(An in-progress 3D reconstruction of the C. elegans connectome. Dots represent the cell bodies of neurons; long lines represent the neurons' axons and dendrites. Credit: The OpenWorm Project, image generated by neuroConstruct)
As soon as Brenner and his colleagues at the University of Cambridge completed the 1986 draft of the C. elegans connectome, a few things became clear. First, scientists were able to label every one of the 302 neurons as either a sensory neuron (one that collects information from the environment, such as temperature or pressure); a motor neuron that controls muscles; or an interneuron, which connects the two. Scientists had already identified some neurons as motor or sensory by destroying them with lasers and observing what abilities the worm lost or retained. With the connectome, they could categorize all of C. elegans's neurons by referencing the number and types of connections between them. On average, sensory neurons make more presynaptic connections (sites where neurons spit out chemical messages) and fewer postsynaptic connections (where neurons receive chemical messages) because sensory neurons are mainly in the business of sending information to other cells. Motor neurons show the inverse trend. Each type of neuron constituted about one third of the C. elegans nervous system. The wiring diagram also allowed scientists to immediately identify how a neuron of interest was linked to other neurons. If a researcher zapped a neuron near the worm's head and discovered that the nematode no longer inched toward food, he could look up that neuron in the connectome and see exactly how it was connected to motor neurons.
In the 1980s, as a postdoctoral student in Brenner's lab, Martin Chalfie—now at Columbia University—used the C. elegans wiring diagram to explain one of the worm's behaviors: He identified the specific neural circuits responsible for the worm's tendency to wriggle backward when poked on the head and to squirm forward when touched on the tail. "The connectome was absolutely critical," Chalfie says. "Without it, we simply would not have known which cells were connected to which." By combining the wiring diagram with evidence from previous research, Chalfie predicted that a particular set of interneurons mediated forward movement and that another was involved in backward movement. Annihilating those neurons with lasers confirmed his predictions.
In the following 25 years researchers have continued to use the C. elegans connectome to study the worm's nervous system and behavior. In combination with genetic analysis and tools that eavesdrop on electrical activity within the worm's neurons, the connectome has helped researchers understand how C. elegans responds to temperature, chemicals and mechanical stimulation as well as how the worms mate and lay eggs. Scientists have also used the connectome to discover talents no one knew the nematode possessed: X. Z. Shawn Xu of the University of Michigan identified four neurons in the worm's body that respond to light—a surprising ability for a creature that lives between grains of soil in complete darkness. "Nearly every C. elegans neuroscience study (as long as it involves behavior) benefited from this connectome," Xu wrote in an e-mail message.