Microglia: Activity-dependent regulators of neural circuits

It has been more than a century since Pío del Río-Hortega first characterized microglia in histological stains of brain tissue. Since then, significant advances have been made in understanding the role of these resident central nervous system (CNS) macrophages. In particular, it is now known that microglia can sense neural activity and modulate neuronal circuits accordingly. We review the mechanisms by which microglia detect changes in neural activity to then modulate synapse numbers in the developing and mature CNS. This includes responses to both spontaneous and experience-driven neural activity. We further discuss activity-dependent mechanisms by which microglia regulate synaptic function and neural circuit excitability. Together, our discussion provides a comprehensive review of the activity-dependent functions of microglia within neural circuits in the healthy CNS, and highlights exciting new open questions related to understanding more fully microglia as key components and regulators of neural circuits.