulation of the C. elegans Nicotinic Acetylcholine Receptor ACR-16 is CalciumDependent

3:15 pm

Kotaro Kimura (Lab: Kimura) Metabotropic and Ionotropic Glutamate Receptors Coordinately Regulate Olfactory Learning in AIB Interneurons

3:30 – 3:50 pm

Refreshment Break

3:50 pm

Mikalai Malinouski UnionBiometrica Enhanced High-Throughput Phenotyping of C. elegans using the COPAS Vision Flow Cytometer with Imaging Capabilities

4:00 pm

Peter Juo (Lab: Juo) Vascular Endothelial Growth Factor (VEGF) Receptor-related VER-1 and VER-4 Regulate Glutamatergic Behavior by Promoting Cell Surface Levels of GLR-1 Glutamate Receptors

4:15 pm

Jan Watteyne (Lab: Schoofs) Neuromedin U Signaling in Experience-Dependent Salt Chemotaxis

4:30 pm

Timothy Cheung Slowpoke, Where'd You Go?

4:45 pm

Irini Topalidou (Lab: Ailion) Modulation of the NCA Ion Channels by Dopamine, GRK-2, and ERK Signaling

5:00 pm

May Dobosiewicz (Lab: Bargmann) Chemical and Electrical Synapses Cooperate in a Circuit Motif for Sensory Integration

5:15 pm

Bruce Bamber (Lab: Bamber) Serotonin Disinhibits the ASH Nociceptive Neurons by Suppressing Ca2+-Dependent Negative Feedback

5:30 – 7:00 pm

Dinner Buffet

Shannon Hall Lobby

(Lab: Kim)

Tripp Commons v

C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior 7:00 pm – 8:30 pm

Oral Session #4 Technical Advances Chair: Steven Flavell (Picower Institute - MIT)

7:00 pm

Plenary: Shawn Lockery, University of Oregon, USA Nematode Research Technology: The Future is Simple

7:30 pm

Navin Pokala (Lab: Pokala) The Development of a Synthetic Neurotransmission System

7:45 pm

Kathleen Bates (Lab: Lu) Fast, Versatile, and Quantitative Annotation of Complex Phenotypes

8:00 pm

Amelie Bergs (Lab: Gottschalk) Actuation and Imaging of Excitable Cell Activity Using Microbial Rhodopsins as Genetically Encoded Voltage Sensors

8:15 pm

Heather Hundley (Lab: Hundley) ADARs and A-to-I RNA Editing Regulate Gene Expression in the Nervous System

8:30 – 10:30 pm

Poster Session #1 & Refreshments (ODD number posters present) Great Hall/Reception Room (4th floor) Neural diseases and regeneration (70 – 94) Behavior and Plasticity (95-118) Neural Circuits and Behavior (119 – 174) Neurodevelopment (175 – 202) Sensation (203 – 216) Synaptic function and modulation (217 – 229) Technical advances (230 – 241)

Shannon Hall

Great Hall/Reception Room

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Wednesday, June 27th 7:00 am – 5:00 pm


8:00 am – 9:00 am



9:00 am – 12:30 am Oral Session #5 Shannon Hall Behavior and Plasticity Chairs: Jennifer Garrison (Buck Institute) & Aakanksha Singhvi (Fred Hutchinson Cancer Research Center) 9:00 am

Plenary: Noelle L’Etoile, University of California, San Francisco, USA The Importance of Rest During the Post Training/Learning Period

9:30 am

Michael O’Donnell (Lab: Sengupta) Modulation of Aversive Chemical Responses via Colonization by Tyramine-Producing Bacteria

9:45 am

Alexander Bowitch (Lab: Ferkey) Protein Arginine Methylation Regulation of the C. elegans SER-2 Tyramine Receptor

10:00 am

Jintao Luo (Lab: Portman) PDFR-1 Signaling and Genetic Sex Intersect to Modulate Behavioral Responses to Sex Pheromone

10:15 am

Lisa Voelker Electrical Synapses as Modulators of Neural Activity

10:30 – 10:50 am

Refreshment Break

10:50 am

James Lightfoot (Lab: Sommer) Small Peptide Mediated Self-Recognition Prevents Cannibalism in Predatory Nematodes

11:05 am

Katleen Peymen (Lab: Schoofs) An Evolutionarily Ancient Neuropeptide System Molulates Aversive Gustatory Learning in Caenorhabditis elegans

11:20 am

Eleni Gourgou (Lab: Hsu) C. elegans Learning and Decision Making in T-Shaped Mazes

11:35 am

Siyu Serena Ding (Lab: Brown) Quantitative Phenotyping and Modeling Identifies Key Behavioral Rules Underlying C. elegans Aggregation

(Lab: Bai)

Shannon Hall Lobby

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior 11:50 am

Agnieszka Podraza (Lab: Naredi) Interaction of Oxidized ASNA-1 and ENPL-1(GRP94) in Neurons Promotes Insulin Secretion

12:05 pm

Ava Handley (Lab: Pocock) Neuronal Control of Intestinal Metabolism Through ETS-5-Mediated Insulin Signalling

12:30 – 2:00 pm

Luncheon Buffet

2:00 pm – 5:30 pm

Oral Session #6 Shannon Hall Sensation Chairs: Valeria Vasquez (University of Tennessee Health Science Center) & Maxwell Heiman (Harvard University)

2:00 pm

Plenary: Miriam Goodman, Stanford University, USA The Mechanics and Biophysics of Getting in Touch

2:30 pm

Patrick McClanahan (Lab: Fang-Yen) Shake ‘n Wake: Using Mechanosensory Stimulation to Probe Homeostatic Rebound During Stress-Induced Sleep

2:45 am

Yosuke Ikejiri (Lab: Kimura) Learning-Dependent Neural Gain Control by Asymmetric Modulation of First- and SecondOrder Time-Differential of Stimulus in Sensory Neurons

3:00 pm

Sylvia Fechner (Lab: Goodman) Composition of Native MET Channels Responsible for Gentle Touch Sensation

3:15 pm

Aakankha Singhvi (Lab: Shaham) A Single Glia-Sensory Neuron Pair Interact Through Multiple Molecular Mechanisms

3:30 – 3:50 pm

Refreshment Break

3:50 pm

Plenary: Shawn Xu, University of Michigan, USA Sensation, Circuits and Longevity: Lessons from the Worm

4:20 pm

Mary Rossillo (Lab: Ringstad) A Survey of Terminal Selector Transcriptional Targets Reveals a Novel Signaling Molecule Important for Carbon Dioxide Sensing

4:35 pm

Douglas Reilly (Lab: Srinivasan) Behavioral Valence to a Mating Cue is Regulated by a Neuropeptide

4:50 pm

Astra Bryant (Lab: Hallem) A Critical Role for Thermosensation in Host Seeking by Skin-Penetrating Nematodes

Tripp Commons

Shannon Hall Lobby

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior 5:05 pm

Jaeseok Park (Lab: Kim) cGMP-Dependent Signaling Regulates daf-7 Expression in the ASJ Neurons in Response to Bacterial Metabolites

5:20 pm

Elizabeth Glater (Lab: Glater) Identification of Attractive Odorants Released by Preferred Bacterial Food Found in the Natural Habitats of C. elegans

5:30 – 7:00 pm

Dinner Buffet

8:00 – 10:00 pm

Poster Session #2 & Refreshments (EVEN number posters present) Great Hall/Reception Room (4th floor) Neural diseases and regeneration (70 – 94) Behavior and Plasticity (95-118) Neural Circuits and Behavior (119 – 174) Neurodevelopment (175 – 202) Sensation (203 – 216) Synaptic function and modulation (217 – 229) Technical advances (230 – 241)

10:00 – 12:00 am

Dance

Tripp Commons

Great Hall/Reception Room

Tripp Commons

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Thursday, June 28th 7:00 am – 1:30 pm


8:00 am – 9:00 am



9:00 am – 12:30 pm Oral Session #7 Aging, Neural Diseases and Regeneration Chairs: Dong Yan (Duke University) & Rebecca Taylor (MRC)

Shannon Hall

9:00 am

Plenary: Anne Hart, Brown University, USA Conserved Mechanisms Underlie Sleep and Neurodegeneration

9:30 am

Shaarika Sarasija (Lab: Norman) sel-12 Mutations Deregulate Mitochondrial Ca2+ Homeostasis Causing Oxidative Stress Mediated Neurodegeneration in Caenorhabditis elegans

9:45 am

Danielle Mor (Lab: Murphy) The Role of Branched-Chain Amino Acid Transferase 1 in Parkinson’s Disease, Aging, and Longevity

10:00 am

Piya Ghose (Lab: Shaham) EFF-1 Fusogen Promotes Phagosome Sealing During Cell Process Clearance

10:15 am

Lizhen Chen (Lab: Chen) The Function and Dynamics of Autophagy in C. elegans Axon Regeneration

10:30 – 10:50 am

Refreshment Break

10:50 am

Xue Yan Ho ADM-4 is a Novel Regulator of Axonal Fusion

11:05 am

Lezi E (Lab: Yan) An Epidermal Immune Signaling Network Regulates Antimicrobial Peptide-Mediated Dendrite Degeneration in Aging

11:20 am

Luisa Scott (Lab: Pierce) Small Molecule Modulators of Sig2R/Tmem97 Reduce Alcohol Withdrawal-Induced Behaviors

11:35 am

Rashmi Chandra (Lab: Alcedo) Stress: A Story of Insulin-like Peptides, Message Mobilization, and Survival

11:50 am

Sandra Encalada (Lab: Encalada) Clearance of Circulating Transthyretin Decreases Cell Non-Autonomous Proteotoxicity in Caenorhabditis elegans

Shannon Hall Lobby (Lab: Hilliard)

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12:05 pm

Rebecca Taylor (Lab: Taylor) Understanding the Effects of Inter-Tissue UPR Signalling on Ageing and Proteostasis

12:20pm

Closing remarks, meeting evaluation, passing of the torch

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ORAL & POSTER LIST 1 Nested Neuronal Oscillators Orchestrate Motor Actions Across Timescales Manuel Zimmer, Harris Kaplan, Oriana Salazar Thula 2 Principles of Neural Coding for Efficient Navigation in Gradients Alon Zaslaver, Eyal Itskovits, Rotem Ruach 3 C.elegans Olfactory Neurons Fire Calcium-Mediated All-or-None Action Potentials Qiang Liu, Philip Kidd, May Dobosiewicz, Cori Bargmann 4 A Tyraminergic Feedback-Loop Filters Reafferent Perception of Self-Movement in C. elegans Chemosensation Julia Riedl, Manuel Zimmer 5 The ASICs DEL-7 and DEL-3 Mediate Food Responses in An Enteric Serotonergic Neuron that Drives Persistent Behaviors Steven Flavell, Jeffrey Rhoades, Jessica Nelson, Ijeoma Nwabudike, Daniel Colon-Ramos 6 How Does an Animal Move? An Integrative Model of C. elegans Forward Locomotion Tianqi Xu, Jing Huo, Shuai ShaoMichelle Po, Taizo Kawano, Yangning Lu, Min Wu, Mei Zhen, Quan Wen 7 Excitatory Motor Neurons are Local Oscillators for Reverse Locomotion Shangbang Gao, Sihui Asuka Guan, Anthony D. Fouad, Jun Meng, Taizo Kawano, Yung-Chi Huang, Yi Li, Salvador Alcaire, Wesley Hung, Yangning Lu, Yingchuan Billy Qi, Yishi Jin, Mark J. Alkema, Christopher Fang-Yen, Mei Zhen 8 Live Imaging of the C. elegans Connectome Oliver Hobert, Hang Lu 9 The C. elegans Neuronal Gene Expression Map & Network (CeNGEN) Marc Hammarlund, Oliver Hobert, David Miller, Nenad Sestan 10 Axonal Fusion: An Alternative Mechanism to Repair Injured Axons Massimo A Hilliard 11 An Autism-Causing Mutation Disrupts Axon Termination by Misregulating Lysosome Function Tyler M Buddell, Christopher C Quinn 12 Robo/SAX-3 functions as a Wnt Co-Receptor during Directional Neurite Outgrowth in C. elegans Mei Ding, Jiaming Wang 13 A Transcription Factor Titration Mechanism for the Establishment and Maintenance of Neuron Identity Paschalis Kratsios, Weidong Feng, Pauline Dao 14 WormGUIDES: Assembling and Accessing a Complete, Integrated Record of Neural Development Anthony Santella, Mark Moyle, Ryan Christensen, Kris Barnes, Gabriela Bosque, Leighton Duncan, William Duncan, Li Fan, Brandon Harvey, Richard Ikegami, Braden Katzman, Abhishek Kumar, Nhan Nguyen, Titas Sengupta, Pavak Shah, Doris Tang, Daniel Colón-Ramos, Hari Shroff, William A. Mohler, Zhirong Bao 15 Connecting Genes with Phenotypes for Epilepsy and Neurodegenerative Disease Kat McCormick 16 A Different Kind of Dendrite-Glia Interaction in C. elegans Maxwell G. Heiman, Elizabeth R. Lamkin, Ian G. McLachlan 17 “The creation of dendrites”: Axon-Dependent Dendritic Development and Maintenance in Somatosensory Neurons Nelson Ramirez, Burcu Beyaz, Benjamin Raja,Julius Fredens, Ken Nguyen, Nils J. Færgeman, David H. Hall, Hannes E. Buelow 18 Axonal Tiling in D-Type Motor Neurons Ardalan Hendi, Kota Mizumoto 19 An Update about WormBase Tools Wen Chen 20 Multiple roles of apl-1, the C. elegans human APP orthologue Chris Li 21 Identification of New Ionotropic Receptors For Monoamines and Other Neurotransmitters Iris Hardege, Julia Morud, William R Schafer 22 Bacterial Diet Modulates Cholinergic Signaling through Vitamin B12-Dependent Metabolic Changes in the Intestine Wookyu Kang, Mark J Alkema 23 Regulation of the C. elegans Nicotinic Acetylcholine Receptor ACR-16 is Calcium-Dependent Ashley A. Martin, Janet Richmond 24 Metabotropic and Ionotropic Glutamate Receptors Coordinately Regulate Olfactory Learning in AIB Interneurons Kotaro Kimura, Shuhei Yamazaki, Takeshi Ishihara 25 Enhanced High-Throughput Phenotyping of C. elegans Using the COPAS Vision Flow Cytometer with Imaging Capabilities Mikalai Malinouski 26 Vascular Endothelial Growth Factor (VEGF) Receptor-related VER-1 and VER-4 regulateRGlutamatergic Behavior by Promoting Cell Surface Levels of GLR-1 Glutamate receptors Peter Juo, Eric Luth, Carmino Riccio, Julia Hofer, Kaitlin Markoja 27 Neuromedin U Signaling in Experience-Dependent Salt Chemotaxis Jan Watteyne, Petrus Van der Auwera, Clare Foley, Katleen Peymen, Liliane Schoofs, Isabel Beets 28 Slowpoke, Where'd You Go? Timothy Cheung, Kelly Oh, Hongkyun Kim 29 Modulation of the NCA Ion Channels by Dopamine, GRK-2, and ERK Signaling Irini Topalidou, Brantley Coleman, Michael Ailion 30 Chemical and Electrical Synapses Cooperate in a Circuit Motif for Sensory Integration May Dobosiewicz, Cori Bargmann

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior 31 Serotonin Disinhibits the ASH Nociceptive Neurons by Suppressing Ca2+-Dependent Negative Feedback Bruce Bamber,Paul David Edward Williams 32 Nematode Research Technology: The Future is Simple Shawn Lockery 33 The Development of a Synthetic Neurotransmission System Navin Pokala 34 Fast, Versatile, and Quantitative Annotation of Complex Phenotypes Kathleen E Bates, Shen Jiang, Hang Lu 35 Actuation and Imaging of Excitable Cell Activity using Microbial Rhodopsins as Genetically Encoded Voltage Sensors Amelie Bergs, Negin AzimiHashemi, Rebecca Scheiwe, Wagner Steuer Costa, Jana F. Liewald, Alexander Gottschalk 36 ADARs and A-to-I RNA Editing Regulate Gene Expression in the Nervous System Heather Hundley, Sarah Deffit, Brian Yee, Aidan Manning, Suba Rajendren, Pranathi Vadlamani, Emily Wheeler, Alan Domissy, Michael Washburn, Gene Yeo 37 The Importance of Rest During the Post Training/ Learning Period Noelle L'etoile 38 Modulation of Aversive Chemical Responses via Colonization by Tyramine-Producing Bacteria Michael O'Donnell, Pin-Hao Chao, Piali Sengupta 39 Protein Arginine Methylation Regulation of the C. elegans SER-2 Tyramine Receptor Alexander Bowitch, Kerry L. Michaels, Michael C. Yu, Denise M. Ferkey 40 PDFR-1 Signaling and Genetic Sex Intersect to Modulate Behavioral Responses to Sex Pheromone Jintao Luo, Kelli A. Fagan, Douglas S. Portman 41 Electrical Synapses as Modulators of Neural Activity Lisa Voelker, Ithai Rabinowitch, Jihong Bai 42 Small Peptide Mediated Self-Recognition Prevents Cannibalism in Predatory Nematodes James W Lightfoot, Martin Wilecki, Ralf J Sommer 43 An Evolutionarily Ancient Neuropeptide System Molulates Aversive Gustatory Learning in Caenorhabditis elegans Katleen Peymen, Jan Watteyne, Elien Van Sinay, Isabel Beets, Liliane Schoofs 44 C. elegans learning and decision making in T-shaped mazes Eleni Gourgou, Kavya Adiga, Ao-Lin Allen Hsu 45 Quantitative Phenotyping and Modeling Identifies Key Behavioral Rules Underlying C. elegans Aggregation Siyu Serena Ding, Linus J Schumacher, Robert G Endres, Andre EX Brown 46 Interaction of Oxidized ASNA-1 and ENPL-1(GRP94) in Neurons Promotes Insulin Secretion Agnieszka Podraza, Balasubramanian Natarajan, Dorota Robakowska, Gautam Kao, Peter Naredi 47 Neuronal Control of Intestinal Metabolism Through ETS-5-Mediated Insulin Signaling Ava Handley, Roger Pocock 48 The Mechanics and Biophysics of Getting in Touch Miriam Goodman 49 Shake ‘n Wake: Using Mechanosensory Stimulation to Probe Homeostatic Rebound during Stress-Induced Sleep Patrick McClanahan, Ben Habermeyer, Joyce Xu, Anthony Ma, Christopher Fang-Yen 50 Learning-Dependent Neural Gain Control by Asymmetric Modulation of First- and Second-Order Time-Differential of Stimulus in Sensory Neurons Yosuke Ikejiri, Yuki Tanimoto, Shuhei Yamazaki, Kosuke Fujita, Kotaro Kimura 51 Composition of Native Met Channels Responsible for Gentle Touch Sensation Sylvia Fechner, LingXin Wang, Frederic Loizeau, Adam L Nekimken, Isabel D’Alessandro, Beth L Pruitt, Miriam B Goodman 52 A Single Glia-Sensory Neuron Pair Interact through Multiple Molecular Mechanisms Aakanksha Singhvi, Shai Shaham 53 Sensation, Circuits and Longevity: Lessons from the Worm Shawn Xu 54 Using Terminal Selector Transcriptional Targets and Differential Transcriptome Analysis to Identify Novel Regulators of Carbon Dioxide Sensing Mary Rossillo, Niels Ringstad 55 Behavioral Valence to a Mating Cue is Regulated by a Neuropeptide Douglas K Reilly, Emily J McGlame, Haylea T Northcott, Jagan Srinivasan 56 A Critical Role for Thermosensation in Host Seeking by Skin-Penetrating Nematodes Astra S. Bryant, Felicitas Ruiz, Spencer S. Gang, Michelle L. Castelletto, Jacqueline B. Lopez, Elissa A. Hallem 57 cGMP-Dependent Signaling Regulates daf-7 Expression in the ASJ Neurons in Response to Bacterial Metabolites Jaeseok Park, Joshua D. Meisel, Dennis H. Kim 58 Identification of Attractive Odorants Released by Preferred Bacterial Food Found in the Natural Habitats of C. elegans Elizabeth E. Glater, Soleil E. Worthy, Lillian Haynes, Melissa Chambers, Danika Bethune, Emily Kan, Kevin Chung, Ryan Ota, Charles J. Taylor 59 Conserved Mechanisms Underlie Sleep and Neurodegeneration Anne Hart 60 sel-12 Mutations Deregulate Mitochondrial Ca2+ Homeostasis Causing Oxidative Stress Mediated Neurodegeneration in Caenorhabditis elegans Shaarika Sarasija, Kenneth R. Norman 61 The Role of Branched-Chain Amino Acid Transferase 1 in Parkinson’s Disease, Aging, and Longevity Danielle E. Mor, Rachel Kaletsky, Will Keyes, Salman Sohrabi, Coleen T. Murphy 62 EFF-1 Fusogen Promotes Phagosome Sealing During Cell Process Clearance Piya Ghose, Alina Rashid, Peter Insley, Anupriya Singhal, Meera Trivedi, Pavak Shah, Yun Lu, Zhirong Bao, Shai Shaham 63 The Function and Dynamics of Autophagy in C.elegans Axon Regeneration Lizhen Chen, Su Hyuk Ko 64 ADM-4 is a Novel Regulator of Axonal Fusion Xue Yan Ho, Sean Coakley, Massimo A. Hilliard

