Mind-Mapping

The connectome of the humble roundworm, Caenorhabditis elegans, is revealing intriguing clues about how neural networks analyze and act on information.

C. elegans, apparently dancing at a rave.

The C. elegans connectome was officially mapped back in 1986. It contains only 302 neurons and about 8,000 synapses – compared to one hundred billion neurons and some seven hundred trillion synaptic connections in a human connectome. Even so, it’s only recently that a team led by Dr. Cornelia I. Bargmann at the Howard Hughes Medical Institute have made serious progress in understanding how this worm connectome (click that link; it’s awesome) represents data, passes it around, analyzes it, and converts its conclusions into action.

This research should provide a simplified framework for understanding this worm’s neural activity – and ultimately, the human connectome.

Though brains throughout the animal kingdom display a wide variety of anatomical organization, they’re all organized on the basis of nodal functional networks, in which certain areas act as processing hubs, which in turn feed their output to more central hubs. Here’s one example:

It turns out that [C. elegans] social behavior in the worm is controlled by a pair of neurons called RMG. The two RMG neurons receive input from various sensory neurons that detect the several environmental cues that make worms aggregate. RMG integrates this information and sends signals to the worm’s muscles. The usual role of the RMG neurons is to promote social behavior, but when the npr-1 gene is active, the RMG neurons cannot receive input from their sensory neurons, and the worms switch to solitary behavior.

This RMG circuit is obviously nowhere near as complex as the inner debate that goes on in human minds throughout an average day. Still, it’s fascinating to see how close we are to understanding some of the basic neural mechanisms that motivate action selection.

Even so, all these neuronal connections are just the beginning of the complexity Dr. Bargmann’s team is discovering. In addition to the connectome’s synaptic wiring – which uses chemical signals to mediate neurotransmission – the worm’s nervous system also incorporates gap junctions, which allow chemicals to pass directly between neurons through tiny pores. And the system only gets more complex from there:

Not only does the worm’s connectome … have two separate wiring diagrams superimposed on each other, but there is a third system that keeps rewiring the wiring diagrams. This is based on neuropeptides, hormonelike chemicals that are released by neurons to affect other neurons. The neuropeptides probably help control the brain’s general status, or mood.

The worm’s behavior cannot be computed from the wiring diagram [alone]: the pattern of connections is changing all the time under the influence of the worm’s 250 neuropeptides. The connectome shows the electrical connections, and hence the quickest paths for information to move through the worm’s brain. “But if only a subset of neurons are available at any time, the connectome is ambiguous,” [Bargmann] says.

So between synaptic connections, gap-junction connections, and overall neuronal availability mediated by neuropeptides, the functionality of the worm connectome looks to be as complex as we might expect from such a dense organic machine…or perhaps even more than anyone could’ve predicted.

The field of connectomics is undergoing explosive growth right now, but connectomic neuroscientists are still coming to grips with the true scale of the tasks before them. Like the first sailing voyages across the Atlantic, this journey promises to be as vast as it is rewarding.

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