Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells

Abstract A hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largel...

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Autores principales:	Kasyoka Kilonzo, Bastiaan van der Veen, Jasper Teutsch, Stefanie Schulz, Sampath K. T. Kapanaiah, Birgit Liss, Dennis Kätzel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/34948e7f5a9c4290958085c57becf0fc
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spelling	oai:doaj.org-article:34948e7f5a9c4290958085c57becf0fc2021-12-02T16:45:47ZDelayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells10.1038/s41598-021-88200-z2045-2322https://doaj.org/article/34948e7f5a9c4290958085c57becf0fc2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88200-zhttps://doaj.org/toc/2045-2322Abstract A hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largely unknown. One pharmaco-resistant core symptom of schizophrenia is impaired working memory (WM). NMDARs have been suggested to mediate sustained firing in excitatory neurons of the prefrontal cortex (PFC) that might underlie WM storage. However, if NMDAR-hypofunction in prefrontal excitatory neurons may indeed entail WM impairments is unknown. We here investigated this question in mice, in which NMDARs were genetically-ablated in PFC excitatory cells. This cell type-selective NMDAR-hypofunction caused a specific deficit in a delayed-matching-to-position (DMTP) 5-choice-based operant WM task. In contrast, T-maze rewarded alternation and several psychological functions including attention, spatial short-term habituation, novelty-processing, motivation, sociability, impulsivity, and hedonic valuation remained unimpaired at the level of GluN1-hypofunction caused by our manipulation. Our data suggest that a hypofunction of NMDARs in prefrontal excitatory neurons may indeed cause WM impairments, but are possibly not accounting for most other deficits in schizophrenia.Kasyoka KilonzoBastiaan van der VeenJasper TeutschStefanie SchulzSampath K. T. KapanaiahBirgit LissDennis KätzelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kasyoka Kilonzo Bastiaan van der Veen Jasper Teutsch Stefanie Schulz Sampath K. T. Kapanaiah Birgit Liss Dennis Kätzel Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells
description	Abstract A hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largely unknown. One pharmaco-resistant core symptom of schizophrenia is impaired working memory (WM). NMDARs have been suggested to mediate sustained firing in excitatory neurons of the prefrontal cortex (PFC) that might underlie WM storage. However, if NMDAR-hypofunction in prefrontal excitatory neurons may indeed entail WM impairments is unknown. We here investigated this question in mice, in which NMDARs were genetically-ablated in PFC excitatory cells. This cell type-selective NMDAR-hypofunction caused a specific deficit in a delayed-matching-to-position (DMTP) 5-choice-based operant WM task. In contrast, T-maze rewarded alternation and several psychological functions including attention, spatial short-term habituation, novelty-processing, motivation, sociability, impulsivity, and hedonic valuation remained unimpaired at the level of GluN1-hypofunction caused by our manipulation. Our data suggest that a hypofunction of NMDARs in prefrontal excitatory neurons may indeed cause WM impairments, but are possibly not accounting for most other deficits in schizophrenia.
format	article
author	Kasyoka Kilonzo Bastiaan van der Veen Jasper Teutsch Stefanie Schulz Sampath K. T. Kapanaiah Birgit Liss Dennis Kätzel
author_facet	Kasyoka Kilonzo Bastiaan van der Veen Jasper Teutsch Stefanie Schulz Sampath K. T. Kapanaiah Birgit Liss Dennis Kätzel
author_sort	Kasyoka Kilonzo
title	Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells
title_short	Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells
title_full	Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells
title_fullStr	Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells
title_full_unstemmed	Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells
title_sort	delayed-matching-to-position working memory in mice relies on nmda-receptors in prefrontal pyramidal cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/34948e7f5a9c4290958085c57becf0fc
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Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells

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