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Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations

Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms...

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Autores principales: Mäki-Marttunen, Tuomo, Krull, Florian, Bettella, Francesco, Hagen, Espen, Næss, Solveig, Ness, Torbjørn V, Moberget, Torgeir, Elvsåshagen, Torbjørn, Metzner, Christoph, Devor, Anna, Edwards, Andrew G, Fyhn, Marianne, Djurovic, Srdjan, Dale, Anders M, Andreassen, Ole A, Einevoll, Gaute T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319172/
https://www.ncbi.nlm.nih.gov/pubmed/30475994
http://dx.doi.org/10.1093/cercor/bhy291
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author Mäki-Marttunen, Tuomo
Krull, Florian
Bettella, Francesco
Hagen, Espen
Næss, Solveig
Ness, Torbjørn V
Moberget, Torgeir
Elvsåshagen, Torbjørn
Metzner, Christoph
Devor, Anna
Edwards, Andrew G
Fyhn, Marianne
Djurovic, Srdjan
Dale, Anders M
Andreassen, Ole A
Einevoll, Gaute T
author_facet Mäki-Marttunen, Tuomo
Krull, Florian
Bettella, Francesco
Hagen, Espen
Næss, Solveig
Ness, Torbjørn V
Moberget, Torgeir
Elvsåshagen, Torbjørn
Metzner, Christoph
Devor, Anna
Edwards, Andrew G
Fyhn, Marianne
Djurovic, Srdjan
Dale, Anders M
Andreassen, Ole A
Einevoll, Gaute T
author_sort Mäki-Marttunen, Tuomo
collection PubMed
description Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.
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spelling pubmed-63191722019-01-10 Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations Mäki-Marttunen, Tuomo Krull, Florian Bettella, Francesco Hagen, Espen Næss, Solveig Ness, Torbjørn V Moberget, Torgeir Elvsåshagen, Torbjørn Metzner, Christoph Devor, Anna Edwards, Andrew G Fyhn, Marianne Djurovic, Srdjan Dale, Anders M Andreassen, Ole A Einevoll, Gaute T Cereb Cortex Original Articles Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia. Oxford University Press 2019-02 2018-11-22 /pmc/articles/PMC6319172/ /pubmed/30475994 http://dx.doi.org/10.1093/cercor/bhy291 Text en © The Author(s) 2018. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Mäki-Marttunen, Tuomo
Krull, Florian
Bettella, Francesco
Hagen, Espen
Næss, Solveig
Ness, Torbjørn V
Moberget, Torgeir
Elvsåshagen, Torbjørn
Metzner, Christoph
Devor, Anna
Edwards, Andrew G
Fyhn, Marianne
Djurovic, Srdjan
Dale, Anders M
Andreassen, Ole A
Einevoll, Gaute T
Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
title Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
title_full Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
title_fullStr Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
title_full_unstemmed Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
title_short Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
title_sort alterations in schizophrenia-associated genes can lead to increased power in delta oscillations
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319172/
https://www.ncbi.nlm.nih.gov/pubmed/30475994
http://dx.doi.org/10.1093/cercor/bhy291
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