GABA-receptive microglia selectively sculpt developing inhibitory circuits

Emilia Favuzzi, Shuhan Huang, Giuseppe A. Saldi, Loïc Binan, Leena A. Ibrahim, Marian Fernández-Otero, Yuqing Cao, Ayman Zeine, Adwoa Sefah, Karen Zheng, Qing Xu, Elizaveta Khlestova, Samouil L. Farhi, Richard Bonneau, Sandeep Robert Datta, Beth Stevens, Gord Fishell

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)4048-4063.e32
JournalCell
Volume184
Issue number15
DOIs
StatePublished - Jul 22 2021

Keywords

  • cerebral cortex
  • development
  • glia-neuron interactions
  • inhibitory synapses
  • interneurons
  • microglia
  • neurodevelopmental disorders

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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