1. THE WORM Caenorhabditis elegans as a model organism

2. Caenorhabdi-what!?! C. elegans is a nematode 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. Whos 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). 100,000,000,000 80,000 302

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 worms 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. Motor N.S. Muscles Body Sensory Neurons Environment Intentions

18. Questions?