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Connectome to behaviour: modelling C. elegans at cellular resolution

Discussion meeting

Location

The Royal Society, London, 6-9 Carlton House Terrace, London, SW1Y 5AG

Overview

Scientific discussion meeting organised by Dr John White FRS, Dr Stephen Larson, Dr Andre Brown, Dr William Schafer and Professor Netta Cohen

Credits: Dr Stephen Larson, OpenWorm

It has been 30 years since the "mind of the worm" was published in Philosophical Transactions. Predicting C. elegans’ behaviour from its wiring diagram has been an enduring challenge since then. This meeting will bring together neuroscientists, physicists, and engineers to discuss advances in neural activity imaging, behaviour quantification, and multiscale simulations and how they are bringing the goal of whole-animal modelling at cellular resolution within reach.

The schedule of talks and speaker biographies are available below. Recorded audio of the presentations will be available on this page after the meeting has taken place. Meeting papers will be published in a future issue of Philosophical Transactions B.

Poster session

There will be a poster session on Monday 29 January. If you would like to apply to present a poster, please submit your proposed title, abstract (not more than 200 words and in third person), author list and affiliation, name of the proposed presenter and institution, with the subject line "Poster submission: C. elegans" to the Scientific Programmes team by Tuesday 2 January 2018. Please note that places are limited and are selected at the scientific organisers discretion. Poster abstracts will only be considered if the presenter is registered to attend the meeting

Attending the event

This meeting is intended for researchers in relevant fields.

  • Free to attend
  • Limited places, advanced registration is essential
  • An optional lunch can be purchased during registration

Enquires: Contact the Scientific Programmes team.

Event organisers

Select an organiser for more information

Schedule of talks

29 January

09:00-12:20

Biophysics of C. elegans behaviour

5 talks Show detail Hide detail

Chairs

Professor Netta Cohen, University of Leeds, UK

09:05-09:30 Connecting a connectome to behaviour: evolution and ensemble analysis of integrated neuromechanical models of C. elegans

Dr Eduardo Izquierdo, Indiana University, USA

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09:35-10:00

Dr Andre Brown, Imperial College London, UK

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10:05-10:30 Three-dimensional realistic model of the C. elegans body with elastic cuticle, hydrostatic pressure and muscle cells

Dr Andrey Palyanov, AP Ershov Institute of Informatics Systems, Siberian Branch of the Russian Academy of Sciences, Russia

Abstract

In order to better understand how a nervous system may control the movements of an organism, Dr Andrey Palyanov has created a three-dimensional simulated physical model of the C. elegans body. The body model is created with a particle-system-based simulation engine known as Sibernetic, which implements the smoothed particle hydrodynamics algorithm. The model includes a body-wall cuticle subject to hydrostatic pressure. This cuticle is then driven by body wall muscle cells whose positions and shape are derived from C. elegans anatomy, determined from light microscopy and electron micrograph data. Andrey shows that by using different muscle activation patterns, this model is capable of producing C. elegans-like behaviours, including crawling and swimming locomotion in environments with different viscosities while fitting multiple additional known biomechanical properties of the animal.

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10:35-11:05 Coffee

11:05-11:30

Professor Netta Cohen, University of Leeds, UK

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11:35-12:20 Panel discussion

12:20-13:15

Lunch

13:15-17:00

Structure and function of C. elegans nervous system

5 talks Show detail Hide detail

Chairs

Dr William Schafer, MRC Laboratory of Molecular Biology, UK

13:15-13:40 Ion channels: from literature to computational model

Dr Vahid Ghayoomie, The Openworm Foundation, USA

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13:45-14:10 The pan-neuronal regulator CMK-1 acts locally to enable flexible behaviours

Professor Miriam B Goodman, Stanford University, USA

Abstract

The ability to adapt behaviour to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. The behavioural repertoire of Caenorhabditis elegans nematodes includes several that are modulated by prior experience, including thermotaxis, mechanosensation, and chemotaxis. Work by Miriam's research group and others (e.g. Yu et al., 2014; Schild et al., 2014) has linked plasticity in many of these behaviours to a calcium and calmodulin-dependent kinase encoded by the cmk-1 gene. CMK-1 is the sole ortholog of mammalian CaMKI/IV. Despite the expression of CMK-1 in most, if not all of the 302 neurons that make up the hermaphrodite nervous system, CMK-1 seems to function cell-autonomously in primary sensory neurons to enable flexible behaviours. This presentation will review studies of CMK-1 function in the C. elegans nervous system as an entry point for considering the ways in which flexibility and experience shape behaviour.

