Long-Range Ca2+ Waves Transmit Brain-Damage Signals to Microglia

Summary Microglia are the resident phagocytes of the brain that are responsible for the clearance of injured neurons, an essential step in subsequent tissue regeneration. How death signals are controlled both in space and time to attract these cells toward the site of injury is a topic of great interest. To this aim, we have used the optically transparent zebrafish larval brain and identified rapidly propagating Ca 2+ waves that determine the range of microglial responses to neuronal cell death. We show that while Ca 2+ -mediated microglial responses require ATP, the spreading of intercellular Ca 2+ waves is ATP independent. Finally, we identify glutamate as a potent inducer of Ca 2+ -transmitted microglial attraction. Thus, this real-time analysis reveals the existence of a mechanism controlling microglial targeted migration to neuronal injuries that is initiated by glutamate and proceeds across the brain in the form of a Ca 2+ wave. Video Abstract