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior 65 An Epidermal Immune Signaling Network Regulates Antimicrobial Peptide-Mediated Dendrite Degeneration in Aging Lezi E, Ting Zhou, Sehwon Koh, Marian Chuang, Ruchira Sharma, Nathalie Pujol, Andrew Chisholm, Cagla Eroglu, Hiroaki Matsunami, Dong Yan 66 Small Molecule Modulators of sig2R/Tmem97 Reduce Alcohol Withdrawal-Induced Behaviors Luisa L Scott, James Sahn, Antonio Ferragud, Rachel Yen, Praveen Satarasinghe, Michael Wood, Timothy Hodges, Ted Shi, Brooke Prakash, Kaitlyn Friese, Angela Shen, Valentina Sabino, Stephen Martin, Jonathan Pierce 67 Stress: A Story of Insulin-Like Peptides, Message Mobilization, and Survival Rashmi Chandra, Lisa Li, Zahabiya Husain, Shashwat Mishra, Joy Alcedo 68 Clearance of Circulating Transthyretin Decreases Cell Non-Autonomous Proteotoxicity in Caenorhabditis elegans Kayalvizhi Madhivanan, Erin Greiner, Miguel Alves-Ferreira, Nirvan Rouzbeh, Carlos Aguirre, Johan Paulsson, Justin Chapman, Xin Jiang, Felicia Ooi, Carolina Lemos, Andrew Dillin, Veena Prahlad, Jeffery Kelly 69 Understanding the Effects of Inter-Tissue UPR Signalling on Ageing and Proteostasis Rebecca Taylor, Soudabeh Imanikia, Ming Sheng, Nesem Ozbey P70 No Abstract Assigned P71 Acute-Stress Impairs Cytoprotective Mechanisms through Neural Inhibition of the Insulin Pathway Diego Rayes, Maria Jose De Rosa, Tania Veuthey, Jeremy Florman, Jeff Grant, Gabriela Blanco, Mark Alkema, Natalia Anderson, Jamie Donnelly P72 An Integrated Non-Vertebrate Drug Discovery Platform for Neurodegenerative Disease Karolina Chocian, Nicolas Dallière, Thomas Barratt, Hannah Rhodes, Julia Sherriff, Pete Appleford, Alison Woollard P73 Stress Leads to Neurodegeneration in Single-Copy Models of Amyotrophic Lateral Sclerosis in C. elegans Saba N. Baskoylu, Katherine Yanagi, Jill Yersak, Patrick O'Hern, Loraina Stinson, Sarah Grosser, Animesh Mahapatra, Jeremy Lins, Kelsey Schuch, Anne C. Hart P74 Neuronal Somas Suffice for Morphofunctional Regeneration during Diapause in C. elegans Mauricio Caneo, Mark Alkema, Andrea Calixto P75 Possible Role of Tamalin/GRAS-1 in Bridging Glutamate & Insulin/IGF Signaling (IIS) Cascades in a Nematode Model of Excitotoxic Necrosis Ayesha Chowdhury, Shavanie Pershad, Teena Thomas, Itzhak Mano P76 Functional Study of Huntingtin using Caenorhabditis eleagans Christine Chung, Hanee Lee, Ihn Sik Seong, Junho Lee P77 Identification of Genetic Suppressors of smn-1 in Neurodegeneration Elia Di Schiavi, Pamela Santonicola, Ivan Gallotta, Alessandro Esposito, Giuseppina Zampi P78 Food Perception through a Pair of Olfactory Neurons Triggers Rewiring of Organismal Proteostasis Fabian Finger, Franziska Ottens, Alexander Springhorn, Tanja Drexel, Lucie Proksch, Sophia Metz, Luisa Cochella, Thorsten Hoppe P79 The Role of MANF in ER Stress Response in C. elegans Jessica Hartman, Christopher Richie, Priscila Castillo, April Zhu, Yun Wang, Barry Hoffer, Joel Meyer, Brandon Harvey P80 Lipid Droplets in Neuron: Roles and Regulation Xun Huang, Leilei Yang, Jinlin Zhu P81 C. elegans as a Neurological Model for Duchenne Muscular Dystrophy Kiley Hughes, Anjelica Rodriguez, Kevin Tragresser, Joseph Schweickert, Alexander Kullman P82 The Worm Observatory: A System for High-Throughput Behavioral Analysis Rex Kerr, Cynthia Kenyon P83 Retrograde Transport and ATG-4.2-Mediated Maturation Cooperate to Remove Autophagosomes from the Synapse Mia D. Krout, Sarah E. Hill, Janet E. Richmond, Daniel A. Colón-Ramos P84 Novel Roles of the Hippo Pathway in Structural Maintenance of C. elegans Neurons: A Genetic Model of Premature Aging-Related Neurodegeneration Hanee Lee, Junsu Kang, Junho Lee P85 A Functional Study of ALS associated variants using a CRISPR-Cas9 Approach Lauren Macconnachie, Asim Beg P86 Putative Synergistic Effects of CRH-1/CREB and DAF-16/FOXO Mediated Regulation of Neuroprotective Programs in a Nematode Model of Excitotoxic Necrosis Zelda Zara Mendelowitz, K. Genevieve Feldmann, Ayesha Chowdhury, Itzhak Mano P87 Deciphering Autism Spectrum Disorder (ASD)-Associated Variants of Uncertain Significance in Human PTEN Catharine H. Rankin, Troy A. McDiarmid, Kathryn Post, Riki Dingwall, Payel Ganguly, Matthew Edwards, Vinci Au, Ben Callaghan, Manuel Belmadani, Fabian Meili, Warren Meyers, Barry Young, Sanja Rojic, Chris Loewen, Douglas Allan, Timothy O'Connor, Shernaz Bamji, Paul Pavlidis, Kurt Haas P88 slc-25a46 is Required for Proper Localization of Mitochondria and Mitochondrial Fusion Hiroyuki Obinata, Asako Sugimoto, Shinsuke Niwa P89 Food Perception through a Pair of Olfactory Neurons Triggers Rewiring of Organismal Proteostasis Fabian Finger, Franziska Ottens, Alexander Springhorn, Tanja Drexel, Lucie Proksch, Sophia Metz, Luisa Cochella, Thorsten Hoppe P90 Cell Specific Roles of sel-12 in Chemotaxis and Neurodegeneration Mahraz Parvand, Tahereh Bozorgmehr, Catharine Rankin P91 σ2R/TMEM97 Ligands are Neuroprotective in a C. elegans Model of APP/APOE4-related Neurodegeneration Ted Shi, Luisa L. Scott, James J. Sahn, Wisath Sae-Lee, Michael D. Wood, Jonathan T. Pierce, Stephen F. Martin P92 Forever Young – Lactate and Pyruvate Delay Aging Related Phenotypes in C. elegans A. Tauffenberger, P. Magistretti, L. Mottier, H. Fiumelli P93 Cell Non-Autonomous Regulation of Proteostasis- Deciphering the Neuron-to-Gut Axis Kavya Leo Vakkayil, Alexandra Segref, Thorsten Hoppe P94 A Role for Neural Gap Junctions in Regulating Ageing Nathalie A. Vladis, Karl Emanuel Busch P95 SOD-1 Mediates Pathogen Avoidance Behavior in C. elegans Alexander Horspool, Howard Chang P96 Sex Differences in C. elegans Aversive Behavior Aditi H Chaubey, Ronald A Bola, Noah Reger, Douglas S. Portman, Denise M. Ferkey

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior P97 Temporal Processing and Chemotactic Behavior in C. elegans Olfactory Learning Kevin Chen, Alicia L. Castillo, Mochi Liu, Andrew M. Leifer P98 Caenorhabditis elegans Alters Mating Strategies by Modulating Pheromone Valence Sarah E. Hall, Rose Al-Saadi, Jintao Luo, Douglas S. Portman P99 An Analysis of the Regulatory Mechanisms of Learning through the DAG/PKC Pathway in the Nematode C. elegans Shingo Hiroki, Shigehiro Tamura, Hirofumi Kunitomo, Masahiro Tomioka, Yuichi Iino P100 C. elegans can Learn to Modulate its Feeding Behavior by Associating a Noxious Stimulus with Odor Eugene L.Q. Lee, H. Robert Horvitz P101 Investigating the Molecular Mechanisms of C. elegans Thermal Preference Joon Lee, Agustin Almoril-Porras, Daniel Colón-Ramos, Josh Hawk P102 Dissecting Nociceptive Habituation in C. elegans using St-LiTe: A Versatile Stimulation Platform for Light and Temperature Andrei-Stefan Lia, Aurore Jordan, Filipe Marques, Dominique A. Glauser P103 Interstimulus Iterval-Dependent Effects of the Glutamate Gated Chloride Channel avr-14 on Habituation are Eliminated by Optogenetic Stimulation of Mechanosensory Neurons Jan Ho (Joseph) Liang, Troy McDiarmid, Stephan Steidl, Catharine Rankin P104 High-Throughput Phenomic Characterization of Autism Spectrum Disorder-Associated Genes Reveals a Functional Gene Network Underlying Hypersensitivity and Impaired Habituation Troy A. Mcdiarmid, Manuel Belmadani, Fabian Meili, Kurt Haas, Paul Pavlidis, Catharine Rankin P105 The Role of DAF-16/FOXO in the ASER Sensory Neuron in Taste Avoidance Learning Takashi Nagashima, Masahiro Tomioka, Yuichi Iino P106 Inherited Small RNAs Regulate Chemotaxis Behavior in a Stressful Environment in C. elegans Rachel Posner, Ekaterina Star, Sarit Anava, Eran Azmon, Shahar Bracha, Hila Gingold, Oded Rechavi P107 Long-Term Behavioral and Neural Circuit Adaptations to Early Life Stress Sreeparna Pradhan, Michael Hendricks P108 Analyses of Chemosensory Responses in dauer larvae using High-Resolution Behavioral Assays and Calcium Imaging Travis Rogers, Michael O'Donnell, Piali Sengupta P109 The Novel F-box Protein Regulates a Quick Avoidance Behavior to a Pathogenic Bacteria P. aeruginosa in C. elegans Ryuichi Saito, Youichi Shinkai, Motomichi Doi P110 Afferent and Efferent Neuropeptide Systems Involved in Arousal William Schafer, Yee Lian Chew, Yoshinori Tanizawa, Yongmin Cho, Buyun Zhao, Alex Yu, Laura Grundy, Evan Ardiel, Catherine Rankin, Hang Lu, Isabel Beets P111 The C. elegans Pharyngeal Grinder Undergoes Complex Extracellular Remodeling During Developmentally Timed Sleep Alessandro P. Sparacio, Matthew D. Nelson, Karen Snetselaar, David M. Raizen, David H. Hall P112 Neural and Molecular Basis Involved in Low Preference to Bifidobacterium infantis in Caenorhabditis elegans Simo Sun, Yoshikazu Nishikawa, Eriko Kage-Nakadai P113 Molecular and Neuronal Mechanisms Mediating Starvation-Dependent Thermosensory Behavioral Plasticity Asuka Takeishi, Piali Sengupta P114 Exploring the Role of CLHM-1 in Extracellular Vesicles and Behavior Denis Touroutine, Michael Clupper, Matthew Hudson, Jessica Tanis P115 Sensory Orientation in the Nematode Caenorhabditis elegans Reflects the Physical Nature of the Stimulus Andres Vidal-Gadea, Chance Bainbridge, Zachary Benefield, Wolfgang Stein P116 Temporal and Spatial Factors that Influence Magnetotaxis in C. elegans Andres Vidal-Gadea, Carlos Caldart, Chance Bainbridge, Benjamin Clites, Bridgitte Palacios, Layla Bakhtiari, Vernita Gordon, Diego Golombek, Jonathan Pierce P117 A Male-Specific Neuroendocrine Feedback Loop Balances the Prioritization of Mate Searching vs Feeding Emily R Wexler, Douglas Portman P118 Genome-Wide Association Study Reveals a QTL for Hitchhiking Behavior in C. elegans Heeseung Yan, Daehan Lee, Heekyeong Kim, Young-ki Paik, Erik C. Andersen, Junho Lee P119 EphR/ephrin Impact on Food-Seeking Behavior through Genetic Dissection of the Thermosensory/Chemosensory Neuronal Circuit Miranda Arnold, Tyler Hill, Ashtyn Johnston, Brian Ackley, Martin Hudson P120 Neural Pre-Conditioning Underlying Oxygen Deprivation In C. elegans Heather L. Bennett, Robert G. Kalb P121 The Orcokinin Neuropeptide NLP-14 Regulates Stress-Induced Sleep Kristen Buscemi, Niknaz Riazati, Natalie Barrett, Matthew Nelson P122 A Family of Receptors that Activate the Egg-Laying Circuit in Response to Serotonin and Neuropeptides Co-Released by the HSN Neuron Andrew Olson, Allison Butt, Robert Fernandez, Jacob Brewer, Isabel Beets, Liliane Schoofs, Michael Koelle P123 Characterizing Calcium Activity of Single AIY Interneurons in Freely Moving C. elegans Navigating a Thermal Gradient Ernesto Cabezas-Bou, Josh Hawk, Agustín Almoril-Porras, Ifedayo-Emmanuel Adeyefa-Olasupo, Manuel Díaz-Ríos, Daniel Colón-Ramos P124 A Novel Two-Tier Mechanism of Glutamate Clearance in the Glia-Deprived C. elegans Synaptic Hub Joyce Chan, KyungWha Lee, Jenny Wong, Itzhak Mano P125 Two Newly-Identified Neural Branches May Explain How C. elegans Egg-Laying Circuit Activity is Regulated Nakeirah T.M. Christie, Kimberly Wei, Robert Fernandez, Michael Koelle P126 Elucidating the Complex Genetics of Acute Ethanol Intoxication in C. elegans Benjamin L. Clites, Bridgitte Palacios, Erik Andersen, Jonathan Pierce P127 The C. elegans Egg-Laying Circuit is Activated during Mating Behavior Kevin Collins, Michael Scheetz, Layla Nassar P128 Homeostatic Feedback, Not Early Activity, Modulates the Development of Two-State Patterned Activity in the C. elegans Egg-Laying Behavior Circuit Kevin Collins, Bhavya Ravi P129 Beauty Sleep: Cuticle Collagen Genes Regulate Sleep in Response to Cell Stress in C. elegans Kristen C. Davis, David M. Raizen

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior P130 Inhibitory Phase Reset Supports Rapid Locomotion Lan Deng, Lianhua Jin, Jack E. Denham, Omer Yuval, Thomas Ranner, Netta Cohen, Gal Haspel P131 Understanding how Gαq Signaling Modulates Egg-Laying Circuit Activity and Behavior of C. elegans Pravat Dhakal, Kevin M. Collins P132 Thermal Microsurgery with a Pulsed Infrared Laser Reveals Multiple Origins of Convulsions in acr-2(gf) Mutants Alice Liu, Anthony Fouad, Angelica Du, Priya Bhirgoo, Julian Mark, Shelly Teng, Bowen Yao, Hongfei Ji, Christopher Fang-Yen P133 Phase Response Curves for Optogenetic Manipulation during Forward Locomotion Support a Threshold Model for Rhythm Generation Anthony Fouad, Pilar Alvarez-Illera, Shelly Teng, Hongfei Ji, Bowen Yao, Christopher Fang-Yen P134 Multiple Sensory Inputs Modulate a Short-Lived Sleep-Like State in C. elegans Daniel Gonzales, Jasmine Zhou, Jacob Robinson P135 Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network Alexandra Oranth, Christian Schultheis, Oleg Tolstenkov, Karen Erbguth, Jatin Nagpal, David Hain, Sebastian Wabnig, Wagner Steuer Costa, Rebecca McWhirter, Sven Zels, David Miller III, Isabel Beets, Alexander Gottschalk P136 Transgenerational Effects of Alcohol Exposure in C. elegans Dawn M. Guzman, Dylan Sucich, Keerthana Chakka, Vishy R. Iyer, Jonathan T. Pierce P137 Unraveling the Role of Somatostatin-like System in C. elegans Ilayda Hasakiogullari, Sven Zels, Katleen Peymen, Melissa Fadda, Jan Watteyne, Elke Vandewyer, Isabel Beets, Liliane Schoofs P138 The Role of AFD Gap Junctions in C. elegans Magnetotaxis Behavior Ploy Freebairn, Brenda D. Houck P139 Sleep Enhances Survival from Viral Infection in C. elegans Michael J. Iannacone, Paul Um, David M. Raizen P140 Robustness Analysis on Synaptic Structure and Causality Analysis on Whole-Brain Imaging Data Yuishi Iwasaki, Hirofumi Sato, Suzu Oe, Sayuri Kuge, Takayuki Teramoto, Terumasa Tokunaga, Osamu Hirose, Stephen Wu, Yu Toyoshima, Moon-Sun Jang, Ryo Yoshida, Yuichi Iino, Takeshi Ishihara P141 Integrating Stretch-Receptor Feedback and Multiple Intrinsic Oscillators in a Model of Forward Locomotion Eduardo J. Izquierdo, Erick Olivares, Randall D. Beer P142 Phase Response Analysis of the C. elegans Motor Circuit Under Optogenetic Inhibition using a Coupled-Oscillator Model Hongfei Ji, Anthony Fouad, Bowen Yao, Christopher Fang-Yen P143 Decoding Head Neural Circuit Underlying Rhythmic Forward Movement in C. elegans Jinmahn Kim, Jihye Yeon, Gheon-Gyu Park, Byung-Chang Suh, Jongrae Kim, Kyuhyung Kim P144 Dissecting the Function of the Cholinergic VC Motor Neurons in C. elegans Egg-Laying Behavior Richard Kopchock III, Kevin M Collins P145 The Endocannabinoid AEA Amplifies Food Preferences in C. elegans Anastasia Levichev-Connolly, Serge Faumont, Rachel Berner, Shawn Lockery P146 Temporal Processing and Context Dependency in C. elegans Mechanosensation Mochi Liu, Anuj Sharma, Joshua Shaevitz, Andrew Leifer P147 The SIK Homologue KIN-29 Regulates Sleep and Energy Metabolism Lindsey E Lopes, Jeremy Grubbs, Alexander van der Linden, David Raizen P148 How Asymmetric Motor Circuit Generates Symmetrical Motor Output Yangning Lu, Asuka Guan, Daniel Witvliet, Ben Mulcahy, Jin Meng, Sway Chen, Jun Meng, Quan Wen, Aravinthan Samuel, Mei Zhen P149 Understanding how the Interneuron AIY Mediates Salt Concentration Memory-Dependent Behavior in C. elegans Llian Mabardi, Hirofumi Kunitomo, Hirofumi Sato, Yuichi Iino P150 Adenosine Receptor Signaling and Recovery Sleep in C. elegans Belinda Mahama, Anne C. Hart P151 Forward Optogenetics: A New Pipeline to Screen for Nociception Genes in C. elegans Filipe Marques, Dominique Glauser P152 Building a Plausible Model for TDP-43 Driven ALS/FTD Pathology Jose L. Martinez, Brittany Flores, Xingli Li, Sami Barmada, Asim Beg P153 Mechanosensory Feedback Regulates Egg-Laying Circuit Activity and Behavior Emmanuel Medrano, Kevin Collins P154 No Abstract Assigned P155 Dopamine Neurons Play a Pivotal Role in Encoding of Short Term Adaptive Memory in Caenorhabditis elegans Vishnu Raj, Anoopkumar Thekkuveettil P156 A Mathematical Framework for Functional Connectivity in C. elegans Francesco Randi, Andrew Leifer P157 Nested Neuronal Oscillators Orchestrate Motor Actions Across Timescales Oriana Salazar Thula, Harris Kaplan, Manuel Zimmer P158 Spitting and Gulping: Opposite Feeding Behaviors Produced by the Graded Activity of a Single Pharyngeal Neuron Steve Sando, Eugene L.Q. Lee, Bob Horvitz P159 Neural Dynamics of Experience-Dependent Gustatory Behavior Hirofumi Sato, Hirofumi Kunitomo, Xianfeng Fei, Koichi Hashimoto, Yuichi Iino P160 Stressful Sleep Christopher F. Saul, Mary Dougherty, Matthew D. Nelson, Jennifer C. Tudor P161 Dissecting the Structure of Foraging Decisions Through Lawn-Leaving Behavior Elias Scheer, Cori Bargmann P162 Predicting Animal Behavior from Neural Dynamics Monika Scholz, Ashley N Linder, Anuj K Sharma, Xinwei Yu, Francesco Randi, Joshua Shaevitz, Andrew M Leifer P163 Neuromuscular Degeneration in the Parasitic Nematode Heterodera glycines Nathan Schroeder, Ziduan Han, Sita Thapa, Ursula Reuter-Carlson, Michael K. Gates, Hannah Reed, Kris N. Lambert P164 Determining Molecular Pathways Involved in Regulating C. elegans Quiescent Behavior in Liquid Kelsey N. Schuch, Saba Baskoylu, Yuliang Guo, Lakshmi N. Govindarajan, Thomas Serre, Anne C. Hart

