Maps of the connections between neurons are being assembled for several organisms, including humans. But connectivity alone is insufficient for understanding the mechanisms of behavior. Nowhere is this more obvious than in the nematode C. elegans, where the nearly complete connectome has been available for over 25 years yet little is known about the neural basis of most of its behavior. Here we combine known neuroanatomical constraints from the C. elegans connectome with a simplified body and environment, and use optimization techniques to fill in the missing electrophysiological parameters in plausible ways so as to produce worm-like behavior. We focus on one spatial orientation behavior, where the reactions to sensory input depend on the worm's internal state at the time of the stimulus: salt klinotaxis. By exploring the possibilities for what is unknown in ways that are consistent with what is known, we generate an ensemble of hypotheses about the neural basis of this behavior. Studying the structure of this ensemble, we formulate new experiments that can distinguish between the various hypotheses. This methodology is likely to accelerate the discovery and understanding of the biological circuitry underlying the behavior of interest, before a complete electrophysiological characterization is available.
Izquierdo EJ, Beer RD (2013) Connecting a Connectome to Behavior: An Ensemble of Neuroanatomical Models of C. elegans Klinotaxis. PLoS Comput Biol 9(2): e1002890. http://dx.doi.org/10.1371/journal.pcbi.1002890