Abstract
Microglia, the resident immune cells of the brain, have emerged as crucial regulators of synaptic refinement and brain wiring. However, whether the remodeling of distinct synapses during development is mediated by specialized microglia is unknown. Here, using in vivo two-photon imaging, we show that GABA-receptive microglia selectively interact with inhibitory cortical synapses during a critical window of mouse postnatal development. GABA initiates a transcriptional synapse remodeling program within these specialized microglia, which in turn sculpt inhibitory connectivity without impacting excitatory synapses. Ablation of GABAB receptors within microglia impairs this process and leads to stereotyped repetitive behavior and hyperactivity. These findings demonstrate that GABA-receptive microglia differentially engage with specific synapse types during development.
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