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior P165 Toxicity Studies of the Dopaminergic System in Caenorhabditis elegans Latasha L. Smith, Ian T. Ryde, Joel N. Meyer P166 Investigating the Effects of Co-Transmission from an Interneuron on the C. elegans Foraging Circuit Aylesse Sordillo, Alejandro Lopez, Cori Bargmann P167 Deciphering Gut-to-Brain Signals in C. elegans Shubhi Srivastava P168 MCTP a Neuronal Protein Regulating Rhythmic Locomotion in Caenorhabditis elegans Jose Luis Tellez Arreola, Ataulfo Martínez Torres P169 Determining the Function of the Globin Gene glb-28 in Sensory Neurons Kumar Tiger, Juan Wang, Maureen Barr P170 Bio-Image Informatics for Whole-Brain Activity Imaging of C. elegans Yu Toyoshima, Stephen Wu, Terumasa Tokunaga, Osamu Hirose, Manami Kanamori, Takayuki Teramoto, Moon-Sun Jang, Hirofumi Sato, Suzu Oe, Yuko Murakami, Ken Sato, Sayuri Kuge, Takeshi Ishihara, Ryo Yoshida, Yuichi Iino P171 Elucidation of Molecular Mechanisms that Underlie Neural Circuit Formation Miri VanHoven, Fatima Farah, Aruna Varshney, Kelli Benedetti, Katie Watters, Raakhee Shankar, David Tatarakis, Doris Coto Villa, Khristina Magallanes, Venia Agenor, William Wung, Nebat Ali, Nghi Le, Jacqueline Pyle, Amber Farooqi, Zanett Kieu, Martina Bremer P172 Robust and Flexible Motor Control during C. elegans Avoidance Behavior Yuan Wang, Xiaoqian Zhang, Qi Xin, Yu Xie, Fan Gao, Mark Alkema, Mei Zhen, Quan Wen P173 Male Neural Dynamics and Behavior Response to Hermaphrodite Sensory Cues Xinwei Yu, Monika Scholz, Anuj K. Shabrma, Francesco Randi, Mochi Liu, Andrew M. Leifer P174 Exploring Sensory Pathways and Behaviors in Filarial Nematode Parasites Nicolas Wheeler, Troy Meikle, Divyaa Srinivasan, Lyric Bartholomay, Mostafa Zamanian P175 Investigating Molecular Mechanisms Underlying Synaptic Remodeling in the C. elegans Motor Circuit Kellianne Alexander, Devyn Oliver, Alison Philbrook, Christopher Lambert, Andrea Thackeray, Maria Doitsidou, Claire Bénard, Micheal Francis P176 Dendrite Morphology under Well-Fed and Starvation Conditions: A Comparison Between FLP and IL2 Arbors Rebecca J Androwski, Janet Goelzer, Cassandra Smith, Nathan E Schroeder P177 Using RNA-Seq to Identify Downstream Targets of the Basic Helix-Loop-Helix Transcription Factor CND-1 Wendy Aquino Nunez, Zachary Mielko, Derrica McCalla, Ciara Hosea, Martin Hudson P178 C. elegans Adult Males Lacking hlh-3 Function Show Altered daf-7 Expression in the ASJ Neurons Kimberly Atteberry, Maryam Sabir, Aixa Alfonso P179 Probing the Scaffolding Effect of the C. elegans Pharynx on Nerve Ring Axons using a Directed Reverse Genetic Screen Kristopher Barnes, Yichi Xu, Rachna Sheth, Zhirong Bao P180 Investigating the Basic Helix-Loop-Helix Transcription Factor NGN-1 during Embryogenesis and Neural Development Elyse Christensen, Alexandra Beasley, Ben Crews, Omar Daouk, Jessica Radchuk, Martin Hudson P181 Visualizing Pharyngeal Circuit Development Steven Cook, David Hall, Oliver Hobert P182 A Novel Role for Notch in Mechanosensory Neuron Connectivity in C. elegans Rachid El Bejjani, Quin Brown, Richard Guerrero P183 A Role for Wnt-β-Catenin Signaling in Positioning Motor Neuorons Along the VNC Justin Evans, Jeffrey Hung , Tony Roenspoes, Antonio Colavita P184 Investigation of the Cellular Mechanism of a Novel Form of Neurite Outgrowth in C. elegans Michael Galiano, Kris Barnes, Li Fan, Anthony Santella, Pavak K. Shah, Braden Katzman, Zhirong Bao P185 The Subcellular Localization Of Proteins That Regulate Mechanosensory Dendrite Termination And Refinement Maria E Gallegos, Cindy Tantilert, Pranti Das, Joshua Azevedo, Darlene Decena, Lorrayne Serra P186 A Small Molecule Screen to Discover Modifiers of PMM-2 Deficiency, a Congenital Glycosylation Disorder, in Nematodes Sangeetha Iyer, Zach Parton, Hillary Tsang, Kausalya Murthy, Ethan Perlstein P187 Hox Transcription Factors Regulate Male Ventral Cord Neuron Identity Andrea K Kalis, Ami Ballmer, Taylor Olin, Andrew Wheeler, Jennifer MR Wolff P188 The Role of Histone Modifications in Shaping Post-mitotic Neuronal Identity Yinan Li, Paschalis Kratsios P189 MAX-1 inhibits UNC-5 activity in regulation of VD Growth Cone Protrusion Snehal Mahadik, Erik Lundquist P190 The Q Neuroblast Transcriptome Reveals Novel Transcription Factors Involved in Q Descendant Migration Sierra Mortimer, Matthew Ochs, Rebecca McWhirter, David Miller, Erik Lundquist P191 The Presumptive RNA-Binding Molecule ETR-1 Interacts with Wnt Signaling in the Guided Migration of the Q Cell Descendants Matthew Ochs, Erik Lundquist P192 Structural and Molecular Analysis of a Novel Model of Dendritic Spines in C. elegans Devyn Oliver, Alison Philbrook, Ken C. Q. Nguyen, David H. Hall, Maria Doitsidou, Claire Bénard, Michael Francis P193 VCs Require HLH-3 Function to Assume their Terminal Differentiation State Lillian Perez, Aixa Alfonso P194 Neurexin Directs Partner-Specific Connectivity in C. elegans Alison Philbrook, Shankar Ramachandran, Christopher Lambert, Devyn Oliver, Michele Lemons, Michael M. Francis P195 Elucidating Interacting Factors of Leukocyte Cell-Derived Chemotaxin 2 (lect-2) in Dendritogenesis Maisha Rahman, Carlos A. Diaz-Balzac, Hannes E. Buelow P196 Systematic Exploration of Early Nervous System Development in C. elegans Alina Rashid, Shai Shaham P197 Characterization of a Putative Rab GTPase in PVD Development Christopher J Salazar, Carlos A Diaz-Balzac, Barth D Grant, Hannes E Bülow P198 How Biological Sex and Neuronal Activity Alter Glia: An Investigation in the Lab and in the Classroom Taralyn M. Tan, Maxwell G. Heiman

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior P199 Characterizing Novel Pathways for Neuronal Tiling in C. elegans Meera Trivedi, Hannes Buelow, Lourdes A. Martin Hernandez P200 Analysis of Syndecan Function at the C.elegans Neuromuscular Junction Camille Vachon, Mélissa Cizeron, Leo Tang, Hannes Bülow, Jean-Louis Bessereau P201 mab-9, a T-box Transcription Factor, is Required for Synaptic Tiling Jane Wang, Kota Mizumoto P202 ATAC-ing Chromatin Accessibility in Neurons Callista Yee, Haley Amemiya, Alan Boyle, Kang Shen P203 Long-Term Sensory Neuron and Behavioral Adaptations in Response to Oxygen Require CREB Jesse A. Cohn, Elizabeth R Lamkin, Max G Heiman, Jonathan T Pierce P204 Analysis of the Controlled Subcellular Localization of CMK-1 in C. elegans Nociceptor Neurons upon Thermal Habituation Domenica Ippolito, Lola Hostettler, Dominique A. Glauser P205 Functional Characterization of C. elegans Piezo Mechanosensitive Channel, pezo-1 Jonathan RM Millet, Rebeca Caires, Valeria Vásquez P206 Touch-Evoked Mechanical Strain in C. elegans Sensory Neurons Adam Nekimken, Miriam Goodman, Beth Pruitt P207 Role of a NEK-Like Kinase in Ciliary Structure and Development Katlin Power, Robert O'Hagan, Amanda Gu, Yasmin Ramadan, Sebastian Bellotti, Maggie Morash, Winnie Zhang, Andy Golden, Harold Smith, Maureen Barr P208 C. elegans AMsh glia engulf AFD Sensory Neuron-Endings Stephan Raiders, Andrea Bae, Shai Shaham, Aakanksha Singhvi P209 Barometric Pressure Changes Induce Temperature-Sensitive Responses in C. elegans Alexandra R. LaHaie, Adam J. Iliff, Elizabeth A. Ronan, Bonnie Zeng, X.Z. Shawn Xu P210 Neural and Genetic Mechanisms of Menthol Sensation in C. elegans Elizabeth A. Ronan, Alexandra R. LaHaie, Erkina Sartbaeva, Mustafa Sami, X.Z. Shawn Xu P211 Characterization of Calcium Signaling and Habituation in the FLP Thermosensory Neurons Gabriella Saro, Filipe Marques, Dominique Glauser P212 GCY-22 Acts in Salt-Sensing Signaling Pathway at the Tip of the ASER Neuron Cilium Servaas van der Burght, Suzanne Rademakers, Jacque-Lynne Johnson, Michel Leroux, Gert Jansen P213 Chemotaxis to NaCl involves the Epithelial Sodium Channel Subunit del-6 Servaas van der Burght, Oluwatoroti Umuerri, Gert Jansen P214 Glial Monitoring of Sensory Neuronal Receptive Endings Katherine Varandas, Yupu Liang, Shai Shaham P215 Using an EGFP based cGMP Sensor to Investigate how the Spatiotemporal Regulation of cGMP Contributes to Sensation and Plasticity in Neurons Sarah Woldemariam, Mary Bethke, Jatin Nagpal, Martin Schneider, Wagner Costa, Yanxun Yu, Joy Li, Raakhee Shankar, Benjamin Barsi-Rhyne, Alan Tran, Kristine Andersen, Aruna Varshney, Michelle Krzyzanowski, Denise Ferkey, Miri VanHoven, Piali Sengupta, Alexander Gottschalk, Noelle L'Etoile P216 Localization and Characterization of Odor Receptors in C. elegans Isabella DiBianca, Alyssa Quiogue, Carol Ghaffari, Opal Stayer-Wilburn, Vyoma Thakker, Mara Harwood, Shayda Maher, Lauren Resch, Sara Nathan, Cassidy Dalton, Alesha Cox-Harris, Rebecca Morton, Emily Jerome, Willa Mankins, Leesa Daffeh, Kumkum Tirumalasetty, Hannah Szentkuti, Jessica Sullivan, Genesis Hernandez, Kevin Fekrinia, Katie Gibbs, Nathan Hwang, Connor Lester, Berenice Mosqueda, Yen-Ping Hsueh, Bo Zhang, Noelle L'Etoile, Jared Young P217 Endocytic Machinery for Synaptic Vesicle Recycling Jihong Bai P218 Neuronal Output in C. elegans is Shaped by Glial Channels and Transporters via Regulation of Ionic Composition of Microenvironments Laura Bianchi, Christina K. Johnson, Ying Wang, Lu Han P219 Phosphorylation of MSI-1 Modulates its Function during Forgetting in C. elegans Csaba Boglari, Andreas Arnold, Fabian Peter, Pavlina Mastrandreas, Dominique J. - F. de Quervain, Andreas Papassotiropoulos, Attila Stetak P220 Identification of New Regulators of Acetylcholine Receptor Function in C. elegans Benjamin Bonneau, Luis Briseno-Roa, Viviane Lainé, Aurore-Cecile Valfort, Laure Granger, Maelle Jospin, Jean-Louis Bessereau P221 SAX-7/L1CAM and MPK-1/Erk Promote Coordinated Locomotion Melinda Moseley-Alldredge, Seema Sheoran, Hayoung Yoo, Calvin O'Keefe, Janet Richmond, Lihsia Chen P222 Roles of endophilins A, B and of clathrin at the Plasma Membrane and the Endosomal Membrane in Synaptic Vesicle Recycling Barbara Jánosi, Szi-chieh Yu, Jana F. Liewald, Sebastian Wabnig, Alexander Gottschalk P223 Synaptic Asymmetry in the ASE to AWC Connection Garrett Lee, Leo Tang, Steven Cook, Hannes Buelow P224 Genetic and Pharmacological Targeting of a BK Channel in Aging C. elegans Slows Motor Aging and Extends Lifespan Huahua Li, Guang Li, Jianke Gong, Jie Liu, Shawn XZ Xu P225 Investigating how the DAF-7/TGF-beta Signaling Pathway Regulates Abundance of the C. elegans glutamate receptor GLR-1 Annette McGehee, Ajia Zimmermann, Shannon McLaughlin, Lily Johnsky, Josette Nammour P226 Characterization of Dopamine-Gated Ion Channels Endogenous to C. elegans Neurons Joseph Pick, Niels Ringstad P227 Comparative Genomics of the Nematode cla-1 Locus Jim Rand, Jacob R. Manjarrez P228 Understanding DAF-19A Isoform as a Regulator of Isoform DAF-19C and a Repressor of gakh-1 Nabor Vazquez, Elizabeth De Stasio P229 Presynaptic Autophagy Christine Wnukowski, Nathan Okerlund, Eric Bend, Robert Hobson, Erik Jorgensen P230 Long-Term Hydrogel Immobilization for Light Sheet Imaging of Optogenetically-Stimulated Organisms Kyra Burnett, Ross Lagoy, Jeremy Florman, Mark Alkema, Dirk Albrecht

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior P231 Mapping Cell Position in the Developing Caenorhabditis elegans Embryo Ryan Christensen, Alexandra Bokinsky, Anthony Santella, Mark Moyle, Yicong Wu, Min Guo, Evan Ardiel, Brandon Harvey, William Duncan, Michael Levin, Nensi Karaj, Andrew Lauziere, Evan McCreedy, William Mohler, Daniel Colón-Ramos, Zhirong Bao, Hari Shroff P232 Machine Learning for Automatic Analysis of Animal Behavior John M. Day, Adam J. Iliff, Shawn Xu P233 Functional Proteomics Identified an Upstream Transcription Complex Promoting piRNA Biogenesis in C. elegans Shouhong Guang, Chenchun Weng, Asia Kosalka, Eric Miska P234 A Unified Method to Analyze the Behavioral States and Features during Animal’s Navigation by Machine Learning Kotaro Kimura, Shuhei Yamazaki, Ken Yoda, Takuya Maekawa P235 Automated Whole-Organism Functional Screening Technologies Identify Modulators of Optogenetically-Evoked Calcium Activity in C. elegans Ross Lagoy, Dirk Albrecht P236 FRET Imaging in Freely Moving Caenorhabditis elegans Reveals Conformational Changes in Twitchin Kinase Daniel Porto, Yohei Matsunaga, Barbara Franke, Rhys M. Williams, Hiroshi Qadota, Olga Mayans, Guy Benian, Hang Lu P237 MosTrap and the Standard Worm -- A New Platform for Forward Genetics Matthew S. Rich, M. Wayne Davis, Erik M. Jorgensen P238 Worm Analysis, Tracking and Annotation System (WATAS) Mingfei Shao, Jennifer Piane, Priya Deshpande, Yiyang Wang, Hongkyun Kim, Jacob Furst, Daniela S. Raicu P239 Progress Towards a Multi-Color Worm for Neuronal Identification Anuj Sharma, Jeffrey Nguyen, Francesco Randi, Andrew Leifer P240 The Great Worm Expansion: Collecting Connectivity Data with Expansion Microscopy Zainab Tanvir, Ivan Skvortsov, Jay Yu, Nicholas Barry, Elizabeth Cronin, Edward Boyden, Gal Haspel P241 A Flexible Pipeline for 3D Whole Brain Imaging with Deep Learning Chentao Wen, Takuya Miura, Yukako Fujie, Takayuki Teramoto, Takeshi Ishihara, Kotaro Kimura P242 Drug Synergy Slows Ageing and Improves Health Span through TGFβ and SREBP Lipid Signaling Tesfahun Dessale Admasu, Jan Gruber P243 plx-1/Plexin Specifies Spatial Synapse Distribution via rap-2/Rap2 and mig-15/TNIK Kota Mizumoto, Hideji Murakoshi, Mizuki Kurashina, Akihiro Shibata

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ORAL PRESENTATIONS Oral Talk #1

Nested Neuronal Oscillators Orchestrate Motor Actions across Timescales Manuel Zimmer1, Harris Kaplan1, Oriana Salazar Thula1 1 Research Institute of Molecular Pathology

Animal behavior is organized by assembling individual actions into action sequences and longer lasting motor programs that can span timescales from seconds to hours; the underlying mechanisms of this organization however remain elusive. Using whole-nervoussystem imaging, neuronal circuit manipulations and behavioral analysis, we addressed how the brain coordinates motor sequences across timescales in C. elegans. We identified three neuronal oscillators that act on different timescales to drive distinct behaviors: on the longest timescale, a brain wide oscillation commands the forward and reverse locomotion states, as described previously (Kato et al., 2015). Within the forward state, two distinct oscillations of the worm’s head and body serve different behavioral goals: traveling locomotion, as observed during roaming, is achieved through regular full-body undulations propagating from anterior to posterior along the entire body; in contrast, local exploration, as observed during dwelling, is achieved by head-casting behavior. Head casting is a specific postural syllable characteristic of additional head undulations that occur between full-body bends. Head-casting occurs at a higher frequency but strictly depends on the full-body bend oscillation phase. We identified two central pattern generator (CPG) candidates, one distributed across Bmotor neurons in the ventral cord and one comprising head and neck motor neurons. Both CPG candidates respectively promote full-body bends and head-casts within the forward motor state. Furthermore, head-cast-driving neurons show phase-nested activity relative to full-body bend-driving neurons, reflecting the behavioral organization. While these three neuronal oscillators hierarchically organize motor actions from long to shorter time scales via phase nesting, we also observe coupling in reverse, where the phase of the fast time-scale CPGs influences transitions between the long-time scale forwardbackward oscillations. Our findings reveal how phase nesting and coupling between neuronal oscillators organize behavior across time scales and in a hierarchical manner. Phase-nested neuronal oscillations and cross-frequency coupling are a recurring dynamical motif observed during orofacial and other cognitive behaviors in mammals. We hence propose an evolutionary origin of these motifs in the motor circuits of invertebrates and C. elegans as a tractable model organism to study their neuronal mechanisms.

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Oral Talk #2

Principles of Neural Coding for Efficient Navigation in Gradients Alon Zaslaver1, Eyal Itskovits1, Rotem Ruach1 1 Department of Genetics, The Silberman Institute of Life Science, Edmond J. Safra Campus, the Hebrew University of Jerusalem

Animal ability to effectively navigate towards food sources is central for survival. Here, using C. elegans nematodes, we revealed a previously unknown mechanism underlying efficient navigation in chemical gradients. This mechanism relies on the orchestrated dynamics of two types of chemosensory neurons: one coding gradients via stochastic pulsatile dynamics, and the second coding the gradients deterministically in a graded manner. The pulsatile dynamics obeys a novel principle where the activity adapts to the magnitude of the gradient derivative, allowing animals to take trajectories better oriented towards the target. The robust response of the second neuron to negative derivatives promotes immediate turns, thus alleviating costs of erroneous turns possibly incurred by the first neuron. This mechanism empowers an efficient navigation strategy which outperforms the classical biased-random walk strategy. Functional dynamics analyses of the entire chemosensory system revealed that various sensory neurons use this mechanism to code gradients of different stimuli. Thus, this newly discovered mechanism may be a common navigation strategy, and other sensory modalities may be using similar principles for efficient gradient-based navigation.

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Oral Talk #3

C. elegans Olfactory Neurons Fire Calcium-Mediated All-orNone Action Potentials Qiang Liu1, Philip Kidd1, May Dobosiewicz1, Cori Bargmann1,2 1 The Rockefeller University, 2Chan Zuckerberg Initiative

Unexpectedly, we find that C. elegans neurons can encode information through regenerative all-or-none action potentials, in addition to previously described graded potentials and plateau potentials. In a survey of current-voltage relationships in C. elegans neurons, we discovered that one of the olfactory neurons generate membrane potential spikes with defining characteristics of Hodgkin–Huxley action potentials. Pharmacology, ion substitution, and mutant analysis identified a voltage-gated CaV1 calcium channel and Shaker-type potassium channel that underlie the action potential dynamics. Additional potassium channels are predicted by simulation of action potentials with Hodgkin–Huxley and bifurcation models. Simultaneous patch-clamp recording and calcium imaging revealed spike-associated calcium signals that were also observed after odor stimulation of intact animals, suggesting that natural odor stimuli induce action potentials in this type of neurons. The stimulus regimes that elicited action potentials match its proposed specialized function in chemotaxis behaviors. Our results provide evidence that C. elegans neurons can use digital as well as analog coding schemes. The discovery of action potentials in C. elegans expands the computational repertoire of its nervous system and will likely shift future modeling of its neural coding and network dynamics.

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Oral Talk #4

A Tyraminergic Feedback-Loop Filters Reafferent Perception of Self-Movement in C. elegans Chemosensation Julia Riedl1, Manuel Zimmer1 1 Research Institute of Molecular Pathology IMP

To generate meaningful sensory representations of the environment nervous systems need to differentiate changes in the outside world from reafferent, i.e. self-produced, sensory signals. However, the mechanisms by which such motor related signals are relayed to and integrated by sensory circuits are incompletely understood. In this study we show that the activity of the BAG CO2 and O2 sensory neurons is directly modified by the motor state of the animal to suppress reafferent CO2 and O2 perception. Performing Ca2+-imaging of BAG activity in animals freely navigating various sensory environments, we found that during reversal states BAG is inhibited by an extrasynaptic tyramine signal, likely released from the reversal interneuron RIM. This neuromodulation required tyramine synthesis (tdc-1) and the tyramine-gated inhibitory chloride channel LGC-55, which we found to be expressed in BAG. Tyraminergic inhibition cancels out sensation of self-produced local fluctuations in CO2 and O2 encountered during reversals in diffusion limited environments, which we propose are ethologically relevant. Moreover, disrupting the feedback loop genetically (tdc-1, lgc-55), led to a mal-adaptive behavioral response to both reafferent and external CO2 stimuli: these animals showed strongly elevated reversal frequencies and dwell times. In conclusion, our work for the first time characterizes a corollary discharge signal in C. elegans that compensates for self-motionproduced reafferent sensory inputs, and which directly modulates a sensory neuron for this purpose. Our results show that appropriate sensorimotor integration in closed-loop sensory environments depends on motor feedback signals that can reach even the uppermost sensory layer of the nervous system.

