GABA-receptive microglia selectively sculpt developing inhibitory circuits

Microglia, the primary brain macrophages, regulate a plethora of processes that impact the organization of neural circuits, including synapse pruning. Whether microglia are generic effectors of synapse pruning or if specialized microglia are able to discriminate between distinct synapse types is unknown. We found that GABA-receptive microglia selectively interact with inhibitory cortical synapses during a critical window of mouse postnatal development. Single cell RNA-seq and MERFISH profiling showed that ablation of microglial GABAB receptors cell-autonomously alters a transcriptional synapse remodeling program. As a result, loss of GABABRs within microglia alters inhibitory connectivity without impacting excitatory synapses and leads to behavioral abnormalities. These findings demonstrate that distinct microglia differentially engage with specific synapse types during development.

 

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