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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8500094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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