Abstract
Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, particularly during early development. Here we demonstrate that microglia are critical for ocular dominance plasticity. During the visual critical period, closure of one eye elicits changes in the structure and function of connections underlying binocular responses of neurons in the visual cortex. We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity. These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain.
Highlights
Microglia are the resident immune cells of the brain
To determine whether microglia contribute to circuit changes that occur during Ocular dominance plasticity (ODP), we first examined whether these cells showed alterations in their dynamic behaviour following monocular deprivation (MD) during the visual critical period (P21–P35 in mice25)
To assay microglial morphological responses to different phases of ODP, we examined microglia in fixed sections of binocular visual cortex contralateral to the deprived eye in control animals (n 1⁄4 4) and animals that were monocularly deprived for 12 h (n 1⁄4 3), 1 day (n 1⁄4 3), 2 days (n 1⁄4 4), 4 days (n 1⁄4 4) or 7 days (n 1⁄4 3; Fig. 1a)
Summary
Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, during early development. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain. Cells that were initially biased to respond to inputs from the closed eye responded more strongly to inputs from the open eye[6] Since this experiencedependent plasticity has served not just to inform and improve treatment of amblyopic children, and as a model to understand general mechanisms of activity-dependent plasticity that are applicable to other brain regions and sensory systems, both during development and throughout the lifespan. Given the welldocumented roles of purinergic signalling in neuron–astrocyte communication[24], we posited that P2Y12 may facilitate neuron– microglia crosstalk during ODP
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