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

doi:10.1016/j.cell.2021.06.018

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 journal › Article › peer-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 GABA_B 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 language	English (US)
Pages (from-to)	4048-4063.e32
Journal	Cell
Volume	184
Issue number	15
DOIs	https://doi.org/10.1016/j.cell.2021.06.018
State	Published - Jul 22 2021

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2021.06.018

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Favuzzi, E., Huang, S., Saldi, G. A., Binan, L., Ibrahim, L. A., Fernández-Otero, M., Cao, Y., Zeine, A., Sefah, A., Zheng, K., Xu, Q., Khlestova, E., Farhi, S. L., Bonneau, R., Datta, S. R., Stevens, B., & Fishell, G. (2021). GABA-receptive microglia selectively sculpt developing inhibitory circuits. Cell, 184(15), 4048-4063.e32. https://doi.org/10.1016/j.cell.2021.06.018

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title = "GABA-receptive microglia selectively sculpt developing inhibitory circuits",

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.",

keywords = "cerebral cortex, development, glia-neuron interactions, inhibitory synapses, interneurons, microglia, neurodevelopmental disorders",

author = "Emilia Favuzzi and Shuhan Huang and Saldi, {Giuseppe A.} and Lo{\"i}c Binan and Ibrahim, {Leena A.} and Marian Fern{\'a}ndez-Otero and Yuqing Cao and Ayman Zeine and Adwoa Sefah and Karen Zheng and Qing Xu and Elizaveta Khlestova and Farhi, {Samouil L.} and Richard Bonneau and Datta, {Sandeep Robert} and Beth Stevens and Gord Fishell",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jul,

day = "22",

doi = "10.1016/j.cell.2021.06.018",

language = "English (US)",

volume = "184",

pages = "4048--4063.e32",

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TY - JOUR

T1 - GABA-receptive microglia selectively sculpt developing inhibitory circuits

AU - Favuzzi, Emilia

AU - Huang, Shuhan

AU - Saldi, Giuseppe A.

AU - Binan, Loïc

AU - Ibrahim, Leena A.

AU - Fernández-Otero, Marian

AU - Cao, Yuqing

AU - Zeine, Ayman

AU - Sefah, Adwoa

AU - Zheng, Karen

AU - Xu, Qing

AU - Khlestova, Elizaveta

AU - Farhi, Samouil L.

AU - Bonneau, Richard

AU - Datta, Sandeep Robert

AU - Stevens, Beth

AU - Fishell, Gord

PY - 2021/7/22

Y1 - 2021/7/22

N2 - 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.

AB - 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.

KW - cerebral cortex

KW - development

KW - glia-neuron interactions

KW - inhibitory synapses

KW - interneurons

KW - microglia

KW - neurodevelopmental disorders

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U2 - 10.1016/j.cell.2021.06.018

DO - 10.1016/j.cell.2021.06.018

M3 - Article

C2 - 34233165

AN - SCOPUS:85110603073

SN - 0092-8674

VL - 184

SP - 4048-4063.e32

JO - Cell

JF - Cell

IS - 15

ER -

GABA-receptive microglia selectively sculpt developing inhibitory circuits

Abstract

Keywords

ASJC Scopus subject areas

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