Microglial Gi-dependent dynamics regulate brain network hyperexcitability

Microglial surveillance is a key feature of brain physiology and disease. Here, we found that Gi-dependent microglial dynamics prevent neuronal network hyperexcitability. By generating MgPTX mice to genetically inhibit Gi in microglia, we show that sustained reduction of microglia brain surveillance and directed process motility induced spontaneous seizures and increased hypersynchrony after physiologically evoked neuronal activity in awake adult mice. Thus, Gi-dependent microglia dynamics may prevent hyperexcitability in neurological diseases. Merlini, Rafalski et al. show that dynamic microglial brain surveillance prevents hyperexcitability and seizures by Gi-dependent microglia–neuron interactions in response to evoked neuronal activity to maintain physiological network synchronization.