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NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain

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 understoo...

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Autores principales: Mahadevan, Vivek, Mitra, Apratim, Zhang, Yajun, Yuan, Xiaoqing, Peltekian, Areg, Chittajallu, Ramesh, Esnault, Caroline, Maric, Dragan, Rhodes, Christopher, Pelkey, Kenneth A., Dale, Ryan, Petros, Timothy J., McBain, Chris J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500094/
https://www.ncbi.nlm.nih.gov/pubmed/34630033
http://dx.doi.org/10.3389/fnmol.2021.712609
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author Mahadevan, Vivek
Mitra, Apratim
Zhang, Yajun
Yuan, Xiaoqing
Peltekian, Areg
Chittajallu, Ramesh
Esnault, Caroline
Maric, Dragan
Rhodes, Christopher
Pelkey, Kenneth A.
Dale, Ryan
Petros, Timothy J.
McBain, Chris J.
author_facet Mahadevan, Vivek
Mitra, Apratim
Zhang, Yajun
Yuan, Xiaoqing
Peltekian, Areg
Chittajallu, Ramesh
Esnault, Caroline
Maric, Dragan
Rhodes, Christopher
Pelkey, Kenneth A.
Dale, Ryan
Petros, Timothy J.
McBain, Chris J.
author_sort Mahadevan, Vivek
collection PubMed
description 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.
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spelling pubmed-85000942021-10-09 NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain Mahadevan, Vivek Mitra, Apratim Zhang, Yajun Yuan, Xiaoqing Peltekian, Areg Chittajallu, Ramesh Esnault, Caroline Maric, Dragan Rhodes, Christopher Pelkey, Kenneth A. Dale, Ryan Petros, Timothy J. McBain, Chris J. Front Mol Neurosci Neuroscience 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. Frontiers Media S.A. 2021-09-14 /pmc/articles/PMC8500094/ /pubmed/34630033 http://dx.doi.org/10.3389/fnmol.2021.712609 Text en Copyright © 2021 Mahadevan, Mitra, Zhang, Yuan, Peltekian, Chittajallu, Esnault, Maric, Rhodes, Pelkey, Dale, Petros and McBain. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Mahadevan, Vivek
Mitra, Apratim
Zhang, Yajun
Yuan, Xiaoqing
Peltekian, Areg
Chittajallu, Ramesh
Esnault, Caroline
Maric, Dragan
Rhodes, Christopher
Pelkey, Kenneth A.
Dale, Ryan
Petros, Timothy J.
McBain, Chris J.
NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain
title NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain
title_full NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain
title_fullStr NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain
title_full_unstemmed NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain
title_short NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain
title_sort nmdars drive the expression of neuropsychiatric disorder risk genes within gabaergic interneuron subtypes in the juvenile brain
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500094/
https://www.ncbi.nlm.nih.gov/pubmed/34630033
http://dx.doi.org/10.3389/fnmol.2021.712609
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