“THE WORM”

Caenorhabditis elegans as a model organism

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.

• Grown in large quantities in labs.

• Cultured on agar gel.

• Eats bacteria (E. coli).

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)

Anatomy

Experimental techniques• Microscopy

• Electrophysiology

• Calcium imaging

• Genetics...

• Reconstruction• Laser ablation

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

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.

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).

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).

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).

The locomotion system

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.

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.

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.

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.

MotorN.S.

Muscles

Body

SensoryNeurons

Environment

“Intentions”

Questions?