Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex

TLDR

Microglia are resident immune cells of the brain that increasingly are recognized as key mediators of normal neurophysiology, especially during early development, where monocular deprivation during the visual critical period induces structural and functional changes in cortical binocular connections. The study aims to demonstrate that microglia are essential for ocular dominance plasticity. To investigate this, the authors focused on the P2Y12 purinergic receptor, selectively expressed in non‑activated microglia and mediating process motility, and disrupted it to assess its role in monocular deprivation‑induced plasticity. Microglia respond to monocular deprivation by altering morphology, motility, phagocytic behavior, and synaptic interactions, and disrupting P2Y12 abolishes this response and ocular dominance plasticity, showing that microglia actively mediate experience‑dependent plasticity in the adolescent visual cortex.

Abstract

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.