Microglia regulate chandelier cell axo-axonic synaptogenesis

Gallo, Nicholas B, Berisha, Artan, Van Aelst, Linda (March 2022) Microglia regulate chandelier cell axo-axonic synaptogenesis. Proceedings of the National Academy of Sciences of USA, 119 (11). e2114476119. ISSN 0027-8424

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Abstract

SignificanceChandelier cells (ChCs) are a unique type of GABAergic interneuron that form axo-axonic synapses exclusively on the axon initial segment (AIS) of neocortical pyramidal neurons (PyNs), allowing them to exert powerful yet precise control over PyN firing and population output. The importance of proper ChC function is further underscored by the association of ChC connectivity defects with various neurological conditions. Despite this, the cellular mechanisms governing ChC axo-axonic synapse formation remain poorly understood. Here, we identify microglia as key regulators of ChC axonal morphogenesis and AIS synaptogenesis, and show that disease-induced aberrant microglial activation perturbs proper ChC synaptic development/connectivity in the neocortex. In doing so, such findings highlight the therapeutic potential of manipulating microglia to ensure proper brain wiring.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > small molecules > GABA bioinformatics > genomics and proteomics organism description > animal organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse > axo-axonic synapse organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organism description > animal > mammal organs, tissues, organelles, cell types and functions > cell types and functions > cell types > microglia organs, tissues, organelles, cell types and functions > cell types and functions > cell types > microglia organs, tissues, organelles, cell types and functions > cell types and functions > cell types > microglia organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent bioinformatics > genomics and proteomics > small molecules organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse organs, tissues, organelles, cell types and functions > tissues types and functions > synaptogenesis
CSHL Authors:	Gallo, Nicholas Van Aelst, Linda Berisha, Artan
Communities:	CSHL labs > Van Aelst lab CSHL Cancer Center Program CSHL Cancer Center Program > Cellular Communication in Cancer Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 March 2022
Date Deposited:	17 Mar 2022 13:07
Last Modified:	09 Feb 2024 18:45
PMCID:	PMC8931231
URI:	https://repository.cshl.edu/id/eprint/40552

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