Pío del Río Hortega, the father of the study of microglia, referred to microglia with highly branched fine processes in the healthy brain as "resting microglia," because he thought these cells were quiescent. After brain injury, these resting microglia change their morphology into an activated type, which have phagocytic activity at the sites of neuronal damage and inflammation. At present, approximately 90 years after the discovery of microglia, microglia in the healthy brains of live animals are found to be very active using a two-photon scanning laser microscope, and are much more active than any other cells in the brain. Beyond their role as brain-resident macrophages, many lines of evidence have shown that microglia have essential roles in the maturation and maintenance of neuronal circuits in the developing and adult brain through both the elimination and formation of dendritic spines through their processes. Furthermore, the length and structural complexity of highly branched fine processes are regulated by the microglial intrinsic circadian clock. Dysfunction of the dendritic spines and disturbances of the circadian clock system are widely accepted characteristic abnormalities in neuropsychiatric disorders, including autism. Therefore, the growing understanding of the movement and functions of microglial processes might aid in the development of novel pharmacological interventions against neuropsychiatric disorders, which are associated with synapse loss and aberrant neuronal connectivity.
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