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14:15-14:40 Developmental connectomics and circuit insights for rhythm generation

Professor Mei Zhen, Lunenfeld-Tanenbaum Research Institute and University of Toronto, Canada

Abstract

The ability of animals to generate goal oriented motor behaviors ensures their survival. Professor Mei Zhen will present results that begin to describe the molecular and cellular origins of motor rhythm in C. elegans. Through cell ablation, electrophysiology, and calcium imaging, Mei will show the following: 1) forward and reverse movements are driven by different oscillators; 2) the cholinergic and excitatory A class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive reverse movements without premotor interneurons; 3) the UNC-2 P/Q/N VGCC (voltage-activated calcium current) underlies A motor neuron’s oscillation; 4) the 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 determine the propensity and duration of reverse movements. Previously, Professor Zhen’s group and others showed that only the body wall muscles generate L-VGCC-dependent action potential bursts. Hence excitatory motor neurons themselves derive P/Q/N-VGCC-dependent oscillatory motor rhythms and body wall muscles control bursting; descending interneurons regulate their motor neuron activity to control the reversal motor state. Hence, the C. elegans locomotory behaviors are driven by a fundamentally conserved (CPG-driven), but anatomically compressed motor circuit. Mei proposes that functional compression, that a single neuron or neuron class adopt multiple roles when a nervous system constrained by cell numbers, is a property that allows small animals to serve as compact models to dissect the organizational logic of circuits.

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14:45-15:10 Whole-brain imaging with complete neural identity in freely-moving C. elegans

Dr Eviatar Yemini, University of Columbia, USA

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15:15-16:00 Panel discussion

15:15-15:45 Tea

30 January

09:00-12:45

21st Century digital and math tools for nervous system modelling

6 talks Show detail Hide detail

Chairs

Dr Stephen Larson, The OpenWorm Foundation, USA

09:00-09:25 Modelling neural activity of C. elegans nervous system

Dr Eli Shlizerman, University of Washington, USA

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09:30-09:55 Modelling the neural network of C. elegans at multiple scales with c302

Dr Padraig Gleeson, University College London, UK

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10:00-10:25 Taming complexity: controlling networks

Professor Albert-László Barabási, Northeastern University and Harvard Medical School, USA

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10:30-10:35 Geppetto - An open platform for biology data exploration, visualization and simulation

Mr Matteo Cantarelli, OpenWorm Foundation, USA

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11:00-11:30 Coffee

11:30-11:55 Reproducibility and rigour: testing the data driven model in C. elegans

Professor Sharon Crook, Arizona State University, USA

Abstract

Computational models provide a framework for integrating data across spatial scales and for exploring hypotheses about the mechanisms underlying neuronal and network dynamics. We have contributed to a successful system of interoperable, open source tools to address issues around creating, exchanging, and re-using models in neuroscience. In spite of this promising movement toward model sharing and reproducibility in the neuroscience community, it is extremely rare to see a specific, rigorous statement of the criteria used for evaluating models against experimental data. Another collaborative project from our group is providing a flexible infrastructure for assessing the scope and quality of models. The goal is to integrate experimental data with modeling efforts for more efficiency, better transparency, and greater impact of computational models in neuroscience research. We highlight examples of model validation from the C. elegans nervous system and also propose how hierarchical model validation, proceeding from the testing of small model components all the way to entire systems, can be used to systematically build a biologically-inspired model of an entire organism.

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12:00-12:45 Panel discussion

12:45-13:40

Lunch

13:40-17:00

Biological interpretations of nervous system modelling

5 talks Show detail Hide detail

Chairs

Dr John White FRS, University of Wisconsin, USA

13:40-14:05

14:10-14:35 Probing the structure and function of neuronal connectomes

Dr William Schafer, MRC Laboratory of Molecular Biology, UK

Abstract

The synaptic connectome of C. elegans has been mapped completely, and efforts are ongoing to map the connectomes of other animals. However, chemical synapses represent only one of several types of signaling interactions upon which the nervous system depends. In particular, neuromodulatory interactions involving monoamines, neuropeptides, or classical neurotransmitters are widespread in all nervous systems, and these interactions largely occur extrasynaptically between neurons unconnected by wired synapses. In C. elegans it is feasible to map these extrasynaptic networks comprehensively and at a single-cell level. We have compiled a draft extrasynaptic connectome for monoamine signaling, and in collaboration with others have begun mapping the extensive neuropeptide connectome. We are exploring the topologies of the neuromodulatory connectomes and their relationships with the wired synaptic and gap junction networks, as well as their functional roles in the control of behavioural states such as arousal. We are also developing approaches for behavioural analysis that can be used to probe the structure and function of both the synaptic and extrasynaptic networks. Further analysis of the C. elegans multilayer connectome should provide insight into how wired and wireless signaling interact in the brains of more complex animals.

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14:40-15:05 Creating formal interpretations of C.elegans nervous system dynamics

Dr Stephen Larson, The OpenWorm Foundation, USA

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15:10-15:40 Tea

15:40-16:05 Thirty years of the C.elegans connectome

Dr John White FRS, University of Wisconsin, USA

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16:10-17:00 Panel discussion