Neuronal contact predicts connectivity in theC. elegansbrain

Summary Axons must project to particular brain regions, contact adjacent neurons, and choose appropriate synaptic targets to form a nervous system. Multiple mechanisms have been proposed to explain synaptic partnership choice. In a ‘lock-and-key’ mechanism, first proposed by Sperry’s chemoaffinity model 1 , a neuron selectively chooses a synaptic partner among several different, adjacent target cells, based on a specific molecular recognition code 2 . Alternatively, Peters’ rule posits that neurons indiscriminately form connections with other neuron types in their proximity; hence, neighborhood choice, dictated by initial neuronal process outgrowth and position, is the sole predictor of connectivity 3,4 . However, whether Peters’ rule plays an important role in synaptic wiring remains unresolved 5 . To assess the nanoscale relationship between neuronal adjacency and connectivity, we evaluate the expansive set of C. elegans connectomes. We find that synaptic connectivity can be accurately modeled as a path-length-dependent process of neuronal adjacency and brain strata, offering strong support for Peters’ rule as an organizational principle of C. elegans brain wiring.