“THE WORM”

1. “THE WORM” Caenorhabditis elegans as a model organism

2. Caenorhabdi-what!?! • C. elegans is anematode round worm. • Very small (1mm). • Naturally found in damp soil and rotting fruit. • Two sexes: hermaphrodite and male.

3. Grown in large quantities in labs. • Cultured on agar gel. • Eats bacteria (E. coli).

4. Who’s cares about worms? • Excellent model organism for the study of: • Nervous systems* • Genetics (7K/20K genes shared with human. Fully sequenced) • Development (takes only 3 days, cell lineage tree is known)

5. Anatomy

6. Experimental techniques • Microscopy • Electrophysiology • Calcium imaging • Genetics...

7. Reconstruction • Laser ablation

8. The worm vs. larger animals • Nervous system size: • Neuron Complexity: • Neurons generally fire action potentials (“digital”). • The worm lacks the necessary ion channels, so the neurons do not spike. Instead, use graded potentials (“analogue”). 80,000 100,000,000,000 302

9. What we know about it • Nervous system: • Invariant, all neurons identified by name. • Individual synaptic connections are mapped. • Role of many neurons known from ablations. • Genetics: • Genome has been fully sequenced. • Single gene mutants with known locus & phenotype. • Development: • Full sequence of cell divisions from egg to adult (cell lineage) has been mapped.

10. C. elegans behaviour • Exhibits rich behaviours involving: • Multiple sensory modalities (touch, smell, temperature). • Learned associations (temperature and food preference). • Current internal state (e.g. hunger). • Locomotion* (central to all behaviours). • For example: • Collective social behaviour (aggregation on food). • Hunting food (if hungry). • Threat avoidance (physical and chemical). • Mating (male).

11. Locomotion • Worm crawls on surface while lying on its side. • Forwards motion with reversals and turns. • Exhibits sinusoidal body wave. • Forwards motion achieved by propagating body wave from head to tail. • Muscles only allow bending in 2D (dorsal / ventral).

12. Modelling locomotion, an interdisciplinary project • Our goal is to understand and model the worm’s forward locomotion. • This challenging project requires a group effort: • Experimental biology (genetic, behavioural, ablations). • Physics (mechanics of body/environment). • Engineering (mechanical experiments, robotics). • Computer science (data analysis, computational modelling).

13. The locomotion system

14. Minimum circuit • Identified by ablations. • One interneuron (AVB) provides “on” signal. • Gap junctions to fwd MNs: • 11 VB and 7 DB neurons • Few synaptic connections. • How are oscillations generated? • Stretch receptors sense body bending.

15. A simple model • Based on minimal circuit. • Divided into 11 segments. • Each contains two MNs. • All receive current input from AVB. • Receive stretch input from local and posterior segment. • Sensory feedback is key mechanism. • Dorsal and ventral neuron compete to control segment bending.

16. Gait adaptation • Worm locomotion generally studied on agar. • Gait is quite different when swimming in water. • Previous model can only reproduce crawling. • We wish to extend the model to both behaviours. • The gait change seems to depend on the changing “feel” of the environment.

17. Body and environment • Worm locomotion is unusually dependent on sensory feedback loop. • This is dependent on the environment properties. • The neural model needs an embodiment in order to adapt to model gait adaptation. • We therefore want a physical model of the worm and the environment. “Intentions” Motor N.S. Muscles Sensory Neurons Body Environment

18. Questions?