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Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice
NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387434/ https://www.ncbi.nlm.nih.gov/pubmed/34433814 http://dx.doi.org/10.1038/s41467-021-25356-2 |
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author | Lee, Eunee Lee, Seungjoon Shin, Jae Jin Choi, Woochul Chung, Changuk Lee, Suho Kim, Jihye Ha, Seungmin Kim, Ryunhee Yoo, Taesun Yoo, Ye-Eun Kim, Jisoo Noh, Young Woo Rhim, Issac Lee, Soo Yeon Kim, Woohyun Lee, Taekyung Shin, Hyogeun Cho, Il-Joo Deisseroth, Karl Kim, Sang Jeong Park, Joo Min Jung, Min Whan Paik, Se-Bum Kim, Eunjoon |
author_facet | Lee, Eunee Lee, Seungjoon Shin, Jae Jin Choi, Woochul Chung, Changuk Lee, Suho Kim, Jihye Ha, Seungmin Kim, Ryunhee Yoo, Taesun Yoo, Ye-Eun Kim, Jisoo Noh, Young Woo Rhim, Issac Lee, Soo Yeon Kim, Woohyun Lee, Taekyung Shin, Hyogeun Cho, Il-Joo Deisseroth, Karl Kim, Sang Jeong Park, Joo Min Jung, Min Whan Paik, Se-Bum Kim, Eunjoon |
author_sort | Lee, Eunee |
collection | PubMed |
description | NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2(–/–) mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2(–/–) Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2(–/–) Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2(–/–) mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition. |
format | Online Article Text |
id | pubmed-8387434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83874342021-09-22 Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice Lee, Eunee Lee, Seungjoon Shin, Jae Jin Choi, Woochul Chung, Changuk Lee, Suho Kim, Jihye Ha, Seungmin Kim, Ryunhee Yoo, Taesun Yoo, Ye-Eun Kim, Jisoo Noh, Young Woo Rhim, Issac Lee, Soo Yeon Kim, Woohyun Lee, Taekyung Shin, Hyogeun Cho, Il-Joo Deisseroth, Karl Kim, Sang Jeong Park, Joo Min Jung, Min Whan Paik, Se-Bum Kim, Eunjoon Nat Commun Article NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2(–/–) mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2(–/–) Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2(–/–) Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2(–/–) mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition. Nature Publishing Group UK 2021-08-25 /pmc/articles/PMC8387434/ /pubmed/34433814 http://dx.doi.org/10.1038/s41467-021-25356-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lee, Eunee Lee, Seungjoon Shin, Jae Jin Choi, Woochul Chung, Changuk Lee, Suho Kim, Jihye Ha, Seungmin Kim, Ryunhee Yoo, Taesun Yoo, Ye-Eun Kim, Jisoo Noh, Young Woo Rhim, Issac Lee, Soo Yeon Kim, Woohyun Lee, Taekyung Shin, Hyogeun Cho, Il-Joo Deisseroth, Karl Kim, Sang Jeong Park, Joo Min Jung, Min Whan Paik, Se-Bum Kim, Eunjoon Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
title | Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
title_full | Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
title_fullStr | Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
title_full_unstemmed | Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
title_short | Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
title_sort | excitatory synapses and gap junctions cooperate to improve pv neuronal burst firing and cortical social cognition in shank2-mutant mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387434/ https://www.ncbi.nlm.nih.gov/pubmed/34433814 http://dx.doi.org/10.1038/s41467-021-25356-2 |
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