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Oral Talk #5

The ASICs DEL-7 and DEL-3 Mediate Food Responses in an Enteric Serotonergic Neuron that Drives Persistent Behaviors Steven Flavell1, Jeffrey Rhoades1, Jessica Nelson2, Ijeoma Nwabudike1, Daniel Colon-Ramos2 1 Massachusetts Institute of Technology, 2Yale University School of Medicine

Neuromodulators like serotonin allow animals to generate sustained behavioral responses to environmental cues. Here, we identify conserved ion channels in an enteric serotonergic neuron that mediate its neural responses to food ingestion, and decipher how these responses drive sustained behaviors. We show that the C. elegans serotonergic neuron NSM acts as an enteric sensory neuron that acutely detects food ingestion. We identify the novel and conserved acid-sensing ion channels (ASICs) DEL-7 and DEL-3 as NSMenriched channels required for feeding-dependent NSM activity, which in turn drives persistent locomotor slowing. Point mutations that alter the DEL-7 channel change NSM dynamics and associated behavioral dynamics. Optogenetic studies reveal that distinct patterns of NSM activity drive different degrees of behavioral persistence. This study provides causal links between food ingestion, molecular and physiological properties of an enteric serotonergic neuron, and the persistence of feeding behaviors, yielding a new view of how enteric neurons control behavior.

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Oral Talk #6

How Does an Animal Move? An Integrative Model of C. elegans Forward Locomotion Tianqi Xu1, Jing Huo1, Shuai Shao1, Michelle Po2, Taizo Kawano2, Yangning Lu2, Min Wu2, Mei Zhen2, Quan Wen1 1 Hefei National laboratory for Physical Sciences at the Microscale, School of Life Science, University of Science and Technology of China, 2Dept. of Molecular Genetics, University of Toronto

A deep understanding of the neural basis of motor behaviors must integrate neuromuscular dynamics, mechanosensory feedback, as well as global command signals, to predict behavioral dynamics. By combining genetic analysis, optogenetic manipulation, calcium imaging, and computational modeling, we report on an integrative approach to define the circuit logic underlying locomotion in the roundworm C. elegans. The worm ventral nerve cord consists of a network of excitatory cholinergic motor neurons, including the A- and Btype that execute backward and forward movement, respectively, First, we found that some B-type motor neurons generated intrinsic rhythmic activity, constituting distributed oscillators. Second, AVB premotor interneurons used their electric inputs to drive bifurcation of B-type motor neuron dynamics, triggering their transition from stationary to oscillatory activity. Third, proprioceptive coupling between neighboring B-type motor neurons entrained the frequency of body oscillators, forcing coherent bending wave propagation. Despite substantial anatomical differences between the motor circuits of C. elegans and higher model organisms, converging principles govern coordinated locomotion.

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Oral Talk #7

Excitatory Motor Neurons are Local Oscillators for Reverse Locomotion Shangbang Gao1, Sihui Asuka Guan2, Anthony D. Fouad3, Jun Meng2, Taizo Kawano2, Yung-Chi Huang4, Yi Li1, Salvador Alcaire2, Wesley Hung2, Yangning Lu2, Yingchuan Billy Qi5, Yishi Jin5, Mark J. Alkema4, Christopher Fang-Yen3, Mei Zhen2 1 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, 2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 3Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, 4Department of Neurobiology, University of Massachusetts Medical School, 5Neurobiology Section, Division of Biological Sciences, University of California

Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: 1) forward and reverse movements are driven by different oscillators; 2) the cholinergic and excitatory class A motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive reverse movements without premotor interneurons; 3) the UNC-2 P/Q/N high voltage-activated calcium current underlies A motor neuron’s oscillation; 4) descending premotor interneurons AVA, via a conserved gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron’s intrinsic activity to regulate the propensity and maintenance of reverse movements. Thus, motor neurons themselves derive rhythms; descending interneurons regulate motor neuron activity to control the reversal motor state. These and previous findings exemplify compression - essential circuit property is conserved but executed by fewer number and layer of neurons in a small locomotor network.

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Oral Talk #8

Live Imaging of the C. elegans Connectome Oliver Hobert1, Hang Lu2 1 Columbia University, 2Georgia Tech

The National Science Foundation funds a program called Next Generation Networks for Neuroscience (NeuroNex) which aims to aid the research community to study the brain. In the context of this NeuroNex initiative, we plan develop and disseminate tools that will empower the C.elegans neuroscience community to study the connectome of C. elegans. In the first phase, our so-called technology hub will develop two sets of tools: The Hobert lab will use fluorescent-based reporter technology (GRASP with iBlinc serving as potential alternative) to generate a large number of transgenic C. elegans strains in which the main “edges” of the entire wiring diagram (i.e. pairwise combinations of neurons) are visualized. Such a resource would be unprecedented. This resource will be distributed throughout the C. elegans community to enable labs with long-standing interest in various aspects of neuronal development and function and with a focus on specific neuronal circuits and behaviors to use these synaptic labels to examine variability, development and plasticity of these connections. In parallel, the Lu lab will develop microfluidic-based and automated image analysis technologies to precisely quantify the structure of the connectome and to enable high-throughput screening of worm population for defects in synaptic wiring. Computer vision and machine learning will be used to automatically score disruptions of synaptic wiring to remove human bias and detect subtle and therefore potentially changes previously unseen.

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Oral Talk #9

The C. elegans Neuronal Gene Expression Map & Network (CeNGEN) Marc Hammarlund1, Oliver Hobert2, David Miller, Nenad Sestan 1 Yale University, 2Columbia University

Differential gene expression defines the form and function of individual neuron types in the brain, determines how individual neurons contribute to circuit physiology and behavior, and influences how individual neurons are affected by injury and disease. The C. elegans Neuronal Gene Expression Map & Network (CeNGEN) will establish a comprehensive molecular map of the entire C. elegans nervous system and will reveal regulatory networks and pathways that specify this map. CeNGEN provides a unique opportunity to elucidate the global control of neuron-specific gene expression and to relate gene expression to neuronal wiring and function. We outline here the goals and the design of CeNGEN.

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Oral Talk #10

Axonal Fusion: An Alternative Mechanism to Repair Injured Axons Massimo A Hilliard1 1 Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland

Understanding the molecular mechanisms that regulate axonal regeneration is essential for the development of effective therapies for nerve injuries. Despite substantial knowledge being gained into how axonal re-growth is initiated, our understanding of the mechanisms needed to achieve target reconnection remains very poor. In several species, reconnection of severed axons can occur through a process known as axonal fusion, whereby the proximal regrowing fragment recognizes and re-establishes both membrane and cytoplasmic continuity with its own separated distal fragment, preventing it from undergoing degeneration and restoring function. This represents a highly efficient way to re-establish the original connection between an injured neuron and its target tissue following injury. Using the nematode C. elegans as a model system, we have characterized this axonal fusion process at the molecular level. We discovered that the recognition of the separated axonal fragment by the regrowing axon uses the same conserved molecular elements previously shown to mediate the recognition of apoptotic cells by neighbouring phagocytes. Furthermore, we demonstrated that the reestablishment of membrane and cytoplasmic continuity between the two axonal fragments is achieved through the regulated expression and localization within the damaged neuron of fusogens, molecules known to mediate developmentally regulated cell-cell fusion in most eukaryotes. Finally, using a genetic approach, we have recently identified a new class of molecules that might function as regulators of the fusion machinery, facilitating axonal repair. These discoveries pave the way for the development of novel strategies for the treatment of nerve injury.

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior Oral Talk #11

An Autism-Causing Mutation Disrupts Axon Termination by Misregulating Lysosome Function Tyler M Buddell1, Christopher C Quinn1 1 University of Wisconsin-Milwaukee

The molecular mechanisms that underlie autism remain elusive, partly because of the large number of gene variants that contribute to the disorder. The Timothy syndrome mutation is a gain of function variant in a voltage gated calcium channel (VGCC) that can cause autism on its own, without contributions from other variants, providing a powerful avenue of investigation into the causes of autism. However, the Timothy syndrome mutation has not been linked to any specific defect in neurodevelopment and the mechanisms that underlie its role in autism are unknown. Here, we show that an egl-19(gof) mutation, which is equivalent to the Timothy syndrome mutation, causes defects in PLM axon termination in C. elegans. Our genetic analysis indicate that wildtype VGCCs negatively regulate PLM axon termination. Moreover, we find that VGCCs localize to a cellular compartment that is adjacent to lysosomes and that the axon termination defects caused by the egl-19(gof) Timothy syndrome mutation are suppressed by a mutation that disrupts lysosome function. Together, these results suggest that VGCCs can function with lysosomes to negatively regulate axon termination. Moreover, these results suggest that the Timothy syndrome mutation misregulates lysosomes to cause axon termination defects and reveal a potential role for lysosomes in autism.

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Oral Talk #12

Robo/SAX-3 Functions as a Wnt Co-Receptor during Directional Neurite Outgrowth in C. elegans Mei Ding1, Jiaming Wang1 1 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences

When axons navigate through a complex in vivo environment, at any given point they are probably confronted with several different guidance cues. Given the large number of different axon trajectories, it remains an enduring mystery how wiring specificity is achieved by a limited repertoire of secreted molecules. Both Slit-Robo and Wnt-Ror pathways are involved in neurite extension, but whether and how these two signaling pathways are interacted is largely unknown. Here, we found that instead of mediating Slit signaling, Robo could bind and respond to Wnt ligand. By forming a complex with the Ror receptor and Dsh effector, Robo receptor promotes signal transduction from Wnt to Dsh. Intriguingly, Dsh is asymmetrically distributed and the asymmetric distribution of Dsh is dependent on Robo, but not Ror receptor or Wnt ligand. Ror receptor was recently identified as a core component in PCP (planar cell polarity) pathway. The asymmetric subcellular localization of Dsh is therefore tightly linked to the directional neurite growth in vivo. Considering both Slit and Wnt signals are widely implicated in multiple cellular development processes and likely talk to each other at various places and times, this study will have profound influence on fundamental aspects of cellular and developmental biology in general.

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Oral Talk #13

A Transcription Factor Titration Mechanism for the Establishment and Maintenance of Neuron Identity Paschalis Kratsios1, Weidong Feng1, Pauline Dao1 1 Department of Neurobiology, University of Chicago

Neuron identity transformations have been widely described in nervous system development across species. Such transformations usually occur due to genetic removal of a specific regulatory factor with dual function. The regulatory factor can often activate genes that determine a specific neuronal identity and simultaneously repress genes that define an alternative identity. Here, we provide evidence for a novel, transcription factor (TF) titration mechanism of neuron identity transformation using the cholinergic motor neurons (MNs) of the Caenorhabditis elegans ventral nerve cord as a model. We find that removal of the conserved terminal selector-type transcription factor unc-3/Ebf results in partial neuron identity transformation characterized by loss of expression of cholinergic MN identity genes and concomitant gain of expression of GABAergic MN features. This dual UNC-3 function in cholinergic MNs is determined by the limited pool of available molecules of LIN-39 (Scr/Dfd/Hox4-Hox5), a mid-body Hox protein necessary for direct activation of both cholinergic and GABAergic MN identity genes. UNC-3 secures expression of cholinergic MN features through synergy with LIN-39 on the cis-regulatory region of cholinergic identity genes, thereby exhausting the pool of available LIN-39 molecules that could activate GABAergic MN features. Lowering UNC-3 or increasing LIN-39 protein levels in cholinergic MNs results in activation of GABAergic identity genes. This LIN-39mediated titration mechanism operates continuously, from development throughout adulthood, to ensure maintenance of cholinergic and exclusion of GABAergic MN features. The mechanism of TF titration represents a simple, yet economical strategy for neuron identity transformation with implications for the evolution of neuronal cell types.

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Oral Talk #14

WormGUIDES: Assembling and Accessing a Complete, Integrated Record of Neural Development Anthony Santella1, Mark Moyle2, Ryan Christensen3, Kris Barnes1, Gabriela Bosque2, Leighton Duncan2, William Duncan3, Li Fan1, Brandon Harvey3, Richard Ikegami2, Braden Katzman1, Abhishek Kumar3, Nhan Nguyen1, Titas Sengupta2, Pavak Shah1, Doris Tang1, Daniel ColónRamos2, Hari Shroff3, William A. Mohler4, Zhirong Bao1 1 Developmental Biology, Sloan Kettering Institute, 2Cell Biology and Neuroscience, Yale University School of Medicine, 3Section on High Resolution Optical Imaging, NIBIB NIH, 4Genetics & Developmental Biology & Center For Cell Analysis and Modeling, University of Connecticut Health Center

WormGUIDES is an interactive 4D atlas of C. elegans embryogenesis. Its goals are to (1) provide a reference atlas of neural development based on detailed time lapse measurements of individual neurite outgrowth; (2) cross reference worm community data with the 4D model and (3) provide an easy to use visualization platform for exploring and annotating the model as well as sharing insights. The major tracts of the nervous system are laid out early and added to over time. By the 1.5 fold stage most major structures are established. The early emergence of tracts motivates a hierarchal approach to modeling neural development. Our model contains three levels of neuronal structure: (1) Tracts; (2) Multi-cellular structures, small groups of co-labeled neurons; and (3) Individual cells. Neurites are threaded through the tracts based on measured tip. Approximately half of neurons in the embryo are currently represented in the atlas. In addition, the pharynx and hypoderm are modeled at the tissue level to provide a spatial context for neurons amid surrounding tissue. The set of approximately 182 markers slated for analysis cover almost all neurons. Additional imaging and analysis tools are being developed to capture all neurons and push our model to hatching. The nervous system emerges through a hierarchically organized process that is inherently dependent on spatial context. By providing a complete spatial-temporal atlas, WormGUIDES seeks to be a comprehensive tool for observing correlations between cells, forming testable hypothesis about their coordination and assembling and interpreting detailed records of observed collective behaviors.

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Oral Talk #15

Connecting Genes with Phenotypes for Epilepsy and Neurodegenerative Disease Kat McCormick1 1 NemaMetrix Product Talk

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Oral Talk #16

A Different Kind of Dendrite-Glia Interaction in C. elegans Maxwell G. Heiman1, Elizabeth R. Lamkin1, Ian G. McLachlan1 1 Harvard Medical School and Boston Children's Hospital

Glia and neurons interact through elaborate contacts that can modulate neuronal function. In C. elegans, dendrite-glia interactions have almost exclusively been studied in the context of sense organs like the amphid, in which sensory neurons form epithelial junctions with glia. This arrangement is reminiscent of vertebrate sense organs like the inner ear. In contrast, dendrite-glia contacts in the vertebrate brain are usually not epithelial. Thus, as an alternative model for dendrite-glia interaction, we turned to the non-epithelial gassensing neurons BAG and URX. Using super-resolution imaging, we found that these dendrites terminate in membranous elaborations that wrap around thumb-like protrusions of a single glial cell (the lateral ILso). Time-lapse imaging of embryonic BAG and URX suggests that dendrites attach early and are then stretched out during embryo elongation. This "retrograde extension" resembles what we observed previously in the amphid. However, while the amphid requires the apical ECM protein DYF-7 to prevent rupture of the developing neuroepithelium during this process, BAG and URX dendrites do not require DYF-7. We therefore used forward and candidate screens to identify molecules required for BAG/URX dendrite extension. We identified the cytoskeletal adaptor GRDN-1, the cell adhesion molecule SAX-7, and the scaffolding protein MAGI-1. These factors act in the glial cell and localize near the dendrite contact, suggesting they might promote BAG/URX dendrite extension by ensuring attachment to the glial partner. Homologs of these proteins are expressed in mammalian brain, suggesting that this dendrite-glia interaction may indeed more closely resemble the arrangement found in mammalian CNS.

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Oral Talk #17

“The Creation of Dendrites”: Axon-Dependent Dendritic Development and Maintenance in Somatosensory Neurons Nelson Ramirez1, Burcu Beyaz2, Benjamin Raja2, Julius Fredens3, Ken Nguyen2, Nils J. Færgeman3, David H. Hall2, Hannes E. Buelow1 1 Department of Genetics. Albert Einstein College of Medicine, 2Dominick P. Purpura Department of Neuroscience. Bronx, 3Department of Biochemistry and Molecular Biology. University of Southern Denmark.

Dendrite formation is a key step for the correct function and assembly of the nervous system. Development and maintenance of dendrites can be shaped by the activity of presynaptic axons, but little is known about activity-independent functions of axons during the formation of dendrites. Here, we provide evidence that the axonal processes of ALA neuron shape the primary dendrites of the PVD somatosensory neurons. Through a combination of laser-ablation microsurgery, electron microscopy observations and molecular genetic experiments, we demonstrate that PVD 1° dendritic branches require the physical presence of the ALA axons but do not depend on ALA synaptic activity. Disruptions in ALA axon position by loss of the conserved extracellular matrix protein MIG6/Papilin or the UNC-6/Netrin pathway produce primary dendrite guidance defects, supporting the idea that axon-dendrite adhesion is another source of guidance for dendrite formation. We have found that ALA-PVD interactions require two distinct functions of the cell adhesion molecule SAX-7/L1CAM: First, SAX-7/L1CAM functions in ALA to facilitate outgrowth of the PVD 1º branch, likely in a manner dependent on the Menorin pathway. Second, SAX-7/L1CAM serves a post-developmental role to maintain fasciculation between the ALA axons and PVD 1° dendrites. The maintenance function of SAX7/L1CAM is dependent on expression in both ALA and PVD neurons and may involve homophilic interactions. Taken together, we demonstrate that axons can serve as scaffolds through contact-dependent but activity-independent interactions during development and maintenance of somatosensory dendrites.

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Oral Talk #18

Axonal Tiling in D-Type Motor Neurons Ardalan Hendi1, Kota Mizumoto1 1 Department of Zoology, University of British Columbia

Precise innervation patterning of neurons is essential for the proper functioning of the nervous system. Neuronal tiling is one such mechanism where axons and dendrites of neighboring neurons of the same class form complete but non-overlapping receptive fields. Here, to reveal the novel mechanisms of tiling, we focus on the axonal tiling of the DDclass of GABAergic motor neurons. Previous electron microscopy has revealed that the axon and dendrite of a DD neuron does not overlap with those of neighboring DD neurons (DD1-DD6) (White et al., 1976). By using cell specific promoters and fluorescent proteins, we established markers to visualize axons or synapses of DD5 and DD6. Using these markers, we found that axonal tiling between DD5 and DD6 depends on EGL-20/Wnt. In egl-20/wnt mutants, DD5 axon extends posteriorly, resulting in significant overlap between DD5 and DD6 axons, suggesting that Wnts have a repulsive role in mediating axonal tiling. Interestingly, we found that despite the axonal overlap, in egl-20/wnt mutants, DD5 did not form synapses in the region of overlap, suggesting the existence of another mechanism that restrict synapse formation in DD neurons. We found two innexins, unc-9 and unc-7, which form gap junctions between DD neurons are responsible for restricting DD synapses. In egl-20; unc-9 unc-7 triple mutants, DD5 formed synapses in the axonal region that overlaps with DD6 axon, resulting in significant overlap between DD5 and DD6 synaptic regions. Taken together, we propose that Wnts and innexins act in concert to establish axonal tiling and restrict synapse formation.

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Oral Talk #19

An Update about WormBase Tools Wen Chen1, Todd Harris1 1 Caltech, WormBase

WormBase, now part of the Alliance of Genome Resources, has been serving the community since 2000 by providing up-to-date biological data about nematode genomes and research from literature. WormBase continues to expand as it seeks to cover all data from the growing community, which includes those from new technologies and more species. WormBase has been striving to provide users with tools to navigate through the vast amount of data in our database to find what they need. Over the years, these search tools include Textpresso, Ontology Browser, WormMine, SimpleMine, WormBase SPELL, Parasite WormMart, and JBrowse. We will discuss new features for some of these tools and hope to hear your feedback At the same time, the annual rate of publication by the worm community has tripled since 2000, A top priority for WormBase is figuring out how to keep up with this increased rate of data generation by our communities. In addition, we have a mission to collect valuable data that will not make it into a publication. We encourage community members to use our online forms to submit published data missing from our database, especially for genetic or protein interactions, phenotypes, and allele characterizations. To collect those data that have been lost from publication, we created Micropublication: biology, a peer-reviewed journal where single experiments are the article. When accepted, these articles are published online, their data are curated in WormBase, and the author receives a DOI that can be used as with any other article citation.

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Multiple Roles of apl-1, the C. elegans Human APP Orthologue Chris Li1, Mark Palmer1, Vanessa Marfil1, Ji-Sup Yang1, Valerie Moscoso1, Phachara Stancu1, Swera Cheema1, Raymund Zou1, Anan Kazi1 1 City College of New York

Deposition of dense plaques in the brain is one of the postmortem criteria of Alzheimer’s disease. The major component of these plaques is the beta-amyloid peptide, which is derived from the amyloid precursor protein (APP). Knockout of the mammalian APP family results in postnatal lethality and type II lissencephaly, suggesting that the APP family has an essential role in viability and neurodevelopment. apl-1 is the only APP orthologue in C. elegans; knockout or overexpression of apl-1 results in larval lethality, suggesting that apl1, like APP, has an essential role. The apl-1 lethality can be rescued by expression of apl1 only in neurons, indicating that neuronally-expressed apl-1 is essential for viability.

apl-1(yn5) is a temperature-sensitive (ts) allele; mutants have several phenotypes at the permissive temperature and show lethality at the restrictive temperature. moa-1, which encodes a receptor protein tyrosine pseudo-phosphatase (RPTPP), is a suppressor of the ts apl-1(yn5) lethality. Interestingly, overexpression of moa-1 leads to defects in male tail morphogenesis and mating, which can be suppressed by apl-1(yn5). Hence, moa-1 and apl-1 appear to have context-dependent genetic relationships. Male tail morphology is controlled by the heterochronic, sex differentiation, and Wnt pathways, whose genes are used in multiple contexts. We are exploring the genetic interactions of apl-1 and moa-1 with many of the genes in male tail morphogenesis. We envision that using male tail development to examine apl-1 function will highlight genes involved in nervous system function and lead to understanding the normal physiological function of the APP family of genes.

