Bridging the gap between the connectome and whole-brain activity in C. elegans

A fundamental goal of neuroscience is to understand how anatomy determines the functional properties of the nervous system. However, previous work has failed to show how the functional connections between neurons are derived from the connectome in the nematode C. elegans, raising questions about the extent to which anatomy is informative of signaling^1-3. Here, we address this problem using a connectome-constrained dynamical model of the brain, which we fit to whole-brain recordings of neural activity during optogenetic perturbation of single neurons². This dynamical model, which contains non-zero weights only between anatomically connected neurons, captured causal interactions between all pairs of neurons 92% as well as the reproducibility of the perturbation data themselves. This included interactions between anatomically unconnected neurons, which the model accounted for in terms of signal propagation over paths that include multiple neurons. Strikingly, alternative models fit using a shuffled connectome achieved much lower performance. Finally, we found that adding connections beyond those in the connectome did not improve the model's ability to capture causal interactions. Our dynamical model thus provides the strongest link yet between the connectivity of the C. elegans nervous system and its causal interactions and provides a blueprint for exploring the link between structure and function in other organisms.