GABA-receptive microglia selectively sculpt developing inhibitory circuits
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 synapse types during development is mediated by specialized microglia is unknown. Here, we show that GABA-receptive microglia sel...
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Published in | Cell Vol. 184; no. 15; pp. 4048 - 4063.e32 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
22.07.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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 synapse types during development is mediated by specialized microglia is unknown. Here, 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 behavioral abnormalities. These findings demonstrate that brain wiring relies on the selective communication between matched neuronal and glial cell types.
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•GABA-receptive microglia interact with inhibitory synapses during development•Removing GABABRs from microglia alters inhibitory but not excitatory connectivity•Synapse pruning genes are altered in GABA-receptive microglia lacking GABABRs•Mice lacking microglial GABAB1Rs exhibit behavioral abnormalities
GABA-receptive microglia selectively prune inhibitory synapses in development and disruption of this microglial response leads to behavioral abnormalities highlighting a critical function of selective communication between microglia and neuronal cell types. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceptualization, E.F.; Methodology, E.F., L.B., Q.X., and S.F.; Software, E.F., G.A.S., L.B., A.Z., and K.Z.; Formal Analysis, E.F., S.H., G.A.S., L.B., L.A.I., A.Z., A.S., and E.K.; Investigation, E.F., S.H., L.B., L.A.I., Y.C., and M.F.-O.; Resources, S.F., S.R.D., B.S., and G.F.; Data Curation, E.F. and G.A.S.; Writing - Original Draft, E.F. and G.F.; Writing - Review & Editing, all co-authors; Visualization, E.F. and G.A.S.; Supervision, R.B., S.R.D., B.S., and G.F.; Project Administration, E.F.; Funding Acquisition, E.F. and G.F. AUTHOR CONTRIBUTIONS |
ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/j.cell.2021.06.018 |