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Identification of New Ionotropic Receptors for Monoamines And Other Neurotransmitters Iris Hardege1, Julia Morud1, William R Schafer1 1 MRC Laboratory of Molecular Biology

In C. elegans, extrasynaptic neuromodulation is extensive; most neurons expressing monoamine-activated GPCRs receive no synapses from monoamine-releasing neurons. Conversely, C. elegans possess neurons that do not produce classical neurotransmitters, instead solely produce monoamines, the majority of neurons postsynaptic to these do not express known aminergic receptors, neither GPCRs nor ion channels. We therefore investigated whether ligand-gated ion channels (LGICs) may mediate transmission between aminergic neurons and their postsynaptic partners. The Cys-loop family of LGICs is vastly expanded in C. elegans, and several family members are monoamine-gated. Most of these channels remain poorly characterised, lacking known agonists, expression pattern or biological function. Using heterologous expression in Xenopus oocytes we characterised agonist sensitivity and ion selectivity of several novel C. elegans LGICs. We identified GGR-3 and LGC-54 as dopamine and tyramine-gated anion channels, members of the subfamily containing MOD1 and LGC-55. Fluorescent reporters identified expression of ggr-3 and lgc-54 in some of the major postsynaptic targets of dopaminergic neurons. Thus, we hypothesise that channels of this subfamily, may mediate most synaptic transmission from dopaminergic neurons in C. elegans. With the intent to understand the relationship between synaptic and extrasynaptic neurotransmission in C. elegans we aim to elucidate the expression and electrophysiology of other uncharacterised LGIC subfamilies. For example, we identified acetylcholine and choline as agonists for GGR-1 and GGR-2. Using this approach, we expect to deorphanise many of these channels; which if they are expressed in essential tissues, may provide a powerful approach for identifying potential new drug targets for antihelminthics.

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Oral Talk #22

Bacterial Diet Modulates Cholinergic Signaling through Vitamin B12-Dependent Metabolic Changes in the Intestine Wookyu Kang1, Mark J Alkema1 1 Department of Neurobiology, University of Massachusetts Medical School

A growing body of evidence shows that diet and gut microbiota influence brain function and mental health. However, the molecular basis of the complex interactions between diet, metabolism, and the brain function remain largely unknown. Here, we examined the effect of various species of bacterial diets on a C. elegans model for a channelopathy, a novel gain-of-function (gf) mutant for the presynaptic voltage-gated calcium channel UNC2/CaV2α, to identify bacterial metabolites that affect neural function. We identify vitamin B12, produced by Comamonas, as the key metabolite that suppresses excitatory synaptic transmission and hyperactive behavioral phenotype of unc-2/CaV2α(gf) mutants. We find that vitamin B12-dependent methionine/SAM cycle reduces cholinergic transmission. Choline metabolism is closely linked methionine/SAM cycle. We provide evidence that vitamin B12 suppresses cholinergic transmission by decreasing the supply of the free choline, a precursor for the neuronal synthesis of acetylcholine. Our findings demonstrate a mechanistic link between diet, vitamin B12, gut metabolism, and nervous system function, and provide molecular insight between the interaction of the microbiome and behavior.

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Regulation of the C. elegans Nicotinic Acetylcholine Receptor ACR-16 is Calcium-Dependent Ashley A. Martin1, Janet Richmond1 1 University of Illinois at Chicago

Nicotinic acetylcholine receptors (NAChR) are present in many excitable tissues. These receptors have roles in neuromodulation, synaptic plasticity, and neuroprotection and NAChR mislocalization or functional deficits are associated with many neurological disease states. Identifying mechanisms that regulate nAChR expression and function will play a critical role in informing our understanding of normal and pathological conditions and possibly offer potential therapeutic advances. Using Caenorhabditis elegans, a forward genetic screen was done to isolate regulators of the vertebrate α7 nAChR homologue ACR-16. From this screen a novel regulator of the ACR-16 receptor was identified, the sarco(endo)plasmic reticulum calcium ATPase sca-1. The sca-1 mutant specifically affects ACR-16 receptor levels at the NMJ as well as receptor functionality. In the sca-1 mutants synaptic transmission was reduced, however responses to pressure-ejected nicotine were wild type, implying ACR-16 receptors are functional but mislocalized. Based SCA-1’s role as a calcium pump, changes in calcium homeostasis and regulation were examined in the mutant background. sca-1 mutants had increased baseline cytosolic calcium levels, whereas calcium transients were unaffected. When the calcium activated potassium channel mutant, slo-1, was used to increase baseline calcium levels, a similar reduction in ACR-16 receptors was observed. Together these data suggest that the α7-like NAChR ACR-16 is regulated in a calcium-dependent manner. To identify possible calcium-mediated mechanisms, we examined the protein kinase CAMKII. In the sca-1 mutant, the loss of function CAMKII mutant unc-43 rescued the significant reduction of ACR-16 receptors. Current studies are testing if CAMKII’s act directly or indirectly to phosphorylate ACR-16 receptors.

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Metabotropic and Ionotropic Glutamate Receptors Coordinately Regulate Olfactory Learning in AIB Interneurons Kotaro Kimura1,3, Shuhei Yamazaki1, Takeshi Ishihara2 1 Osaka University, 2Kyushu University, 3Nagoya City University

Metabotropic glutamate receptors (mGluRs) are known to play critical roles in multiple types of learning, such as motor learning, spatial learning, and fear conditioning, although the precise in vivo mechanism has been unclear. We report here a novel mechanism of learning involving mGluRs in worms. We have previously demonstrated that worm's avoidance behavior to the repulsive odor 2-nonanone is enhanced by odor pre-exposure for 1 h, and that this non-associative learning is regulated by dopamine and neuropeptide signalings (Kimura et al., 2010). Recently, we found that MGL-2, a homolog of group I mGluRs, is also required for this repulsive odor learning in a pair of AIB neurons, which is responsible for backward movement. Calcium imaging under quantitative odor stimulus (Tanimoto et al., 2017) revealed that, although ASH neurons in wild-type worms without learning responded to increases in 2-nonanone concentration, AIB neurons did not, despite their substantial synaptic connections from the ASH neurons. Interestingly, the AIB neurons did respond to the odor increase after learning, which required MGL-2 activity in the AIB neurons. We also found that GLR-5, an AMPA/kainite-type glutamate receptor (iGluR), also contributes to repulsive odor learning in AIB neurons. This is markedly different from the other well-known examples, such as NMDAR-dependent activation of “silent synapses” or mGluR-dependent endocytosis of iGluR during long-term depression (LTD). Thus, metabotropic and ionotropic glutamate receptors likely coordinate to modulate neural activity for learning by a novel mechanism.

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Oral Talk #25

Enhanced High-Throughput Phenotyping of C. elegans Using the COPAS Vision Flow Cytometer with Imaging Capabilities Mikalai Malinouski1 1 UnionBioMetrica

Union Biometrica is designing and building tools for high-throughput analysis and handling of C.elegans. Over 100 papers are published in peer-reviewed journals using “worm sorters” for high-throughput phenotypical characterization and dispensing of C. elegans. This year we have developed the next generation flow cytometer capable of imaging and dispensing different stages and populations of C. elegans. Adding imaging capability to COPAS platform greatly enhances the phenotyping of samples by providing morphological and spatial information of worms while maintaining speed (~20 worms/sec). The collected images and flow cytometry measurements (size, optical density, fluorescence intensity and localization) are synchronized so that objects dispensed to Petri dishes, tubes or wells of multiwell plates can be traced back to their corresponding image. We will show examples of using COPAS Vision for phenotyping populations of C.elegans strains and a typical workflow for highthroughput analysis.

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Vascular Endothelial Growth Factor (VEGF) Receptor-related VER-1 and VER-4 Regulate Glutamatergic Behavior by Promoting Cell Surface Levels of GLR-1 Glutamate Receptors Peter Juo1, Eric Luth1, Carmino Riccio1, Julia Hofer1, Kaitlin Markoja1 1 Tufts University School of Medicine

Regulation of glutamate receptor trafficking is important for controlling synaptic strength, learning and memory. We identified the Vascular Endothelial Growth Factor (VEGF) Receptor-related genes ver-1 and ver-4, in an RNAi screen for novel genes involved in a glutamatergic, mechanosensory reflex known as the nose-touch (NOT) response. Mammalian VEGF signaling plays important roles in vascular development, however emerging evidence indicates key roles for VEGF in the nervous system. We found that ver1 and ver-4 loss-of-function mutants have strong defects in the NOT response with no alterations in neuromuscular junction function. The NOT defects can be rescued by expression of wild type ver-1 or ver-4 cDNA in GLR-1-expressing interneurons, but not in upstream ASH sensory neurons of the NOT circuit. Consistent with these results, ASH process morphology and the axonal distribution of presynaptic RAB-3 appear normal in the ver mutants. Analysis of GLR-1 tagged with pH-sensitive-Superecliptic phluorin revealed that ver-1 and ver-4 mutants have reduced surface levels of GLR-1. Furthermore, blocking GLR-1 endocytosis with unc-11/AP180 clathrin adaptin mutants abrogates the effects of the ver mutants on surface GLR-1, suggesting that the VERs likely act on a postendocytic pool of receptors. Finally, loss-of-function mutations in pvf-1, the only known VEGF homolog, also results in defects in the NOT response and GLR-1 surface levels. Together, these data suggest a model where the ligand PVF-1 and the VEGFRs VER-1 and VER-4 regulate glutamatergic behavior by promoting recycling of GLR-1 to the neuronal cell surface.

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Oral Talk #27

Neuromedin U Signaling in Experience-Dependent Salt Chemotaxis Jan Watteyne1, Petrus Van der Auwera1, Clare Foley1, Katleen Peymen1, Liliane Schoofs1, Isabel Beets2 1 Department of Biology, Functional Genomics and Proteomics Group, KU Leuven, 2Cell Biology Division, Medical Research Council Laboratory of Molecular Biology

Behavior is highly flexible and adaptive, and the brain’s ability to learn and remember from experience allows making predictions on future events and adjusting choices appropriately. Neuropeptides are important behavioral neuromodulators that are mainly thought to exert their function through G protein-coupled receptors (GPCRs). Caenorhabditis elegans displays various adaptive behaviors, including experience-driven modulation of salt chemotaxis, a type of associative learning in which normal chemotaxis towards salt is modulated by pre-exposure to this substance in the absence of food. The evolutionarily conserved NMUR-1 receptor was found to potentiate this plastic behavior when assaying various GPCR mutant worms in a candidate gene approach. Next, our reverse pharmacology pipeline identified Neuromedin U like peptides to activate the receptor in vitro. The behavior of worms defective in nmur-1 was quantified by video-tracking. Localization and rescue experiments showed the receptor to be present in various interneurons and sensory neurons, while neuropeptide expression is restricted to one sensory neuron, ASG. Neuronal silencing and imaging techniques are currently being utilized on this neuropeptide-releasing neuron to uncover the timing and cues leading to peptide release. Our findings demonstrate how neuropeptidergic input can be recruited to alter sensory processing and eventually tune the appropriate locomotor program in response to a detrimental sensory context. Furthermore, our data may also help assigning a potentially novel role for Neuromedin U signaling in the regulation of learning and memory throughout animal evolution, besides its well-characterized conserved role in feeding and energy homeostasis.

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Slowpoke, Where'd You Go? Timothy Cheung1,2,3, Kelly Oh1, Hongkyun Kim1 1 Department of Cell Biology & Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine & Science, 2Dr. William M. Scholl College of Podiatric Medicine, Rosalind Franklin University of Medicine & Science, 3School of Gradudate and Postdoctoral Studies, Rosalind Franklin University of Medicine & Science

The SLO-1 BK channel is a large conductance, voltage- and calcium-dependent potassium channel that controls synaptic transmission and muscle excitation. However, the mechanism underlying BK channel trafficking, thus controlling channel level, has yet to be clearly defined. In a previous C. elegans genetic study, the ER membrane protein ERG-28 was identified as a regulator of SLO-1 trafficking from the ER to the Golgi complex; SLO-1 level is drastically reduced in the absence of ERG-28. We hypothesize that without ERG28, SLO-1 is recognized by the ERAD (ER associated degradation) system and inactivation of ERAD increases SLO-1 channel level. Using a candidate gene approach, we identified sel-11, an ER-resident E3 ubiquitin ligase, as an important regulator of SLO-1 degradation in erg-28 mutants. Introduction of sel-11 mutation to erg-28 mutant resulted in significant recovery of SLO-1 levels at the plasma membrane. Moreover, the recovered SLO-1 at the plasma membrane is functional as sel-11 mutation suppressed erg-28 mutant phenotype. We also examined the relationship between sel-11 and ddi-1, a gene encoding an aspartic protease that participates in the degradation of SLO-1 in erg-28 mutant. The SLO-1 channel levels of ddi-1;sel-11 erg-28 triple mutant and sel-11 erg-28 or ddi-1;erg-28 double mutants were not significantly different, suggesting a shared pathway of SLO-1 degradation between SEL-11 and DDI-1. Together, our data show that the overall level of SLO-1 channel is regulated in the ER by the concerted action between ERG-28 and the ERAD machinery, in which SEL-11 and DDI-1 are main components.

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Modulation of the NCA Ion Channels by Dopamine, GRK-2, and ERK Signaling Irini Topalidou1, Brantley Coleman1, Michael Ailion1 1 Department of Biochemistry, University of Washington

Gq is a heterotrimeric G protein that regulates neuronal activity through distinct effectors, such as the Gq effector phospholipase Cβ and the small GTPase Rho. Recently we found that the C. elegans orthologs of the NALCN ion channel, NCA-1 and NCA-2, are activated by a signaling pathway acting downstream of Gq and Rho. NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. To identify additional molecules important for Gq-Rho-Nca signaling in neurons, we performed a forward genetic screen for suppressors of activated Gq and isolated mutations in genes encoding the GPCR kinase GRK-2 and the MAP kinase scaffold protein KSR-1. Using structure-function analysis and genetic epistasis experiments we found that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA1 and NCA-2 activity. We also found that KSR-1 modulates NCA-1 and NCA-2 activity in a dopamine-dependent manner, downstream of or in parallel to the Gq-Rho pathway. Interestingly, the core ERK pathway, but not LET-60/Ras, participates in this Gq-Rho pathway. Through cell-specific rescuing experiments, we found that GRK-2, DOP-3, and KSR-1 act in premotor interneurons to modulate NCA channel function. Finally, we found that NCA activity is negatively regulated by exogenous dopamine or by optogenetic activation of the dopaminergic neurons. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels through GRK-2 and the ERK pathway.

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Chemical and Electrical Synapses Cooperate in a Circuit Motif for Sensory Integration May Dobosiewicz1, Cori Bargmann1 1 The Rockefeller University

Neurons communicate through both electrical and chemical synapses to guide behavior. ~10% of the synapses predicted in the C. elegans wiring diagram are electrical, with most neurons having both electrical and chemical synapses. Here, we ask how neuronal circuits use these different modes of communication to integrate sensory information. C. elegans senses certain attractive odors with the sensory neuron AWA, which forms chemical and electrical synapses onto several interconnected sensory neurons and interneurons. One AWA target is the interneuron AIA, which AWA connects to through a predicted electrical synapse. In calcium imaging experiments, AIA responds reliably to pulses of the AWA-sensed odor diacetyl, a byproduct of bacterial fermentation. These AIA responses are preserved in animals lacking intact AWA chemical synapses, consistent with a functional AWA-AIA electrical synapse. Using optogenetics to probe the AWA-AIA connection, we found that AWA stimulation, unlike odor, does not reliably produce downstream AIA responses. Chemical synapses from elsewhere in the circuit affect both the reliability and timing of these AIA responses. Robust AIA responses appear to require both electrical synaptic signaling from AWA and release of inhibition from two distinct sensory neurons. Our results suggest that ecologically relevant odors like diacetyl have complex sensory representations that cannot be mimicked by direct stimulation of a single sensory neuron. We believe that AIA activity preferentially encodes “food” signals that activate multiple sensory neurons.

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Serotonin Disinhibits the ASH Nociceptive Neurons by Suppressing Ca2+-Dependent Negative Feedback Bruce Bamber1, Paul David Edward Williams2 1 Department of Biological Sciences, University of Toledo, 2Department of Biomedical Sciences, Iowa State University

Neuromodulators such as serotonin (5-HT) alter neuronal excitability and synaptic strengths, and define different behavioral states. Neuromodulator-dependent changes in neuronal activity patterns are frequently measured using calcium reporters, since calcium imaging can easily be performed on intact functioning nervous systems. With only 302 neurons, the nematode Caenorhabditis elegans provides a relatively simple, yet powerful, system to understand neuromodulation at the level of individual neurons. C. elegans hermaphrodites are repelled by 1-octanol, and the initiation of these aversive responses is potentiated by 5-HT. 5-HT acts on the ASH polymodal nociceptors that sense the 1-octanol stimulus. Surprisingly, 5-HT suppresses ASH Ca2+ transients while simultaneously potentiating 1-octanol-dependent ASH depolarization. Three observations explain this seemingly inverse relationship: First, 5-HT acts downstream of depolarization, through Gαq-mediated signaling and calcineurin, to inhibit the EGL-19 voltage-gated Ca2+ channels, which normally gate Ca2+ entry into the ASH cytoplasm. Second, Ca2+ acts a second messenger in this system to inhibit ASH depolarization. Third, the Ca2+-activated K+ channel, SLO-1, acts downstream of 5-HT, and is a critical regulator of ASH response dynamics. These findings define a Ca2+-dependent inhibitory feedback loop, and demonstrate that 5-HT disinhibits the ASHs by attenuating the strength of the negative feedback. These results establish a novel 5-HT signal transduction pathway, and demonstrate that neuromodulators can change Ca2+ signals and depolarization amplitudes in opposite directions, simultaneously, within a single neuron.

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Nematode Research Technology: The Future is Simple Shawn Lockery1 1 University of Oregon

Rapid growth in fast, inexpensive technologies for fabrication at the micro and meso scales has the potential to fundamentally transform basic and translational research in C. elegans and other nematodes. However, transferring new devices from the prototype stage in academic engineering labs to the bench top in front-line biology labs remains a critical bottle neck. One commonly recognized problem – that biology labs lack the equipment and expertise to replicate engineering prototypes – can in some cased be overcome through commercial production of devices. However, another problem is that many devices, particularly those with active components such as valves or read-outs such as image processing or electrophysiology, require peripheral systems that demand yet another layer of expertise. At NemaMetrix and the Lockery lab, we are seeking to open holes in the technology transfer barrier by developing simple devices that have few, if any, peripheral requirements, without sacrificing broad application in key areas such of interest to C. elegans researchers. This presentation will discuss specific examples of this design philosophy in the context of the biological problems that motivated them and the new types of findings they generate.

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The Development of a Synthetic Neurotransmission System Navin Pokala1 1 New York Institute of Technology (NYIT)

A synthetic and orthogonal neurotransmission system may be useful for testing models of neural circuit function. Nematodes do not appear to synthesize or use histamine, making it a potential platform for building such a system. We have expressed histamine synthesis and synaptic vesicle packaging machinery in specific C elegans neurons (ASH, pdf-1+ cells), transforming them into synthetically histaminergic cells that signal to cells expressing transgenic histamine-activated receptors (AVA, pdfr-1+ cells respectively). This orthogonal synthetic neurotransmission system functions with both ionotropic and metabotropic receptors. Since worms do not have histamine degradation or re-uptake systems, synthetic histaminergic signaling is sustained over longer timescales than endogenous transmitters. Incorporating histamine degradation systems may reduce signaling durations to more biologically relevant timescales.

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Fast, Versatile, and Quantitative Annotation of Complex Phenotypes Kathleen E Bates1, Shen Jiang3, Hang Lu2 1 Interdisciplinary Program in Bioengineering, Institute of Biosciences and Bioegineering, Georgia Institute of Technology, 2School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 3School of Computer Science, Georgia Institute of Technology

The ease of collecting large image datasets has led to a shift in bottleneck from image collection to image analysis across many disciplines, including connectomics and analysis of complex behaviors. Although specialized computational pipelines are emerging, they require significant effort to construct, are error-prone, and may rely on human annotation of many images. Moreover, tools for quantitative annotation are problem-specific, complex to operate, and difficult to parallelize. We report a versatile, fast and quantitative method for image annotation using a smartphone app and demonstrate its use by annotating complex postures in C. elegans that otherwise require >20 minutes/frame to solve computationally. To significantly increase annotation speed, we took advantage of the relative ease of drawing with a finger, as well the ease of distributing data through an app. This enabled us to quickly collect >30,000 annotations of self-occluding worm postures, which we used to reconstruct behavior of individuals. Compared to the state-of-the-art computational method, our methodology provides equivalent results >100-fold faster. We then used annotations to reexamine the worm’s posture space, revealing a significant change suggestive of an important role of large-angle turning behavior. The app is open-source, and available at https://sites.google.com/view/wurm/home. The app is indiscriminant to the nature of images; we have annotated plant roots and stem cells using the same system. We expect that our app will be useful both as an alternative to creating complex image processing pipelines and as a simple way to generate consensus ground truths towards improving machine learning algorithms for image processing.

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Actuation and Imaging of Excitable Cell Activity using Microbial Rhodopsins as Genetically Encoded Voltage Sensors Amelie Bergs1, Negin AzimiHashemi1, Rebecca Scheiwe1, Wagner Steuer Costa1, Jana F. Liewald1, Alexander Gottschalk1 1 Goethe University, Buchmann Institute

To identify functional connections and to control neural circuits and the behaviors they drive, optogenetic methods to actuate neural activity were established in recent years. However, methods to simultaneously image activity based on membrane voltage are lagging behind. We probed the utility of voltage-sensing bacteriorhodopsin (Arch- or Mac)-based optogenetic tools in excitable cells, to visualize changes in membrane potential based on spontaneous activity or triggered by ChR2 or anion channelrhodopsin (ACR). Pump-dead Arch mutants (D95N, QuasAr) and electrochromic (eFRET-)based sensors (QuasArmOrange, MacQ-mCitrine) reliably monitored voltage dynamics in the pharynx, exhibiting up to 25% change in fluorescence intensity (ΔF/F) during an action potential (AP). Employing synthetic retinal analogs, we could even double the signal and its voltagedependent changes, enabling imaging at low excitation light intensity. Furthermore, these recordings could reliably detect changes in the pharynx AP size and duration based on mutations in the EGL-19 VGCC, or on nemadipine, a reported VGCC blocker. By appropriate imaging conditions, we could simultaneously record pharynx muscle contractions and correlate them with with voltage dynamics (muscle contractions lagged behind voltage changes by 50-80 ms). In body-wall muscles, strong fluorescence increases (>30%) could be evoked by photostimulation of cholinergic neurons using ChR2. The membrane potential could be gradually tuned along the ChR2 action spectrum by adjusting the excitation wavelength. Currently we test the utility of these tools in neurons, and results will be reported at the meeting. In the future, we aim at achieving all-optical electrophysiology (‘optogenetic voltage clamp’) in live and behaving animals.

