Transcript Jordan Boyle`s lecture

“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
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Microscopy
Electrophysiology
Calcium imaging
Genetics...
• Reconstruction
• Laser ablation
The worm vs. larger animals
• Nervous system size:
80,000
100,000,000,000
302
• 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”).
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:
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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:
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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:
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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
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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.
“Intentions”
Motor
N.S.
Muscles
Sensory
Neurons
Body
Environment
Questions?