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From gene to identified neuron to behaviour in Caenorhabditis elegans

Key Points

  • The advantages of Caenorhabditis elegans for studies of the genetics of behaviour include a fully sequenced and mapped genome, a complete anatomical map of the 302-cell nervous system and several well-described behaviours.

  • Because every neuron in C. elegans is known and has been anatomically described, it is easier to go from gene to identified neuron to behaviour than it is in an organism with a larger, more complex nervous system.

  • In C. elegans, numerous genes have been described, for which the null mutations produce very specific behavioural phenotypes.

  • Many techniques have been developed to study behaviour in C. elegans at several levels; for example, behavioural, neural-circuit and electrophysiological analyses, all of which can be combined with both forward and reverse genetic techniques.

  • Genetic analyses of C. elegans behaviour include behaviours such as feeding, egg laying, response to mechanical stimuli, learning and memory, and the effects of experience on development; all of these have led to new insights into how genes can influence behaviour.

  • The small, tractable nervous system of C. elegans, combined with the arsenal of genetic tools that can be applied to its study, offers a unique opportunity for researchers to address the difficult problem of finding the way from genes to neurons to behaviour.

Abstract

Understanding the role of genes in behaviour is greatly enhanced by understanding how they affect the function of the neurons that underlie behaviour. The study of behavioural genetics in Caenorhabditis elegans, an organism with a nervous system small enough to allow the role of every neuron in a given behaviour to be known, has given researchers unique insights into how genes contribute to behaviour in general. Many have taken advantage of the unique features of this worm to analyse genes from their sequence to their role in neuronal function and, ultimately, in behaviour.

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Figure 1: Neuron-specific transgenes.
Figure 2: Neuronal connectivity and gene expression in Caenorhabditis elegans.
Figure 3: Neuronal circuit that controls egg laying in Caenorhabditis elegans.
Figure 4: Neuronal circuit that controls forward and backward locomotion in the tap-withdrawal response.
Figure 5: Social variants in Caenorhabditis elegans.

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Acknowledgements

I thank J. Rose, S. Steidl, B. Ormerod, L. Galea, B. Christie and C. Thacker for reading earlier versions of this manuscript. I thank the C. elegans community for generously making room for researchers to discover the joys of working on C. elegans and for sharing knowledge, data, strains and ideas freely.

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DATABASES

LocusLink

RCNC2

VGLUT1

Wormbase

avr-15

cat-1

cat-4

daf-11

daf-21

eat-4

eat-6

egl-1

egl-19

gcy-5

glr-1

gpa-9

mec-4

npr-1

odr-10

osm-9

tax-2

tax-4

tpa-1

tph-1

unc-6

unc-36

unc-47

FURTHER INFORMATION

C. elegans II

C. elegans community server

Wormbase

C. elegans Genetics Center

C. elegans Genome Project

C. elegans Knockout Consortium

Center for C. elegans anatomy

Comprehensive Protocol Collection – Ambros lab

DNA microarray site

Expression Pattern Database

Lockery Site – data on GFP expression patterns

Glossary

PHARYNGEAL PUMPING

The action of the pharyngeal muscles, which draws food through the pharynx of the worm.

NOSE-TOUCH RESPONSE

When forward-moving worms bump into an object with their nose, they reverse their direction of movement and back away.

DAUER LARVA

An example of facultative diapause. In conditions of low food availability and crowding, C. elegans larval development can follow an alternative pathway and form a third-stage larva that is specialized for dispersal and long-term survival. The presence of sufficient food ends diapause and normal development resumes.

HABITUATION

A decrease in response as a result of repeated stimulation that cannot be explained by sensory adaptation or fatigue.

PLASTICITY

The ability of a behaviour to change as a result of activity or experience.

IDENTIFIED NEURON

A recognizable neuron that occurs in the same location and has the same function in every member of a species.

GRINDER

Muscle cells in the terminal bulb of the pharynx secrete thick, ridged cuticles that work together to grind up bacteria and pass it to the intestine.

ACTION POTENTIAL

The localized reversal and then restoration of electrical potential between the inside and the outside of a neuron or muscle cell

MECHANOSENSORY NEURON

A sensory neuron that is specialized to detect mechanical stimulation (that is, touch or vibration).

INTERNEURON

A neuron that connects with and transmits information only to local neurons.

INHIBITORY POTENTIAL

A hyperpolarization that results from inhibitory synaptic input.

HYPERPOLARIZATION

Refers to any change of the membrane potential to a value that is more negative than the resting potential.

GATED

Ion channels, such as potassium or calcium channels, can be opened by either a neurotransmitter (for example, glutamate gated or cyclic-nucleotide gated) or by changes in the electrical potential of the neuron (that is, voltage gated).

CALCIUM TRANSIENT

A brief change in fluorescence intensity induced by calcium entering the cell through a voltage-gated calcium channel.

DENDRITIC PROCESS

A branched, tree-like process that is attached to the cell body of a neuron and that receives input from the axons of other neurons.

NERVE RING

In Caenorhabditis elegans, many of the neurons in the nervous system surround the pharynx. Processes from these neurons form an external ring around the pharynx.

OSMOTIC AVOIDANCE

Movement away from high concentrations of sugars and salts.

PATCH CLAMP

A technique for recording changes in electrical potentials of individual neurons. It is used as a way of recording neuronal activity.

DISHABITUATION

The rapid facilitation of a behavioural response (often by a new or noxious stimulus) that has been habituated back towards the initial response levels.

SENSITIZATION

An alteration of a baseline-level behavioural response (often by a noxious or arousing stimulus) to levels that are significantly above baseline.

CONTEXT CONDITIONING

Some aspect in the environment (the context) becomes associated with a stimulus and influences later behaviour. (For example, worms habituated to the presence of a distinctive odour showed greater retention of habituation in the presence of the odour than in the absence of the odour.)

AMPHIDS

In nematodes, the chemosensory organs that are located laterally in pairs, in the anterior of the body.

DELAYED RECTIFIER

A channel that opens when a membrane is depolarized; the membrane repolarizes after an action potential.

CHOLINERGIC NEURON

A neuron that uses acetylcholine as its neurotransmitter.

RNA INTERFERENCE

(RNAi). A process by which double-stranded RNA silences specifically the expression of homologous genes through degradation of their cognate mRNA.

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Rankin, C. From gene to identified neuron to behaviour in Caenorhabditis elegans. Nat Rev Genet 3, 622–630 (2002). https://doi.org/10.1038/nrg864

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