Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction

Abstract Abnormalities in electroencephalographic (EEG) biomarkers occur in patients with schizophrenia and those clinically at high risk for transition to psychosis and are associated with cognitive impairment. Converging evidence suggests N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a...

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Autores principales:	David D. Aguilar, Leana K. Radzik, Felipe L. Schiffino, Oluwarotimi O. Folorunso, Mark R. Zielinski, Joseph T. Coyle, Darrick T. Balu, James M. McNally
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8ea1784276d4c4a8fbcc40d7b2e1e8c
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spelling	oai:doaj.org-article:f8ea1784276d4c4a8fbcc40d7b2e1e8c2021-12-02T13:41:34ZAltered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction10.1038/s41598-021-88428-92045-2322https://doaj.org/article/f8ea1784276d4c4a8fbcc40d7b2e1e8c2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88428-9https://doaj.org/toc/2045-2322Abstract Abnormalities in electroencephalographic (EEG) biomarkers occur in patients with schizophrenia and those clinically at high risk for transition to psychosis and are associated with cognitive impairment. Converging evidence suggests N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a central role in the pathophysiology of schizophrenia and likely contributes to biomarker impairments. Thus, characterizing these biomarkers is of significant interest for early diagnosis of schizophrenia and development of novel treatments. We utilized in vivo EEG recordings and behavioral analyses to perform a battery of electrophysiological biomarkers in an established model of chronic NMDAR hypofunction, serine racemase knockout (SRKO) mice, and their wild-type littermates. SRKO mice displayed impairments in investigation-elicited gamma power that corresponded with reduced short-term social recognition and enhanced background (pre-investigation) gamma activity. Additionally, SRKO mice exhibited sensory gating impairments in both evoked-gamma power and event-related potential amplitude. However, other biomarkers including the auditory steady-state response, sleep spindles, and state-specific power spectral density were generally neurotypical. In conclusion, SRKO mice demonstrate how chronic NMDAR hypofunction contributes to deficits in certain translationally-relevant EEG biomarkers altered in schizophrenia. Importantly, our gamma band findings suggest an aberrant signal-to-noise ratio impairing cognition that occurs with NMDAR hypofunction, potentially tied to impaired task-dependent alteration in functional connectivity.David D. AguilarLeana K. RadzikFelipe L. SchiffinoOluwarotimi O. FolorunsoMark R. ZielinskiJoseph T. CoyleDarrick T. BaluJames M. McNallyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David D. Aguilar Leana K. Radzik Felipe L. Schiffino Oluwarotimi O. Folorunso Mark R. Zielinski Joseph T. Coyle Darrick T. Balu James M. McNally Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction
description	Abstract Abnormalities in electroencephalographic (EEG) biomarkers occur in patients with schizophrenia and those clinically at high risk for transition to psychosis and are associated with cognitive impairment. Converging evidence suggests N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a central role in the pathophysiology of schizophrenia and likely contributes to biomarker impairments. Thus, characterizing these biomarkers is of significant interest for early diagnosis of schizophrenia and development of novel treatments. We utilized in vivo EEG recordings and behavioral analyses to perform a battery of electrophysiological biomarkers in an established model of chronic NMDAR hypofunction, serine racemase knockout (SRKO) mice, and their wild-type littermates. SRKO mice displayed impairments in investigation-elicited gamma power that corresponded with reduced short-term social recognition and enhanced background (pre-investigation) gamma activity. Additionally, SRKO mice exhibited sensory gating impairments in both evoked-gamma power and event-related potential amplitude. However, other biomarkers including the auditory steady-state response, sleep spindles, and state-specific power spectral density were generally neurotypical. In conclusion, SRKO mice demonstrate how chronic NMDAR hypofunction contributes to deficits in certain translationally-relevant EEG biomarkers altered in schizophrenia. Importantly, our gamma band findings suggest an aberrant signal-to-noise ratio impairing cognition that occurs with NMDAR hypofunction, potentially tied to impaired task-dependent alteration in functional connectivity.
format	article
author	David D. Aguilar Leana K. Radzik Felipe L. Schiffino Oluwarotimi O. Folorunso Mark R. Zielinski Joseph T. Coyle Darrick T. Balu James M. McNally
author_facet	David D. Aguilar Leana K. Radzik Felipe L. Schiffino Oluwarotimi O. Folorunso Mark R. Zielinski Joseph T. Coyle Darrick T. Balu James M. McNally
author_sort	David D. Aguilar
title	Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction
title_short	Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction
title_full	Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction
title_fullStr	Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction
title_full_unstemmed	Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction
title_sort	altered neural oscillations and behavior in a genetic mouse model of nmda receptor hypofunction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f8ea1784276d4c4a8fbcc40d7b2e1e8c
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Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction

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