Synaptic plasticity and synaptic reorganization regulated by microglia

Microglia are generally believed to be brain macrophages, which become phagocytic cells after cellular activation in response to inflammation or injury in the brain. However, accumulating evidence suggests that microglia modulate neurotransmission and synaptic plasticity by secretion of several soluble factors. Importantly, microglia secret glycine to enhance NMDA receptor-mediated responses and hippocampal long-term potentiation, a cellular basis of learning and memory. Although the expression of NMDA receptors was also observed in microglia, NMDA receptor-mediated responses were not induced in microglia. This suggests that NMDA receptors expressed in microglia are not functional. Besides the modulation of synaptic transmission, microglia also play an important role in synaptic remodeling by the pruning of unnecessary synapses and axon terminals during the postnatal developmental stage and adaptation to novel environments even in the healthy brain. Furthermore, we have recently found that clock genes in microglia drive P2Y₁₂R and cathepsin S to regulate diurnal change in the synaptic activity. Therefore, defects in these microglial functions may eventually result in several brain diseases including neuropsychiatric disorders.