Microglial Gi-dependent dynamics regulate brain network hyperexcitability

Microglial surveillance is a key feature of brain physiology and disease. Here, we found that G i -dependent microglial dynamics prevent neuronal network hyperexcitability. By generating Mg PTX mice to genetically inhibit G i 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, G i -dependent microglia dynamics may prevent hyperexcitability in neurological diseases. Merlini, Rafalski et al. show that dynamic microglial brain surveillance prevents hyperexcitability and seizures by G i -dependent microglia–neuron interactions in response to evoked neuronal activity to maintain physiological network synchronization.