Resting microglia respond to and regulate neuronal activity in vivo

Microglia are the primary immune cells in the brain. Under pathological conditions, they become activated and participate in scavenging, inflammation and tissue repair in response to brain injury. While the function and underlying mechanism of activated microglia have been intensively studied in the past decades, physiological functions of resting microglia remain largely underestimated. In our recent work, by simultaneously monitoring both the motility of resting microglial processes and the activity of surrounding neurons in intact zebrafish optic tectum, we examined the interaction between resting microglia and neurons. Local increase in neuronal activity attracts resting microglial processes and drives them to contact neurons with high levels of activity. This process is mediated by neuronal release of “find-me” signals such as ATP via pannexin-1 hemichannels and requires small Rho GTPase Rac in microglia. Reciprocally, the microglia-neuron contact reduces both the spontaneous and visually evoked activities of contacted neurons. We here summarize and explain the key results in the context of our previous work.