GABA-receptive microglia selectively sculpt developing inhibitory circuits

Cell. 2021 Jul 22;184(15):4048-4063.e32. doi: 10.1016/j.cell.2021.06.018. Epub 2021 Jul 6.


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.

Keywords: cerebral cortex; development; glia-neuron interactions; inhibitory synapses; interneurons; microglia; neurodevelopmental disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice
  • Microglia / metabolism*
  • Neural Inhibition / physiology*
  • Parvalbumins / metabolism
  • Phenotype
  • Receptors, GABA-B / metabolism
  • Synapses / physiology
  • Transcription, Genetic
  • gamma-Aminobutyric Acid / metabolism*


  • Parvalbumins
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid