Neuronal contact predicts connectivity in the C. elegans brain

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 Sperrys chemoaffinity model1, a neuron selectively chooses a synaptic partner among several different, adjacent target cells, based on a specific molecular recognition code2. 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 connectivity3,4. However, whether Peters rule plays an important role in synaptic wiring remains unresolved5. 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.