Structure, function and dynamics of the C. elegans nervous system*

The nematode C. elegans’ small nervous system of 302 neurons and its completely mapped anatomical wiring, or connectome, make it a powerful model for exploring biological neural networks. Yet even with this granular anatomical description, it remains challenging to accurately predict brain wide neural dynamics or detailed circuit function because it is unknown for many neural connections how signals propagate from one neuron to the next. To fill this gap, we created a comprehensive neural response map of the C. elegans head at cellular resolution by measuring network calcium activity in response to single-neuron optogenetic perturbations for more than 10,000 neuron-pairs. We captured the sign (excitatory or inhibitory), strength, temporal properties, and the causal direction of signal propagation between neurons. We find that signal propagation in the brain differs from what anatomy predicts. Moreover, simulations constrained by our functional measurements better agree with spontaneous dynamics than do simulations constrained by anatomy. We find that extrasynaptic signaling, including via neuropeptides, is one mechanism underlying this divergence of structure and function.  Because neuropeptide machinery is widely expressed in many nervous systems, our findings may have broader implications for structure-function relations in other organisms.