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ADARs and A-to-I RNA Editing Regulate Gene Expression in the Nervous System Heather Hundley1, Sarah Deffit1, Brian Yee3, Aidan Manning1, Suba Rajendren2, Pranathi Vadlamani1, Emily Wheeler3, Alan Domissy3, Michael Washburn2, Gene Yeo3 1 Medical Sciences Program, Indiana University, 2Department of Biology, Indiana University, 3 Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego

Adenosine deaminases that act on RNA (ADARs) are proteins that alter gene expression both by catalyzing adenosine(A- to-inosine(I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome. High-throughput sequencing revealed over 7,300 editing sites in the neural editome. Additionally, differential expression analysis identified 169 genes with altered expression in neural cells lacking adr-2. To identify potential ADR-2 targets responsible for defects in chemotaxis, our study further focused on genes known to regulate this biological process. Here, clec-41, a gene previously found to be important for proper worm locomotion was found to be expressed and edited within the 3’ UTR in neural cells. In addition, clec-41 transcripts were differentially expressed in adr-2(-) neural cells. Strikingly, transgenic expression of clec-41 in neural cells of adr-2 deficient worms was sufficient to rescue the aberrant chemotaxis of these animals. Furthermore, expression of a mutant ADR-2 protein capable of binding clec-41, but not editing, was not sufficient for proper clec-41 expression or chemotaxis, indicating deamination is required for both gene regulation and chemotaxis. This is the first study to link noncoding A-to-I editing and altered expression of a specific transcript with a neurological consequence resulting from loss of ADARs.

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The Importance of Rest during the Post Training/ Learning Period Noelle L'etoile1 1 University of California-San Francisco

Sleep promotes plasticity and protection of the nervous system but its cellular mechanisms, the basic biological processes by which this counterintuitive state consolidates memory remains a mystery. The physical state of sleep, characterized by reduced locomotion, stereotypical posture, increased arousal threshold, and homeostatic response to deprivation, is conserved across phyla from cnidaria to chordates. We find that C. elegans also require sleep to consolidate memory. The role of sleep in memory consolidation poses a conundrum: memory is formed by changes in synapse strength resulting from their repeated use while sleep has been shown to downscale synapses. Moreover, how sleep affects specific synapses with known functions, within individual cells of a circuit that encode memories, remains unknown in any system. We are using the GRASP tools to probe changes in connectivity within the olfactory circuit as a function of sleep.

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Modulation of Aversive Chemical Responses via Colonization by Tyramine-Producing Bacteria Michael O'Donnell1, Pin-Hao Chao1, Piali Sengupta1 1 Brandeis University

C. elegans and bacteria exhibit a complex interdependent relationship in which bacteria can be food sources, pathogens, as well as commensal organisms. In the wild, the C. elegans intestine is commonly colonized by live bacteria, potentially exerting diverse effects on host physiology and metabolism. Although C. elegans avoids strongly pathogenic bacteria through associative learning and chemosensory responses, it is unknown whether colonization by commensal or mildly pathogenic bacteria alters C. elegans behaviors. We find that colonization of the gut by a nematode-associated bacterial genera, Providencia (Ps), reduces chemosensory avoidance by C. elegans of long chain alcohols such as octanol as well as osmotic barriers. Previous studies have shown that aversive responses to octanol are modulated via the biogenic amines tyramine (TA) and octopamine (OA). TA is produced from its precursor tyrosine by the TDC-1 tyrosine decarboxylase; subsequently, TA is converted to OA via the TBH-1 tyramine betahydroxylase. Unexpectedly, while modulation of Ps-dependent octanol avoidance requires the ASH-expressed OA receptor OCTR-1, this modulation occurs independently of hostderived TA and the host tdc-1 enzyme. Instead, we show that Ps and other closely-related Enterobacteriaceae encode a functional tdc gene which appears to complement loss-offunction of host tdc-1. This bacteria-derived TA is likely to be converted to OA using the host TBH-1 enzyme. Our results suggest that commensal bacteria may co-opt neuromodulators to alter host behaviors upon gut colonization. We speculate that these bacteria-driven changes in host chemosensory behavior may drive distribution of these microbes in the host niche.

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Protein Arginine Methylation Regulation of the C. elegans SER2 Tyramine Receptor Alexander Bowitch1, Kerry L. Michaels1, Michael C. Yu1, Denise M. Ferkey1 1 University at Buffalo

Protein arginine methylation regulates numerous cellular functions, including proteinprotein interactions, gene expression, and the DNA damage response. Our lab previously reported the D2-like dopamine receptors as the first GPCR to be regulated by arginine methylation, where methylation of arginine residues within the third intracellular loop of human D2 (and C. elegans DOP-3) enhanced receptor signaling. We have identified a similar putative methylation motif in the C. elegans SER-2 tyramine receptor. Signaling through SER-2 modulates numerous C. elegans behaviors, including foraging behavior, threat avoidance, and pharyngeal pumping. We show that arginines within the third intracellular loop of the SER-2 receptor are methylated by the protein arginine methyltransferase PRMT-5, and that, similar to the D2-like dopamine receptors, methylation also enhances SER-2 receptor signaling. This work provides the second example of a GPCR regulated by protein arginine methylation and, consistent with our bioinformatics analysis, suggests that this post-translational modification may regulate GPCR signaling more broadly.

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PDFR-1 Signaling and Genetic Sex Intersect to Modulate Behavioral Responses to Sex Pheromone Jintao Luo1, Kelli A. Fagan1, Douglas S. Portman1 1 Department of Biomedical Genetics, University of Rochester

The mechanisms by which neural circuits integrate multiple dimensions of internal state to generate behavioral plasticity is poorly understood. Chemosensory responses to ascaroside sex pheromones offer an ideal opportunity to approach this problem. These responses depend on biological sex, a key dimension of internal state, but are also influenced by other factors. In previous work, we have shown that male attraction to ascarosides requires the sexual state of the shared ADF sensory neuron. In males, ADF responds to ascarosides and promotes attraction, but in hermaphrodites, this neuron is insensitive to ascarosides, allowing an innate weak repulsion to dominate. Genetic sex reversal of ADF alone is sufficient to reverse these behavioral responses. Recently, we have found that the conserved neuropeptide receptor PDFR-1 influences pheromone responses in both males and hermaphrodites. In males, loss of pdfr-1 severely compromises ascaroside attraction; however, in hermaphrodites, pdfr-1 loss strongly enhances repulsion. Ablation of ADF in pdfr-1 mutant males recapitulates this strong repulsion, indicating that PDFR-1 acts in parallel to genetic sex by suppressing a repulsive drive present in both sexes. Our preliminary results suggest that this repulsion is not mediated through ADL, a shared sensory neuron previously implicated in ascaroside aversion in hermaphrodites. Because pdfr-1 signaling also influences transitions between roaming and dwelling behavior, the increased dwelling behavior of pdfr-1 mutants might desensitize males to attraction but also sensitize hermaphrodites to repulsion. Together, these results illustrate a mechanism by which genetic sex and peptidergic signaling intersect to modulate chemosensory behavior.

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Electrical Synapses as Modulators of Neural Activity Lisa Voelker1,2, Ithai Rabinowitch1, Jihong Bai1,2 1 Fred Hutch Cancer Research Center, 2University of Washington

An animal must constantly adjust its behavior in order to respond to changing environments and fluctuations in internal states. Animals achieve this by altering neural activity levels through changes known as neural plasticity. While much research has focused on understanding changes that occur at chemical synapses, it is becoming clear that electrical synapses also have important roles to play. Electrical synapses are specialized sites of cytoplasmic communication between neurons and are known to coordinate local electrical activity and to pass the small molecules associated with neural plasticity. In C. elegans, electrical synapses are known to coordinate inputs from multiple different sensory modalities to influence behavior. I have shown that an electrical synapse between the primary quinine sensory neuron ASH and its neighbor ASK is required for modulation of the quinine response. This synapse is likely composed of the innexins INX18 and INX-19. The behavior is also modulated by mutations in the cGMP generating guanylyl cyclase GCY-27, which is not expressed within ASH. This suggests that the ASK/ASH electrical synapse is passing cGMP as a means of modulating neural activity and thus behavior.

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Small Peptide Mediated Self-Recognition Prevents Cannibalism in Predatory Nematodes James W Lightfoot1, Martin Wilecki1, Ralf J Sommer1 1 Max Planck Institute for Developmental Biology

Self-recognition is observed abundantly throughout the natural world regulating diverse biological processes. Although ubiquitous, often little is known about the associated molecular mechanisms and despite the prevalence of nematodes in nearly every ecological niche and the pre-eminence of Caenorhabditis elegans as a model organism, evidence of self-recognition behaviour has thus far never been described in nematodes. Here we investigate the predatory nematode Pristionchus pacificus and through interactions with its prey, reveal a self-recognition mechanism acting on the nematode surface, capable of distinguishing self-progeny from even closely related strains. We identified a key component of the self-recognition machinery located within a region of minimal recombination activity and as such developed a novel method of inducing informative recombination events via CRISPR/Cas9. Using this system, we have successfully identified the small peptide SELF-1 as a major component of self-recognition, which is expressed in all hypodermal cells at all stages of the life-cycle. SELF-1 is composed of an invariant domain and a hyper-variable C-terminus. A comparative analysis of this region revealed extreme variability in sequence, length and also self-1 copy number with disruptions to the hyper-variable region including even a single amino acid substitution sufficient to eliminate protection from predation. Furthermore, as the pharyngeal and nose sensory connectome are established in P. pacificus, it is now possible to investigate the interface between the self-recognition signal and the neural circuitry behind this behaviour. Thus, the selfrecognition system identified in P. pacificus enables this nematode to avoid cannibalism, while promoting the killing of competing nematodes.

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An Evolutionarily Ancient Neuropeptide System Molulates Aversive Gustatory Learning in Caenorhabditis elegans Katleen Peymen1, Jan Watteyne1, Elien Van Sinay1, Isabel Beets1, Liliane Schoofs1 1 Functional Genomics and Proteomics, Department of Biology, KU Leuven

Learning and memory are crucial processes that have been under intense investigation for many decades as they endow behavioural flexibility, enabling animals to adjust their behaviour based on previous experiences and the environment. Neuropeptides, an evolutionarily ancient and diverse class of neural messengers that are key regulators of animal physiology, are also emerging as important modulators of learned behaviours. However, little is known about how they modify learning and memory circuits. By screening neuropeptide receptor mutants in gustatory associative learning paradigms we found that a G-protein coupled receptor and its neuropeptide ligands, belonging to the evolutionarily conserved MyoInhibitory Peptide (MIP)-family, modify salt chemotaxis behaviour in light of recent experience. MIP signaling through the MIP receptor ortholog SPRR-2 is required for short-term gustatory plasticity as well as for aversive, but not appetitive, salt avoidance learning. Furthermore, MIP-mediated salt avoidance learning appears to depend on transcription and translation, thereby displaying hallmarks of long-term memory. These findings pave the way to investigate the orphan and poorly characterized orthologous MIP receptors in deuterostomians for a possible role in learning.

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C. elegans Learning and Decision Making in T-shaped Mazes Eleni Gourgou1,2, Kavya Adiga3,4, Ao-Lin Allen Hsu2,5 1 Mechanical Engineering, University of Michigan, 2Internal Medicine, Division of Geriatric and Palliative Medicine, Medical School, University of Michigan, 3Molecular, Cellular, and Developmental Biology, University of Michigan, 4Anthropology, University of Michigan, 5Molecular and Integrative Physiology, University of Michigan

Broadly supported findings illustrate C. elegans ability to exhibit associative, nonassociative and imprinted memory in the context of chemical stimuli. Here we demonstrate that C. elegans nematodes are capable of learning related to navigation in a structured environment (maze). We use 3D-printing technology to build the custom-made Worm-Maze platform, a novel and versatile behavioral arena. We show that C. elegans young adults can locate food in T-shaped mazes and they can learn which way to turn to find it again, after a single training session. Results indicate that learning experience is sufficient to introduce bias in the decision-making process, even in the presence of conflicting environmental cues. We provide evidence that C. elegans successful navigation in the maze requires tactile input and propriosensation, and that learning depends on chemosensation and mechanosensation. We also show that CREB-like transcription factor and dopamine signaling pathway are involved. C. elegans learning in the maze environment shares certain properties with the working memory mechanism. This is the first time that navigation-related learning is established and characterized in C. elegans, and the underlying mechanism is explored.

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Quantitative Phenotyping and Modeling Identifies Key Behavioral Rules Underlying C. elegans Aggregation Siyu Serena Ding1,2, Linus J Schumacher3,4, Robert G Endres3,4, Andre EX Brown1,2 1 Institute of Clinical Sciences, Imperial College, 2MRC London Institute of Medical Sciences, 3 Department of Life Sciences, Imperial College, 4Centre for Integrative Systems Biology and Bioinformatics, Imperial College

In complex biological systems, simple individual-level behavioral rules can give rise to emergent group-level behavior. While such collective behavior has been well studied in cells and larger organisms, the mesoscopic scale is less understood. Here, we investigate collective feeding in the roundworm C. elegans at this intermediate scale, and use quantitative phenotyping and agent-based modeling to identify behavioral rules underlying aggregation. We use fluorescent multi-worm tracking to quantify aggregation behavior in terms of individual dynamics and population-level statistics. Based on our quantification, we use agent-based simulations and approximate Bayesian inference to identify two key behavioral rules that give rise to stable aggregation, namely cluster-edge reversals and density-dependent switch between crawling speeds.

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Interaction of Oxidized ASNA-1 and ENPL-1(GRP94) in Neurons Promotes Insulin Secretion Agnieszka Podraza1, Balasubramanian Natarajan1, Dorota Robakowska1, Gautam Kao1, Peter Naredi1 1 Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg

ASNA-1 is a positive regulator of insulin secretion in C. elegans and mice and knock down in mice causes diabetes. To understand its biochemical role, we identified the chaperone ENPL-1 as a new positive regulator of insulin signaling that acts at the level of insulin availability similar to ASNA-1. DAF-28/insulin secretion is regulated by ENPL-1. ENPL-1 mutants do not secrete DAF-28::GFP while overexpression of ENPL-1 increases secretion. Using Y2H and GST pulldown analysis we showed that ENPL-1 binds to ASNA-1 through defined subdomains and IHC revealed that they co-localize in neurons. Coimmunoprecipitation studies showed that two proteins interact in neurons which are also one of the sites for insulin secretion. ASNA-1 is present in two states: oxidized and nonoxidized and a conversion is controlled via two redox-sensitive cysteines. Both states of ASNA-1 are present in neurons and ENPL-1 binds to oxidized ASNA-1. Consistent with mammalian findings that high ROS increases insulin secretion, high ROS conditions also increase DAF-28::GFP secretion, promotes oxidation of ASNA-1 and lead to more binding with ENPL-1. Moreover, binding between the two proteins requires DAF-28/insulin and decreases when insulin secretion is low. Preliminary data indicates that majority of the binding happens in ASI neurons that express DAF-28/insulin. We are now investigating the subcellular location of this interaction, hypothesizing that it might happen in Golgi or/and dense core vesicles. Taken together our findings provide molecular framework for how ROS promotes insulin secretion.

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Neuronal Control of Intestinal Metabolism Through ETS-5Mediated Insulin Signaling Ava Handley1, Roger Pocock1 1 Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University

Achieving energy homeostasis requires decision making at the molecular level – such as whether energy should be stored or used, and the behavioural level – such as the modifying food-search behavior. Integrating internal energy store information with external nutrient availability is essential for making these decisions. This integration is accomplished by the nervous system. We previously discovered that the transcription factor ETS-5 acts within the BAG/ASG neurons to control C. elegans intestinal fat levels and exploratory behaviour. Precisely how ETS-5 acts has yet to be elucidated; however, we have identified that neuropeptide secretion from the BAG neurons is an important component of the pathway. To identify potential ETS-5-regulated neuropeptides, we screened BAG-expressed neuropeptides for exploration defects. We identified that mutants for the insulin-like peptide INS-1 explore less and store more fat than wild-type, a similar phenotype to ETS-5 mutants. Our subsequent analysis found that ETS-5 regulates INS-1 expression in the BAG neurons, and that INS-1 can act specifically from the BAG neurons to control feeding behaviour. Our data reveal how external environmental signals and internal nutrient signals may be integrated through the nervous system to elicit changes to fat storage, and feeding behaviour. Juozaityte et al. (2017) The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety. PNAS

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The Mechanics and Biophysics of Getting in Touch Miriam Goodman1 1 Stanford University

Touch is the first sense to develop, the last to fade, and the least well understood of the five basic senses. Ion channels are the first responders of touch sensation—converting the mechanical energy delivered in a touch or the bend of a limb into neural signals. Yet, the identity of the proteins forming such channels remained elusive for decades. Research in my group and others has identified at least three classes of proteins that can form these so-called mechanoelectrical transduction (MeT) channels in mammals and invertebrates— DEG/ENaC sodium channels, TRP cation channels, and Piezo cation channels. We are working to expand our knowledge of how MeT channels depend on biophysics of force transfer for activation, and are continuing to identify the protein components of these channels. My talk will survey the current state of the field, describe tools for applying mechanical stimuli, and discuss results from our recent investigations combining genetics with analyses of biophysics of in vivo MeT channel activation in C. elegans.

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Shake ‘n Wake: Using Mechanosensory Stimulation to Probe Homeostatic Rebound during Stress-Induced Sleep Patrick McClanahan1, Ben Habermeyer1, Joyce Xu1, Anthony Ma1, Christopher Fang-Yen1 1 Department of Bioengineering, University of Pennsylvania

Sleep can be defined as a behavioral state with four characteristics: behavioral quiescence, increased arousal threshold, rapid reversibility, and homeostatic regulation. However, homeostatic regulation has not been demonstrated for all forms of sleep. Mammals exhibit three modes of sleep: PERIOD-regulated circadian sleep, cytokineinduced sickness sleep, and satiety-induced postprandial somnolence. Interruption of circadian sleep increases sleep drive, but it is unknown whether sickness and satietyinduced sleep are also under homeostatic regulation, and answering this question is complicated by the presence of PERIOD-regulated sleep. In C. elegans, the PERIOD homologue LIN-42 regulates developmentally-timed sleep (lethargus), and adult worms do not sleep under standard laboratory conditions, allowing other forms of sleep to be studied in isolation. Here we report the first observation of homeostatic rebound in non-PERIOD regulated sleep. To assay for homeostatic rebound in non-PERIOD regulated sleep, we used established protocols to induce satiety quiescence or stress-induced sleep in C. elegans adults and then interrupted quiescence using vibration provided by an audio loudspeaker. We found that brief interruptions in SIS resulted in periods of increased quiescence. We are undertaking both forward and candidate genetic screens for regulators of SIS homeostasis. We found no evidence of homeostatic rebound in satiety quiescence. Our findings suggest that homeostatic drive is a characteristic of stressinduced sleep in addition to circadian sleep, and may lead to insights into the regulation of sleep during recovery from illness and injury.

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Learning-Dependent Neural Gain Control by Asymmetric Modulation of First- and Second-Order Time-Differential of Stimulus in Sensory Neurons Yosuke Ikejiri1, Yuki Tanimoto1, Shuhei Yamazaki1, Kosuke Fujita1, Kotaro Kimura1,2 1 Osaka University, 2Nagoya City University

Animals respond to environmental stimuli whose intensity varies by approximately 10¹⁰fold, although neural responses can only change by 10²-fold, which requires proper adjustment of the relationship between environmental stimuli and neural response. One example of this adjustment is neural gain control, defined as change in the slope of a neural response to a stimulus, instead of a general reduction (adaptation) or enhancement (sensitization) of response. However, these mechanisms are poorly elucidated. Here, we report that neural gain control in ASH nociceptive neuron occurs by asymmetric modulation of first- and second-order time-differential of sensory stimulus. Previously, we showed that the worm’s avoidance behavior to the repulsive odor 2-nonanone is enhanced by preexposure to the odor as a type of non-associative learning (Kimura et al., 2010). Recently, we found that ASH responses, which are activated by increasing 2-nonanone concentrations (Tanimoto et al., 2017), are modulated by the odor learning. Quantitative odor stimuli analysis revealed that naive ASH neurons respond similarly to small and large linear increases in odor concentration, although pre-exposed ASH neurons only respond to large increases. Analysis of stimulus-response relationships suggested that this learningdependent change is a neural gain control of response. Interestingly, mathematical analysis revealed that the ASH response is approximated by the sum of first- and secondorder time-differential of odor concentration and learning modulates the contributions of each in a different manner. Our results suggest that quantitative sensory stimulus is key to revealing simple mechanisms underlying neural activity and their modulation by learning.

