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The effect of alterations of schizophrenia-associated genes on gamma band oscillations

Abnormalities in the synchronized oscillatory activity of neurons in general and, specifically in the gamma band, might play a crucial role in the pathophysiology of schizophrenia. While these changes in oscillatory activity have traditionally been linked to alterations at the synaptic level, we dem...

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Autores principales: Metzner, Christoph, Mäki-Marttunen, Tuomo, Karni, Gili, McMahon-Cole, Hana, Steuber, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261091/
https://www.ncbi.nlm.nih.gov/pubmed/35854005
http://dx.doi.org/10.1038/s41537-022-00255-7
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author Metzner, Christoph
Mäki-Marttunen, Tuomo
Karni, Gili
McMahon-Cole, Hana
Steuber, Volker
author_facet Metzner, Christoph
Mäki-Marttunen, Tuomo
Karni, Gili
McMahon-Cole, Hana
Steuber, Volker
author_sort Metzner, Christoph
collection PubMed
description Abnormalities in the synchronized oscillatory activity of neurons in general and, specifically in the gamma band, might play a crucial role in the pathophysiology of schizophrenia. While these changes in oscillatory activity have traditionally been linked to alterations at the synaptic level, we demonstrate here, using computational modeling, that common genetic variants of ion channels can contribute strongly to this effect. Our model of primary auditory cortex highlights multiple schizophrenia-associated genetic variants that reduce gamma power in an auditory steady-state response task. Furthermore, we show that combinations of several of these schizophrenia-associated variants can produce similar effects as the more traditionally considered synaptic changes. Overall, our study provides a mechanistic link between schizophrenia-associated common genetic variants, as identified by genome-wide association studies, and one of the most robust neurophysiological endophenotypes of schizophrenia.
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spelling pubmed-92610912022-07-13 The effect of alterations of schizophrenia-associated genes on gamma band oscillations Metzner, Christoph Mäki-Marttunen, Tuomo Karni, Gili McMahon-Cole, Hana Steuber, Volker Schizophrenia (Heidelb) Article Abnormalities in the synchronized oscillatory activity of neurons in general and, specifically in the gamma band, might play a crucial role in the pathophysiology of schizophrenia. While these changes in oscillatory activity have traditionally been linked to alterations at the synaptic level, we demonstrate here, using computational modeling, that common genetic variants of ion channels can contribute strongly to this effect. Our model of primary auditory cortex highlights multiple schizophrenia-associated genetic variants that reduce gamma power in an auditory steady-state response task. Furthermore, we show that combinations of several of these schizophrenia-associated variants can produce similar effects as the more traditionally considered synaptic changes. Overall, our study provides a mechanistic link between schizophrenia-associated common genetic variants, as identified by genome-wide association studies, and one of the most robust neurophysiological endophenotypes of schizophrenia. Nature Publishing Group UK 2022-04-28 /pmc/articles/PMC9261091/ /pubmed/35854005 http://dx.doi.org/10.1038/s41537-022-00255-7 Text en © The Author(s) 2022 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
Metzner, Christoph
Mäki-Marttunen, Tuomo
Karni, Gili
McMahon-Cole, Hana
Steuber, Volker
The effect of alterations of schizophrenia-associated genes on gamma band oscillations
title The effect of alterations of schizophrenia-associated genes on gamma band oscillations
title_full The effect of alterations of schizophrenia-associated genes on gamma band oscillations
title_fullStr The effect of alterations of schizophrenia-associated genes on gamma band oscillations
title_full_unstemmed The effect of alterations of schizophrenia-associated genes on gamma band oscillations
title_short The effect of alterations of schizophrenia-associated genes on gamma band oscillations
title_sort effect of alterations of schizophrenia-associated genes on gamma band oscillations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261091/
https://www.ncbi.nlm.nih.gov/pubmed/35854005
http://dx.doi.org/10.1038/s41537-022-00255-7
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