Spatial continuity of neurons explains non-random network architecture

Summary Neuronal networks are characterized by complex and functionally relevant connectivity motifs. We developed an intuitive explanation for its emergence. While a class of neurons on average innervates its entire surroundings, each individual neuron can only cover a small part of the space. That region is different for each neuron but not completely random, as it is physically constrained by the spatial continuity of the axon. This hypothesis was successfully tested against a morphologically detailed model and an electron-microscopic reconstruction of cortical connectivity. We distilled it into a stochastic algorithm that generates networks, which accurately match the reference data. Our work bridges previous efforts to capture network complexity with top-down or bottom-up methods, that is, by adding complexity constraints to simple stochastic models or by predicting synapses from neuron appositions. It may improve the understanding of the impact of neuron malformations and the functional role of non-random network structure in simplified models.