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Composition of Native Met Channels Responsible For Gentle Touch Sensation Sylvia Fechner1, LingXin Wang1, Frederic Loizeau1, Adam L Nekimken1, Isabel D’Alessandro2, Beth L Pruitt1, Miriam B Goodman1 1 Stanford University, 2Wellesley College

Touch receptor neurons (TRNs) of C. elegans are used as a system to understand the molecular events responsible for touch sensation. Key actors in this process include DEG/ENaC/ASIC proteins. These proteins form a mechano-electrical transduction (MeT) channel: MEC-4 is an essential, pore-forming subunit, MEC-10 is a non-essential, regulatory subunit. These two proteins are co-expressed with DEGT-1, another homologous protein. The presence of a third protein re-opens the question how those three proteins co-assemble to form the MeT channels in vivo. We are using a combination of behavioral assays, in vivo patch-clamp recording, and heterologous expression to investigate the contribution of DEGT-1 to touch and MeT channel formation. Classical touch assays revealed that degt-1;mec-10 double mutants have a more severe phenotype than degt-1 and mec-10 single mutants. With in vivo patchclamp recordings of native MeT currents activated by feedback-controlled mechanical stimulation, we identified a similar genetic enhancement: the maximal amplitude of the MeT currents was further reduced in degt-1;mec-10 double mutants than single mutants. Thus, DEGT-1 is likely a subunit of the native MeT-channel complex. To characterize DEGT-1-containing channels independent of the native tissue, we introduced the well-known d mutation and expressed DEGT-1d alone and in combination with MEC-4d in Xenopus oocytes. We found that DEGT-1d forms homomeric channels whose properties differ from those of MEC-4d. As found for MEC-10d, co-expressing DEGT-1d with MEC-4d decreased current amplitude compared to MEC-4d alone. Collectively, these results support the conclusion that DEGT-1, like MEC-10, plays a regulatory role in MeT channel formation and function.

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A Single Glia-Sensory Neuron Pair Interact through Multiple Molecular Mechanisms Aakanksha Singhvi1, Shai Shaham2 1 Fred Hutchinson Cancer Research Center, 2The Rockefeller University

The nervous system has two major cell types, neurons and glia, in about equal numbers. Glia interact closely with neurons and modulate their shape, functions and thereby animal behaviors. Glia also prune neuronal endings, correlated with maintenance of proper vision and neuronal connectivity. Molecular mechanisms underlying glia-neuron interactions remain poorly defined, especially in sensory systems. We previously showed that secreted Amphid-sheath glia (AMsh) cues maintain AFD thermo-sensory neuron-ending shape and thermotaxis behaviors. To identify these cues, we performed genetic screens and identified 11 mutants. Characterization of two mutants led to our uncovering a novel molecular mechanism by which glia modulate sensoryneuron shape and behaviors (Singhvi et al, Cell, 2016). Another mutant maps to the gene unc-23, a BAG2 Hsp co-chaperone that regulates protein folding. We found that unc-23 mutants exhibit progressive defects in shapes of AFD sensory neuron-endings, AMsh glia and anterior musculature, with abnormal vesicle accumulation in glia. Mutations in the E3-ubiquitin ligase CHN-1 cause thermo-sensory behavior defects and suppress unc-23 defects. Our molecular-genetic analyses thus far suggest that UNC-23 and CHN-1 may antagonistically regulate folding of glial protein(s) mediating AMsh-AFD glia-neuron interactions. Intriguingly, human Hsp gene mutations cause Charcot-Marie-Tooth disease with progressive glial defects and peripheral nerve degeneration. We also discovered that AMsh glia engulf AFD thermo-sensory neuron-ending fragments, establishing C. elegans as a powerful new model for glial pruning. We present preliminary characterization of engulfment defect mutants identified in our genetic screens. Together, our studies reveal that a single sense-organ glia-neuron pair interacts through multiple molecular mechanisms.

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Sensation, Circuits and Longevity: Lessons from the Worm Shawn Xu1 1 University of Michigan

Sensory cues not only regulate an animal’s behavior but also its physiology, for example, aging and longevity. In addition to nutrients, other environmental cues, such as thermoand chemo-sensory inputs, have a profound impact on aging and longevity. The nervous system plays a key role in mediating such effects. Here I will discuss our recent work on how sensory cues affect aging and longevity in C. elegans.

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Using Terminal Selector Transcriptional Targets and Differential Transcriptome Analysis to Identify Novel Regulators of Carbon Dioxide Sensing Mary Rossillo1, Niels Ringstad1 1 Skirball Institute, NYU School of Medicine

Chemosensitive areas of the mammalian brainstem regulate breathing and are stimulated by small increases in arterial carbon dioxide levels. The genetic and molecular bases for this type of chemosensitivity are poorly understood. The nematode C. elegans is an excellent model for determining mechanisms of sensing respiratory gases. This simple animal possesses a pair of CO₂-sensitive neurons - the BAG neurons - that mediate a stereotyped behavioral response to environmental CO₂ and whose cell physiology can be readily studied in vivo. Proper development of BAG neurons requires the ETS-domaincontaining transcription factor ETS-5, whose mammalian homolog is also required for the development and function of CO₂-chemosensitive neurons. To identify functionally important gene targets of ETS-5, we have performed a ChIP-seq study to identify loci occupied by ETS-5 followed by a behavioral screen for genes required for CO₂chemosensitivity. These studies have identified novel regulators of gas-sensing neurons and also provide a blueprint for gene discovery based on the molecular characterization of transcription factors required for the development and function of neurons with specialized physiology.

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Behavioral Valence to a Mating Cue is Regulated by a Neuropeptide Douglas K Reilly1, Emily J McGlame1, Haylea T Northcott1, Jagan Srinivasan1 1 Department of Biology and Biotechnology, Worcester Polytechnic Institute

Modulation of neural circuits is crucial for an animal’s survival, as they need to properly sense and react to a multitude of environmental factors. The nematode, Caenorhabditis elegans, employs a class of small molecule metabolites, ascarosides, to convey an array of information to conspecifics - including food and mate availability. The structure of ascarosides consists of a sugar and a fatty-acid chain which varies in length, saturation, and additional functional groups: small changes within any of these modules can alter the information relayed to conspecifics. A previously described spot retention assay showed that male C. elegans exhibit an increased dwell time in ascaroside #8 (ascr#8), improving their chances of locating the hermaphrodite that secreted the cue. However, this assay does not allow for qualitative parsing out of other behavioral phenotypes, due to its lack of sensitivity. We have developed a novel, single worm, behavioral assay which provides both quantitative and qualitative analyses of the effects of the ascaroside. Using this assay, we identified a previously unobserved phenotype for the neuropeptide, flp-3. flp-3 males do not exhibit increased dwell time in ascr#8, but instead avoid the cue. Interestingly, flp-3 hermaphrodites do not exhibit any defect in the avoidance behavior observed in wild-type animals. We propose that flp-3 controls the sex-specific valence of the attractive behavior of males to ascr#8. Our results support the notion that specific peptides encoded by flp-3 function within the male connectome to suppress a basal reversal response to ascr#8, thereby promoting attraction to the mating cue.

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A Critical Role for Thermosensation in Host Seeking by SkinPenetrating Nematodes Astra S. Bryant1, Felicitas Ruiz1, Spencer S. Gang2, Michelle L. Castelletto1, Jacqueline B. Lopez1, Elissa A. Hallem1,2 1 Department of Microbiology, Immunology, and Molecular Genetics, UCLA, 2Molecular Biology Institute, UCLA

Skin-penetrating parasitic nematodes are a major source of neglected tropical disease, infecting approximately one billion people primarily in the world’s most impoverished communities. Their life cycle includes an infective third-larval (iL3) stage that searches for hosts in a poorly understood process involving thermal and olfactory cues. We investigated the temperature-driven behaviors of skin-penetrating iL3s, including the human-parasitic threadworm Strongyloides stercoralis and hookworm Ancylostoma ceylanicum. We found that skin-penetrating iL3s are extremely sensitive to thermal gradients. Moreover, they show two distinct modes of temperature-driven movement, and the switch between them is subject to experience-dependent plasticity. At temperatures above their cultivation temperature (Tc), iL3s display robust thermophilic trajectories, moving toward temperatures approximating mammalian body temperature (Th). At temperatures below Tc, iL3s display cryophilic migration. Experience-dependent thermal plasticity occurs on a timescale similar to that of Caenorhabditis elegans thermal plasticity: within hours, exposure to a new Tc alters the thermal switch point between these diametrically opposed behaviors. Thermal plasticity may enable iL3s to optimize host seeking on a diurnal cycle, a possibility with important implications for the development of preventative interventions. Temperaturedriven responses are dominant in multisensory contexts; at temperatures below Th, iL3s appear to prioritize temperature-driven behaviors while suppressing chemosensory responses. Finally, targeted mutagenesis of the S. stercoralis tax-4 homolog abolishes heat seeking, suggesting that heat seeking is generated through an adaptation of molecular cascades that in C. elegans produce thermotaxis behaviors. Together, our results provide insight into the behavioral strategies and molecular mechanisms that allow skin-penetrating nematodes to target human hosts.

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cGMP-Dependent Signaling Regulates daf-7 Expression in the ASJ Neurons in Response to Bacterial Metabolites Jaeseok Park1, Joshua D. Meisel1, Dennis H. Kim1 1 Massachusetts Institute of Technology

Caenorhabditis elegans navigates through a microbial environment replete with metabolites produced by both nutritious and pathogenic bacteria. Previously, we showed that C. elegans respond to specific secondary bacterial metabolites from the pathogen Pseudomonas aeruginosa by changing the expression pattern of daf-7, a TGF-beta ligand, which in turn promotes behavioral avoidance of P. aeruginosa. From the characterization of mutants defective for this ASJ transcriptional response to P. aeruginosa, we have identified a requirement for a cGMP signaling pathway which require both a cyclic-nucleotide gated channel subunit, CNG-2(Cyclic Nucleotide-Gated-2), and a cGMP-dependent kinase (PKG), EGL-4. CNG-2 is required for daf-7 to be expressed in ASJ in response to P. aeruginsa exposure, and while wild-type animals show a robust influx of calcium in the ASJ neurons when exposed to P. aeruginosa metabolites, cng-2 mutants are defective in this calcium response. EGL-4 is a PKG that is also required for a regular daf-7 response to P. aeruginosa, but in contrast to cng-2 mutants, egl-4 mutants have a wild type calcium response to P. aeruginosa metabolites. Taken together, our data point to parallel cGMPdependent signaling pathways that activate daf-7 transcription in response to P. aeruginosa metabolites. Our findings underscore the multiple roles of cGMP in rapid transcriptional responses to environmental stimuli.

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Identification of Attractive Odorants Released by Preferred Bacterial Food Found in the Natural Habitats of C. elegans Elizabeth E. Glater3, Soleil E. Worthy1, Lillian Haynes2, Melissa Chambers3, Danika Bethune3, Emily Kan3, Kevin Chung3, Ryan Ota3, Charles J. Taylor1 1 Chemistry Department, Pomona College, 2Biology Department, Harvey Mudd College, 3 Neuroscience Department, Pomona College

In order to survive, organisms must detect appropriate food sources and avoid harmful ones. C. elegans uses chemosensation to distinguish among various species of bacteria, their major food source. However, less is known about what specific chemical cues C. elegans uses to detect and recognize different microbes. Previously, we examined the strong innate attraction of C. elegans for the odor of the pathogenic bacterium, Serratia marcescens and found that two odorants, acetone and 2-butanone, represent the more complex odor bouquet of S. marcescens (Worthy et al., Chem Sens 2018). This attraction likely facilitates ingestion and infection of the host C. elegans. Now, we are examining the food preferences of C. elegans for non-pathogenic bacteria isolated from its natural environment (Samuel et al., PNAS 2016) as well as the chemical basis of this attraction. We found that C. elegans showed a strong preference for four of the eight tested bacterial isolates over its standard food source, E. coli. Using solid-phase microextraction and gas chromatography coupled with mass spectrometry, we found that three attractive bacterial isolates (Alcaligenes sp. JUb4, Providenica sp. JUb5, and Providencia sp. JUb39) released isoamyl alcohol, a well-studied C. elegans attractant. Thus, isoamyl alcohol is likely an ethologically relevant odor that is released by some attractive bacterial isolates in the natural environment of C. elegans. Although bacterial-released volatiles have long been known to be attractive to C. elegans, our work is beginning to define specific volatile cues that represent particular bacteria to C. elegans.

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Conserved Mechanisms Underlie Sleep and Neurodegeneration Anne Hart1 1 Brown University

There is deep conservation across animal species in the genes and mechanisms critical for neuronal function and behavior. My research group takes advantage of this conservation and the strengths of C. elegans as a model organism to delineate underlying mechanisms in two different areas: sleep and motor neuron disease. In our work on sleep, we use classical forward genetic screens to identify genes required for sleep during C. elegans lethargus. And, we work collaboratively with researchers studying humans to identify additional conserved genes and pathways involved in sleep and the response to inadequate sleep. In our work on motor neuron diseases, we focus on identifying and understanding genetic modifiers SMA and ALS,- as understanding these modifiers should shed light on pathogenic mechanisms. We have generated C. elegans single copy/knock-in models of ALS by inserting patient alleles into the appropriate C. elegans gene. Currently, we are working collaboratively with researchers using similar knock-in models to identify conserved genetic modifiers and to understand why neurons degenerate and die in motor neuron diseases.

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sel-12 Mutations Deregulate Mitochondrial Ca2+ Homeostasis Causing Oxidative Stress Mediated Neurodegeneration in Caenorhabditis elegans Shaarika Sarasija1, Kenneth R. Norman1 1 Albany Medical College

Neurodegeneration is often characterized by mitochondrial dysfunction and metabolic deregulation. Mutations in the presenilin (PSEN) encoding genes (PSEN1 and PSEN2) cause most cases of familial Alzheimer’s disease (AD); however, the underlying mechanism of pathogenesis remains unclear. Here, we show that mutations in sel-12, the C. elegans gene encoding a PSEN homolog, result in mitochondrial metabolic defects that promote neurodegeneration as a result of oxidative stress. In sel-12 mutants, elevated endoplasmic reticulum (ER)-mitochondrial Ca2+ signaling leads to an increase in mitochondrial Ca2+ content which stimulates mitochondrial respiration resulting in an increase in mitochondrial superoxide production. By reducing ER Ca2+ release, mitochondrial Ca2+ uptake or mitochondrial superoxides in sel-12 mutants, we demonstrate rescue of the mitochondrial metabolic defects and prevent neurodegeneration. Interestingly, we observe that these phenotypes are independent of SEL-12’s role as a component of the gamma-secretase complex. These data suggest that mutations in PSEN alter mitochondrial metabolic function via ER to mitochondrial Ca 2+ signaling and provide insight for alternative targets for treating neurodegenerative diseases.

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The Role of Branched-Chain Amino Acid Transferase 1 in Parkinson’s Disease, Aging, and Longevity Danielle E. Mor1, Rachel Kaletsky1, Will Keyes1, Salman Sohrabi1, Coleen T. Murphy1 1 Princeton University

Parkinson’s disease (PD) is increasingly recognized as a multi-system disorder, characterized by both motor and non-motor symptoms including dementia. While the loss of dopaminergic neurons in the substantia nigra is a well-established source of motor disability in PD, the role of cholinergic degeneration in the disease remains relatively unexplored. The mechanisms that induce neurodegeneration in PD are still poorly understood, and over 70% of cases have no known cause. Using a new method we created that combines human genome-wide association studies with tissue-specific functional networks in C. elegans, we discovered a novel link between branched-chain amino acid transferase 1 (bcat-1), which catalyzes the first step in branched-chain amino acid (BCAA) catabolism, and PD. We found that BCAT-1 expression is normally high in PD-susceptible brain regions, and is reduced in the substantia nigra of PD patients. Reduction of neuronal bcat-1 in C. elegans caused an age-dependent, abnormal curling motor defect, and associated degeneration of cholinergic neurons. Dopaminergic neurons also degenerated with bcat-1 reduction, whereas mechanosensory neurons, which are not affected in PD, remained intact. Preliminary data suggest that loss of bcat-1 also causes memory impairment. Paradoxically, while our findings link bcat-1 knockdown to neurodegeneration and functional decline, reducing bcat-1 or elevating BCAAs greatly lengthens lifespan in yeast, worms, and mice. Simply extending lifespan is therefore insufficient for maintaining quality of life with age. Identifying the mechanisms by which BCAA metabolism regulates lifespan and neuronal health may suggest new targets for disease-modifying therapies and interventions that promote longevity without sacrificing brain function.

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EFF-1 Fusogen Promotes Phagosome Sealing during Cell Process Clearance Piya Ghose1, Alina Rashid1, Peter Insley1, Anupriya Singhal1, Meera Trivedi1, Pavak Shah2, Yun Lu1, Zhirong Bao2, Shai Shaham1 1 The Rockefeller University, 2.Developmental Biology Program, Sloan Kettering Institute

Programmed cell death and cell process pruning are common in development and homeostasis. Dismantling of cells with long processes, such as neurons, poses an interesting problem, as different regions of a cell are often in different microenvironments. The C. elegans tail-spike cell (TSC) extends a process during embryonic morphogenesis and then dies. Still images and long-term light-sheet microscopy reveal that the TSC undergoes three distinct degenerative events. The proximal TSC process is dismantled first, and undergoes Wallerian degeneration-like beading. The cell soma dies and is cleared similar to other apoptotic cells. The distal process retracts and accumulates in a varicosity. All three mechanisms depend independently on CED-3/caspase. Importantly, a similar sequence accompanies the demise of embryonic and sexually dimorphic CEM neurons. Thus, the TSC death program may represent a general mechanism for dismantling complex cells, including neurons. Clearance of the process is independent of known apoptotic engulfment proteins. We identified a mutant with a lesion in eff-1, encoding a fusogen, which is defective in TSC distal process varicosity clearance specifically. EFF-1 is expressed in and functions in the engulfing cell for the TSC process. While the remnant is recognized in eff-1 mutants, the phagosome remains open. EFF-1 also localizes to phagosome arms tips. Thus, EFF-1 may mediate the fusion event required for phagosome sealing. Direct mediators of membrane scission promoting phagosomes formation are not known. Our data reveal a novel paradigm for complex cell dismantling that may be broadly conserved, and suggest a novel role for EFF-1 in phagosome sealing.

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The Function and Dynamics of Autophagy in C. elegans Axon Regeneration Lizhen Chen1, Su Hyuk Ko1 1 UT Health Science Center

Autophagy is essential for maintaining cellular homeostasis by degradation of organelles or proteins, but its role in neuronal response to axon injury and subsequent axon regeneration remains largely unknown. We found that loss of function mutations in genes involved in the autophagy pathway led to impaired axon regeneration, which could be rescued by neuronspecific transgenic expression of the lost genes, suggesting a cell-autonomous role. Using a touch neuron-specific tandem-tagged mCherry-GFP-LGG-1 reporter that monitors isolation membrane/autophagosome and autolysosomes, we were able to study the dynamics of autophagy during PLM axon regeneration. In response to axon injury, there was a significant increase of autophagic vesicles. This injury-activated autophagy was required for axon regeneration, as blocking autolysosome formation significantly inhibits axon regeneration. The injury-triggered autophagy activation and the capacity of axon regeneration undergo an age-dependent decline, and both of the declines were partially rescued by autophagy-activating agents, indicating the positive role of autophagy in promoting axon regeneration. We found that axon injury failed to activate autophagy in animals lacking DLK-1, a conserved regulator of axon regeneration that promotes retrograde injury signaling. Activating autophagy was able to partially bypass the requirement of DLK-1 in axon regeneration. Finally we identified a functional target of autophagy in axon regeneration by a candidate screen. We are currently confirming the regulatory role of autophagy in limiting this target protein. Our data suggest that DLKmediated injury signaling can activate autophagy, which promotes axon regeneration by degrading regeneration-inhibiting proteins.

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ADM-4 is a Novel Regulator of Axonal Fusion Xue Yan Ho1, Sean Coakley1, Massimo A. Hilliard1 1 Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland

Axonal damage, such as that observed in nerve and spinal cord injuries, interrupts the communication between a neuron and its target tissue. Functional recovery is achieved when the regenerating axon re-innervates its original target tissue and a connection is reestablished. However, despite progress in medicine, this goal is still out of reach. C. elegans, and other invertebrate species, have evolved a specific repair mechanism, known as axonal fusion, whereby the proximal axonal fragment (still attached to the cell body) regrows, reconnects and fuses with its own separated distal axonal fragment, reestablishing the original axonal tract and neuronal function. This represents an innovative and potentially highly-effective repair strategy. Using a candidate gene approach, and the PLM mechanosensory neurons as a model system, we have identified ADM-4 as a key regulator of axonal fusion. ADM-4 is a member of the ADAM (A Disintegrin and Metalloprotease) family and the ortholog of the human ADAM17/TACE (Tumor necrosis factor Alpha-Converting Enzyme). Loss of ADM-4 leads to severe reduction of axonal fusion in PLM neurons without affecting axonal regrowth. ADM-4 is expressed in many tissues, such as the pharynx, hypodermis, vulva and neurons. We demonstrate that ADM4 regulates axonal fusion by functioning cell-autonomously in PLM neurons. We propose that its catalytic function is essential to regulate the fusion machinery. Our discovery of the role of ADM-4 in regulating axonal fusion provides new insights into how intrinsic molecules regulate axonal repair, and offers a strong foundation for designing novel therapeutics for injuries to the nervous system.

