In:
Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 14 ( 2021-9-14)
Abstract:
Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical, and physiological properties. However, the molecular mechanisms regulating their maturation remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates transcriptional regulation of gene expression in specific subtypes of MGE-derived interneurons, leading to altered subtype abundances. Notably, MGE-specific early developmental Grin1 loss results in a broad downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs in the juvenile brain. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.
Type of Medium:
Online Resource
ISSN:
1662-5099
DOI:
10.3389/fnmol.2021.712609
DOI:
10.3389/fnmol.2021.712609.s001
DOI:
10.3389/fnmol.2021.712609.s002
DOI:
10.3389/fnmol.2021.712609.s003
DOI:
10.3389/fnmol.2021.712609.s004
DOI:
10.3389/fnmol.2021.712609.s005
DOI:
10.3389/fnmol.2021.712609.s006
DOI:
10.3389/fnmol.2021.712609.s007
DOI:
10.3389/fnmol.2021.712609.s008
DOI:
10.3389/fnmol.2021.712609.s009
DOI:
10.3389/fnmol.2021.712609.s010
DOI:
10.3389/fnmol.2021.712609.s011
DOI:
10.3389/fnmol.2021.712609.s012
DOI:
10.3389/fnmol.2021.712609.s013
DOI:
10.3389/fnmol.2021.712609.s014
DOI:
10.3389/fnmol.2021.712609.s015
DOI:
10.3389/fnmol.2021.712609.s016
DOI:
10.3389/fnmol.2021.712609.s017
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2452967-9