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GABA-receptive microglia selectively sculpt developing inhibitory circuits.
Favuzzi, Emilia; Huang, Shuhan; Saldi, Giuseppe A; Binan, Loïc; Ibrahim, Leena A; Fernández-Otero, Marian; Cao, Yuqing; Zeine, Ayman; Sefah, Adwoa; Zheng, Karen; Xu, Qing; Khlestova, Elizaveta; Farhi, Samouil L; Bonneau, Richard; Datta, Sandeep Robert; Stevens, Beth; Fishell, Gord.
Affiliation
  • Favuzzi E; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Huang S; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Saldi GA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biology, New York University, New York, NY 10003, USA.
  • Binan L; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Ibrahim LA; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Fernández-Otero M; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Cao Y; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Zeine A; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Sefah A; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Zheng K; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Xu Q; New York University Abu Dhabi, Abu Dhabi, UAE.
  • Khlestova E; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Farhi SL; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Bonneau R; Department of Biology, New York University, New York, NY 10003, USA; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA; Center for Data Science, New York University, New York, NY 10011, USA.
  • Datta SR; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Stevens B; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA 02115, USA.
  • Fishell G; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: gordon_fishell@hms.harvard.edu.
Cell ; 184(15): 4048-4063.e32, 2021 07 22.
Article in En | MEDLINE | ID: mdl-34233165
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.
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Full text: 1 Database: MEDLINE Main subject: Microglia / Gamma-Aminobutyric Acid / Neural Inhibition Limits: Animals / Humans Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Microglia / Gamma-Aminobutyric Acid / Neural Inhibition Limits: Animals / Humans Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States