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An Epidermal Immune Signaling Network Regulates Antimicrobial Peptide-Mediated Dendrite Degeneration in Aging Lezi E1, Ting Zhou1, Sehwon Koh2, Marian Chuang3, Ruchira Sharma1, Nathalie Pujol4, Andrew Chisholm3, Cagla Eroglu2,5, Hiroaki Matsunami1,5, Dong Yan1,5 1 Department of Molecular Genetics and Microbiology, Duke University, 2Department of Cell Biology, Duke University, 3Section of Neurobiology and Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, 4Centre d’Immunologie de MarseilleLuminy, CIML, Aix Marseille Université, Inserm, CNRS, 5Department of Neurobiology and Duke Institute for Brain Sciences, Duke University

There is an emerging concept that the degeneration of neurons can be regulated non-cellautonomously by surrounding cells, such as astrocytes and microglia in mammals. However, it is unclear whether and how aging affects these surrounding cells to trigger neurodegeneration. Previously, we revealed an unexpected role of an epidermallyexpressed antimicrobial peptide, NLP-29 (neuropeptide-like protein 29), in triggering agingassociated dendrite degeneration in C. elegans. We also identified an orphan G proteincoupled receptor NPR-12 (neuropeptide receptor 12) acting in neurons as a receptor for NLP-29, and demonstrated that the autophagic machinery was involved cell-autonomously downstream of NPR-12 to transduce degeneration signals. These findings reveal an important causative role of non-neuronal antimicrobial peptides, their neuronal receptors and the autophagy pathway in aging-associated dendrite degeneration. Here, we further show that the age-dependent increase of nlp-29 expression in the epidermis is regulated by NIPI-3/tribbles and DAPK-1/death-associated protein kinase 1, with the involvement of TIR-1/SARM –PMK-1/p38 MAPK innate immune signaling pathway. Overexpressing positive or negative regulators of nlp-29, namely, nipi-3 or dapk-1, can manipulate the onset time of dendrite degeneration. We therefore propose that the aging-associated imbalance of such non-neuronal immune signaling networks functions as a trigger for antimicrobial peptide-mediated dendrite degeneration.

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Oral Talk #66

Small Molecule Modulators of sig2R/Tmem97 Reduce Alcohol Withdrawal-Induced Behaviors Luisa L Scott1, James Sahn1, Antonio Ferragud2, Rachel Yen1, Praveen Satarasinghe1, Michael Wood1, Timothy Hodges1, Ted Shi1, Brooke Prakash1, Kaitlyn Friese1, Angela Shen1, Valentina Sabino2, Stephen Martin1, Jonathan Pierce1 1 University of Texas at Austin, 2Boston University School of Medicine

Alcohol use disorder is a major public health problem. Repeated cycles of intoxication and withdrawal enhance the negative reinforcing properties of alcohol and lead to neuroadaptations that underlie withdrawal symptoms driving alcohol dependence. Pharmacotherapies that target these neuroadaptations may help break the cycle of dependence. The sigma-1 receptor (σ1R) subtype has attracted interest as a possible modulator of the rewarding and reinforcing effects of alcohol. However, whether the sigma2 receptor, recently cloned and identified as transmembrane protein 97 (σ2R/TMEM97), plays a role in alcohol-related behaviors remained unknown. Using a Caenorhabditis elegans model of alcohol withdrawal, we identified two novel, selective σ2R/Tmem97 modulators that reduced behavioral impairment following withdrawal from chronic alcohol treatment. The activity of these compounds was dependent upon the putative worm TMEM97 ortholog, Y38H6C.16, and could be rescued by substitution with the human TMEM97 gene. Further, σ2R/Tmem97 modulator activity was also dependent upon vem-1, the worm ortholog of the σ2R/TMEM97 protein partner, the progesterone receptor membrane component 1. Validating the predictive power of C. elegans, we then showed that one of these compounds blunted withdrawal-induced excessive alcohol drinking in a well-established rodent model of alcohol dependence. This finding supports the future use of alcohol withdrawal in C. elegans to predict treatments for alcohol consumption in mammals. Together, these discoveries provided the first evidence that σ2R/TMEM97 function modulates the behavioral effects of chronic alcohol exposure and that this receptor is a potential new drug target for the treatment of alcohol use disorder.

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Stress: A Story of Insulin-like Peptides, Message Mobilization, and Survival Rashmi Chandra1, Lisa Li1, Zahabiya Husain1, Shashwat Mishra1, Joy Alcedo1 1 Department of Biological Sciences, Wayne State University

Chronic stress decreases survival and predisposes animals to neurological disorders. In C. elegans, stress perception can trigger entry into dauer and the removal of stress cues will induce exit from dauer. Previously, we showed that neural regulation of dauer entry and exit involves specific insulin-like peptides (ILPs) that signal from distinct sensory neurons. Notably, the ILP ins-6 promotes dauer exit by acting from the ASJ sensory neurons upon improvement of the environment. Recently, we find that ins-6 mRNA is specifically trafficked to ASJ axons upon dauer arrest and lost from the axons to reappear in cell bodies upon dauer exit. Importantly, we show that axonal ins-6 mRNA levels modulate the C. elegans ability to exit from dauer arrest into reproductive growth. Specifically, an increase in axonal ins-6 mRNA expedites exit from dauer, whereas a decrease in axonal ins-6 mRNA delays exit, even after exposure to optimal environments. Axonal ins-6 mRNA transport depends on both insulin signaling and specific kinesins, where the kinesin-2 motor protein OSM-3 acts in ASJ neurons to traffic ins-6 mRNA to the axons in dauers. Together our findings suggest that stress promotes axonal mRNA transport to prime the nervous system and facilitate the switch from stress to post-stress states.

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Clearance of Circulating Transthyretin Decreases Cell nonAutonomous Proteotoxicity in Caenorhabditis elegans Kayalvizhi Madhivanan1, Erin Greiner1, Miguel Alves-Ferreira1,2, Nirvan Rouzbeh1, Carlos Aguirre1, Johan Paulsson1, Justin Chapman3, Xin Jiang3, Felicia Ooi4, Carolina Lemos2, Andrew Dillin5, Veena Prahlad4, Jeffery Kelly6 1 Dept. of Molecular Medicine, The Scripps Research Institute, 2 Instituto de Biologia Molecular e Celular, 3Misfolding Diagnostics, 4Department of Biology, University of Iowa, 5Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, 6Department of Chemistry, The Scripps Research Institute

Cell non-autonomous mechanisms of neurodegeneration occur in the proteinopathies, but how neuronal toxicity is generated from misfolded proteins expressed in non-neuronal tissues, is unclear. Also, whether modulating protein aggregate levels at distal locales affects the degeneration of post-mitotic neurons, remains largely unknown. In the transthyretin (TTR) amyloidosis diseases, cell non-autonomous toxicity is the default mechanism, as TTR is primarily produced by the liver -which remains unaffected- but neurons are impaired. V30M TTR is the most common TTR mutation that results in Familial Amyloid Polyneuropathy (FAP), affecting pain-, thermo-sensation, and sensory-motor function of the extremities by unknown mechanisms. To date, neither mouse nor Drosophila TTR models have faithfully recapitulated the cell non-autonomous neuronal toxicity. We generated C. elegans models expressing human V30M TTR exclusively in the bodywall muscle, and showed that secreted V30M TTR resulted in cell non-autonomous neuronal proteotoxicity. We identified sensory neurons with defective morphology that led to nociception-sensing impairments. We further showed that sensory neurotoxicity was attenuated through TTR degradation by distal macrophage-like non-affected cells. Inhibition of this cell non-autonomous TTR degradation increased non-native oligomeric TTR aggregate load and enhanced cell non-autonomous neuronal dysfunction. Importantly, reducing TTR levels by RNAi treatment or kinetically stabilizing natively folded TTR with a small molecule lowered TTR aggregate load and reduced neurotoxicity. Our findings reveal a critical role for modulation of protein degradation in distal tissues and suggest that activation of autophagy or analogous lysosomal degradation mechanisms in these tissues should be considered as a strategy for treating the TTR amyloidoses.

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Understanding the Effects of Inter-Tissue UPR Signaling on Ageing and Proteostasis Rebecca Taylor1, Soudabeh Imanikia1, Ming Sheng1, Nesem Ozbey1 1 MRC Laboratory of Molecular Biology

Activation of cellular stress responses can extend longevity in C. elegans. One of these stress responses, the endoplasmic reticulum unfolded protein response (UPR), can increase lifespan when activated specifically within the nervous system of the worm, through an inter-tissue signaling pathway that communicates UPR activation between neurons and the intestine. We used tissue-specific transcriptomics to better understand how neurons use UPR activation to influence lifespan. Surprisingly, many of the genes differentially regulated in intestinal cells when the UPR is activated in this tissue through neuronal signalling are regulators of cellular metabolism, in particular lipid metabolism. Through GC-MS analysis, we have identified specific lipid changes that may underlie the effects of neuronal UPR activation on ageing and proteostasis throughout the animal. These results indicate that UPR signaling between neurons and the intestine affects longevity and proteostasis through changes in intestinal lipid metabolism, and suggest that this pathway may represent a promising therapeutic target for the treatment of metabolic and protein misfolding-based diseases.

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POSTER PRESENTATIONS

Poster Session I: Odd-Numbered, 8:30 – 10:30 PM, Tuesday, June 26 Poster Session II: Even-Numbered, 8:00 – 10:00 PM, Wednesday, June 27

Posters will be displayed for the entirety of the meeting. Please refer to the schedule for presentation times.

Poster set up begins at 12:00 PM Monday. Posters must be taken down by 10:00 PM Wednesday.


Poster #70 No Abstract Assigned

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C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior Poster #71

Acute-Stress Impairs Cytoprotective Mechanisms through Neural Inhibition of the Insulin Pathway Diego Rayes1,2, Maria Jose De Rosa2, Tania Veuthey2, Jeremy Florman1, Jeff Grant1, Gabriela Blanco2, Mark Alkema1, Natalia Anderson1, Jamie Donnelly2 1 UMass Medical School, 2Instituto de Investigaciones Bioquímicas de Bahía Blanca (CONICET), Universidad Nacional del Sur

Persistent activation of the “fight-or-flight” response accelerates aging and increases the susceptibility to disease. We show that repeated induction of the C. elegans flight response inhibits conserved cytoprotective mechanisms. This acute-stress response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the nuclear translocation of the DAF-16/FOXO transcription factor through the activation of an adrenergic-like receptor TYRA-3 in the intestine. In contrast, environmental long-term stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of FOXO-dependent cytoprotective genes. These findings demonstrate how a neural stress-hormone signaling provides a state-dependent neural switch between acute and long-term stress responses, and provide mechanistic insights how acute stress impairs cellular defensive systems.

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An Integrated Non-Vertebrate Drug Discovery Platform for Neurodegenerative Disease Karolina Chocian1, Nicolas Dallière1, Thomas Barratt1, Hannah Rhodes1, Julia Sherriff1, Pete Appleford1, Alison Woollard2 1 Chronos Therapeutics, 2Department of Biochemistry, University of Oxford

An increasingly ageing population brings with it the concomitant problem of a heightened prevalence of age-related diseases, such as Alzheimer’s and Parkinson’s, presenting a growing challenge to and burden on existing healthcare provision. Existing therapies have very poor efficacy, so there is a pressing need for the development of new drugs. Currently, two major hurdles in the development of new drugs are the complications associated with negative side-effects and the cost, time and ethical considerations of testing in animal models of neurodegenerative disease which may not necessarily be predictive of efficacy or safety. By current estimates, only 50% of new chemical entities entering preclinical safety testing will progress to human trials, of which 30% will encounter further safety issues that will cause their development to be halted. Clearly there is a need for coupling of drug screening in neurodegenerative disease models with early identification of toxicological issues, in an effort to reduce attrition of drug candidates at later stages of the drug development process. Our collaboration, between the University of Oxford and Chronos Therapeutics, focuses on the development of a harmonised array of C. elegans disease model strains representing the major neurodegenerative diseases affecting the ageing population. These models will be screened within an integrated drug-screening pipeline coupling drug efficacy with toxicity readouts, using standard motility assays as well as novel methodologies to monitor disease-associated phenotypes.

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Stress Leads to Neurodegeneration in Single-Copy Models of Amyotrophic Lateral Sclerosis in C. elegans Saba N. Baskoylu1, Katherine Yanagi1, Jill Yersak1, Patrick O'Hern1, Loraina Stinson1, Sarah Grosser1, Animesh Mahapatra1, Jeremy Lins1, Kelsey Schuch1, Anne C. Hart1 1 Brown University

Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative disorder marked by the progressive loss of glutamatergic and cholinergic motor neurons. Approximately 10% of ALS patients have a familial history of motor neuron disease. Mutations in more than 16 genes have been linked to familial ALS (fALS), including SOD1, TDP-43, FUS and C9ORF72. We hypothesize that mutations in these genes may lead to motor neuron death via one, or a few, pathways. To examine the impact of ALS-associated mutations in different genes, we generated single copy fALS knock-in models in Caenorhabditis elegans (C. elegans). We characterized the models using well-defined genetic, behavioral and pharmacological assays. Many of the models lead to disrupted synaptic signaling at the neuromuscular junction. Furthermore, exogenous stressors revealed or aggravated defects associated with fALS mutations. A subset of fALS mutations lead to stress-induced degeneration in glutamatergic neurons and cholinergic motor neurons. We are undertaking an unbiased forward genetic screen to identify suppressors of glutamatergic neurodegeneration in C. elegans. Over 50 suppressor lines have been identified; the next step is identification of suppressor genes. To complement the genetic screen, we conducted a comprehensive literature search for previously identified genetic modifiers of ALS-associated genes. We are using bioinformatic approaches to organize genetic modifiers into common pathways relevant to ALS. Our findings will be integrated with results from other ALS studies to understand how motor neurons die and to determine therapeutic pathways.

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Neuronal Somas Suffice for Morphofunctional Regeneration during Diapause in C. elegans Mauricio Caneo1, Mark Alkema2, Andrea Calixto1 1 Universidad Mayor, Center of Genomics and Bioinformatics, 2University of Massachusetts, Medical school

Neurons have an intrinsic capacity to grow during development and after damage. This ability to regrow after an insult depends on life stage, neuronal type, intrinsic and extrinsic factors. Here we show that diapause entry is a potent inductor of morphofunctional regeneration of neurons. C. elegans enters diapause under stresses of varied nature. We previously showed that in a degenerin model of neuronal degeneration (mec-4d mutation), which causes the unregulated entry of cations to the cell, and the energetic collapse of the mechanosensory neurons, diapause protected cells from degeneration. In mec-4d animals, embryonic touch receptor neurons die before hatching, while the AVM neuron is born at 12 hours posthatching, and, degenerates in a time-dependent manner with a stereotyped change in morphology. We examined the morphological and functional changes in individual AVMs in a longitudinal fashion during the first days in diapause. We focused on whether morphology at dauer entry influenced the outcome of regeneration after three days. Absence of soma precluded regrowth showing that AVMs cannot arise de novo if their somas have degenerated. The highest degree of regeneration was displayed by neurons with only a soma, even though broken axons of different lengths were also able to regrow. Probably dauer somas and their extracellular matrix may resemble a stem cell like environment where the extension of an axon occurs anew. Interestingly, the extent of axonal regrow was inversely proportional to the initial axon length at diapause entry, and once the axonal functionality was restored, the regeneration decreased.

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Possible Role of Tamalin/GRAS-1 in Bridging Glutamate & Insulin/IGF Signaling (IIS) Cascades in a Nematode Model of Excitotoxic Necrosis Ayesha Chowdhury1,2, Shavanie Pershad3, Teena Thomas1, Itzhak Mano1,2 1 Molecular, Cellular and Biomedical Sciences, The CUNY School of Medicine, Center for Discovery & Innovation, City College (CCNY), The City University of New York (CUNY), 2CUNY Neuroscience Collaborate Program, CUNY Graduate Center, 3Undergraduate Program in Biochemistry, CCNY, CUNY

Stroke, a leading cause of death and epidemiological disparities, is caused by overactivation of Glutamate Receptors (GluRs) leading to neurodegeneration via excitotoxicity. However, studies have shown that under excitotoxicity GluRs are also able to mediate neuroprotection. FoxO is a transcription factor that regulates cell stress resistance and has been primarily studied for its pro-apoptotic roles in other paradigms. We hypothesize that FoxO may be regulated by GluRs to mediate neuroprotection in excitotoxicity. To elucidate the connection between FoxO and GluRs, we use C. elegans, a powerful model system with simplified and conserved signaling pathways. We have previously shown that the Insulin/IGF Signaling (IIS) cascade, which inhibits FoxO/DAF-16 activity by withholding it from the nucleus, regulates neurodegeneration levels in a nematode model of excitotoxic necrosis (glt-3;nuIs5). We have also identified the Cytohesin/GRP-1 protein complex as an important upstream regulator of the IIS cascade in excitotoxicity. The scaffolding protein Tamalin/GRAS-1 may be an important link between GluRs and the IIS cascade via interactions with the Cytohesin/GRP-1 and GluRs. We propose that Tamalin/GRAS-1 is an upstream effector that regulates the IIS cascade in excitotoxicity and bridges the IIS cascade to the activity of GluRs through conformational interactions. I have shown that Tamalin/GRAS-1 regulates levels of neurodegeneration in excitotoxic necrosis via the IIS cascade. Preliminary results also suggest that the level of neurodegeneration in excitotoxic necrosis may correlate with DAF-16 nuclear localization. The outcome of this study will establish a novel neuroprotective pathway mediated via GluR regulation of FoxO/DAF-16 in excitotoxicity.

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Functional Study of Huntingtin using Caenorhabditis eleagans Christine Chung1, Hanee Lee1, Ihn Sik Seong2,3, Junho Lee1 1 Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, 2Center of Human Genetic Research, Massachusetts General Hospital, 3Department of Neurology, Harvard Medical School

The CAG expansion mutation in huntingtin (Htt) are predominantly found in patients suffering from neurodegenerative disorder Huntington’s disease (HD). Huntingtin is essential as it is required for normal development in many different eukaryotes. However, even with its critical role in the body, normal function of huntingtin is still in question. Our experimental results using Caenorhabditis elegans show Ce_Htt F21G4.6 putative role in stress response. Gene F21G4.6 is known ortholog of human huntingtin in C. elegans. According to sequence alignment analysis, F21G4.6 in C. elegans and huntingtin in human have very similar sequences especially near the C termini. Expression pattern analysis shows that F21G4.6 is expressed in specific subset of neurons that are closely related to stress responses in C. elegans. C. elegans with mutant F21G4.6 proteins are less tolerant of thermal stress than normal worms. The results indicate that F21G4.6 proteins in C. elegans take roles in stress response pathway. Genes having similar sequences to human huntingtin are commonly found in many other eukaryotes suggesting that huntingtin may share similar functions across different species. We are continuing our research by having different approaches to evaluate Ce_Htt stress response function which may lead to help find normal function of gene huntingtin in other species.

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Identification of Genetic Suppressors of smn-1 in Neurodegeneration Elia Di Schiavi1, Pamela Santonicola1, Ivan Gallotta1, Alessandro Esposito1, Giuseppina Zampi1 1 Institute of Bioscience and BioResources, CNR

Smn1 is the gene responsible for Spinal Muscular Atrophy (SMA), a devastating disease characterized by progressive degeneration and death of a specific subclass of motoneurons (MNs). The molecular mechanisms underlying the disease are not understood. The lethality associated with loss of function mutations in Smn1 has made the study of its function hard to investigate in any animal model. In C. elegans, the Smn1/smn1 mutants available present some limitations for manipulation and show no neurodegeneration (Briese et al., HMG, 2009; Sleigh et al., HMG, 2010). To overcome these limits and investigate the role of smn-1 specifically in the nervous system, we used a neuron-specific RNAi strategy to silence smn-1 selectively in the GABAergic MNs (Gallotta et al., HMG 2016; Esposito et al., Gene, 2007). These animals, viable and fertile, present an age-dependent degeneration of MNs that results in neuronal cell death and altered backward movements. The neurodegenerative phenotypes shown by the MNs silencing of smn-1 can be modulated by Smn1 interactors identified in other species, such as Plastin3/plst-1 and WDR79/tcab-1 (Gallotta et al., HMG 2016; Di Giorgio et al., Neurobiol Dis 2017). We are now using this model as a tool to identify, by forward and reverse genetics approaches, genes that interact with smn-1 and that once mutated fully rescue the degeneration. After excluding genes impairing the RNAi machinery or involved in apoptotic death execution, we are focussing on the genes fully protecting neuronal integrity and survival in early phases. We will present the most interesting ones.

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Food Perception through a Pair of Olfactory Neurons Triggers Rewiring of Organismal Proteostasis Fabian Finger1, Franziska Ottens1, Alexander Springhorn1, Tanja Drexel2, Lucie Proksch1, Sophia Metz1, Luisa Cochella2, Thorsten Hoppe1 1 Institute for Genetics and CECAD Research Center, University of Cologne, 2IMP-Research Institute of Molecular Pathology

The nematode C. elegans has a refined sensory system to integrate environmental changes into whole-animal behavior and physiology. It remains unknown how environmental perception impacts on integrity of the organismal proteome. To elucidate this fundamental attunement, we investigated the influence of bacterial food sources on protein quality control. Intriguingly, we identified an overriding role of a single pair of olfactory amphid wing C (AWC) neurons, which governs rewiring and arrangement of ubiquitin-dependent protein degradation pathways upon exposure to different bacterial strains. Neuron-type specific food perception is moderated by the microRNA mir-71, controling chemotaxis behavior, proteostasis, and lifespan through regulation of the toll and interleukin-1 receptor domain protein TIR-1. Olfactory inputs are further transduced from AWCs to peripheral tissues by vesicle secretion of neuropeptides. This work identified a neuronal circuit that rewires proteolytic networks in intestinal cells, establishing an underlying concept for the regulation of organismal food-adaptation.

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The Role of MANF in ER Stress Response in C. elegans Jessica Hartman1, Christopher Richie2,3, Priscila Castillo2, April Zhu2, Yun Wang2, Barry Hoffer2, Joel Meyer1, Brandon Harvey2 1 Duke University, 2National Institute on Drug Abuse, National Institutes of Health, 3Naitonal Institute on Diabetes, Digestive and Kidney Disorders, National Institutes of Health

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is the only human neurotrophic factor with an evolutionarily conserved C. elegans homologue, Y54G2A.23 or manf-1. MANF is a small, soluble, endoplasmic reticulum (ER)-resident protein that is secreted upon ER stress and promotes survival of target cells such as neurons. However, the mechanisms of how MANF modulates ER stress response and protects cells are still poorly understood. Moreover, the role of MANF in C. elegans is only beginning to emerge. In this study, we show that mutation of C. elegans causes a slight decrease in median lifespan (20 days vs. 21 days for N2, p

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