Homophilic wiring principles underpin neuronal network topology in vitro

Paper: bioRxiv paper Code: GitHub AbstractEconomical efficiency has been a popular explanation for how networks organize themselves within the developing nervous system. However, the precise nature of the economic negotiations governing this self-organization is unclear. We approach this problem by combining high-density microelectrode array (HD-MEA) recordings, which allow detailed characterization of the ongoing extracellular electrical activity of individual neurons in vitro, with a generative modeling approach capable of simulating network formation. The best fitting model uses a homophilic generative principle in which neurons form connections to other neurons with similar connectivity patterns to themselves. This homophily-based mechanism for neuronal network emergence accounts for a wide range of observations that are described, but not sufficiently explained, by traditional analyses of network topology. Using rodent and human mono-layer and organoid cultures, we show that homophilic generative mechanisms account for the topology of emerging cellular functional connectivity, representing an important wiring principle and determining factor of neuronal network formation in vitro.