Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes

Autores
Belforte, Juan Emilio; Zsiros, Veronika; Sklar, Elyse R; Jiang, Zhihong; Yu, Gu; Li, Yuqing; Quinlan, Elizabeth M; Nakazawa, Kazu
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40–50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.
Fil: Belforte, Juan Emilio. Wayne State University; Estados Unidos. National Institute of Mental Health; Estados Unidos. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zsiros, Veronika. National Institute of Mental Health; Estados Unidos
Fil: Sklar, Elyse R. National Institute of Mental Health; Estados Unidos. Wayne State University; Estados Unidos
Fil: Jiang, Zhihong. National Institute of Mental Health; Estados Unidos
Fil: Yu, Gu. University of Maryland; Estados Unidos
Fil: Li, Yuqing. University of Alabama at Birmingahm; Estados Unidos
Fil: Quinlan, Elizabeth M. University of Maryland; Estados Unidos
Fil: Nakazawa, Kazu. National Institute of Mental Health; Estados Unidos
Materia
esquizofrenia
nmda
interneuronas
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96174
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypesBelforte, Juan EmilioZsiros, VeronikaSklar, Elyse RJiang, ZhihongYu, GuLi, YuqingQuinlan, Elizabeth MNakazawa, Kazuesquizofrenianmdainterneuronashttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40–50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.Fil: Belforte, Juan Emilio. Wayne State University; Estados Unidos. National Institute of Mental Health; Estados Unidos. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zsiros, Veronika. National Institute of Mental Health; Estados UnidosFil: Sklar, Elyse R. National Institute of Mental Health; Estados Unidos. Wayne State University; Estados UnidosFil: Jiang, Zhihong. National Institute of Mental Health; Estados UnidosFil: Yu, Gu. University of Maryland; Estados UnidosFil: Li, Yuqing. University of Alabama at Birmingahm; Estados UnidosFil: Quinlan, Elizabeth M. University of Maryland; Estados UnidosFil: Nakazawa, Kazu. National Institute of Mental Health; Estados UnidosNature Publishing Group2009-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96174Belforte, Juan Emilio; Zsiros, Veronika; Sklar, Elyse R; Jiang, Zhihong; Yu, Gu; et al.; Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes; Nature Publishing Group; Nature Neuroscience.; 13; 1; 11-2009; 76-831097-6256CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797836/info:eu-repo/semantics/altIdentifier/doi/10.1038%2Fnn.2447info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.2447info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:19:06Zoai:ri.conicet.gov.ar:11336/96174instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 11:19:06.731CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
title Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
spellingShingle Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
Belforte, Juan Emilio
esquizofrenia
nmda
interneuronas
title_short Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
title_full Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
title_fullStr Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
title_full_unstemmed Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
title_sort Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
dc.creator.none.fl_str_mv Belforte, Juan Emilio
Zsiros, Veronika
Sklar, Elyse R
Jiang, Zhihong
Yu, Gu
Li, Yuqing
Quinlan, Elizabeth M
Nakazawa, Kazu
author Belforte, Juan Emilio
author_facet Belforte, Juan Emilio
Zsiros, Veronika
Sklar, Elyse R
Jiang, Zhihong
Yu, Gu
Li, Yuqing
Quinlan, Elizabeth M
Nakazawa, Kazu
author_role author
author2 Zsiros, Veronika
Sklar, Elyse R
Jiang, Zhihong
Yu, Gu
Li, Yuqing
Quinlan, Elizabeth M
Nakazawa, Kazu
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv esquizofrenia
nmda
interneuronas
topic esquizofrenia
nmda
interneuronas
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40–50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.
Fil: Belforte, Juan Emilio. Wayne State University; Estados Unidos. National Institute of Mental Health; Estados Unidos. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zsiros, Veronika. National Institute of Mental Health; Estados Unidos
Fil: Sklar, Elyse R. National Institute of Mental Health; Estados Unidos. Wayne State University; Estados Unidos
Fil: Jiang, Zhihong. National Institute of Mental Health; Estados Unidos
Fil: Yu, Gu. University of Maryland; Estados Unidos
Fil: Li, Yuqing. University of Alabama at Birmingahm; Estados Unidos
Fil: Quinlan, Elizabeth M. University of Maryland; Estados Unidos
Fil: Nakazawa, Kazu. National Institute of Mental Health; Estados Unidos
description Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40–50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/96174
Belforte, Juan Emilio; Zsiros, Veronika; Sklar, Elyse R; Jiang, Zhihong; Yu, Gu; et al.; Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes; Nature Publishing Group; Nature Neuroscience.; 13; 1; 11-2009; 76-83
1097-6256
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96174
identifier_str_mv Belforte, Juan Emilio; Zsiros, Veronika; Sklar, Elyse R; Jiang, Zhihong; Yu, Gu; et al.; Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes; Nature Publishing Group; Nature Neuroscience.; 13; 1; 11-2009; 76-83
1097-6256
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797836/
info:eu-repo/semantics/altIdentifier/doi/10.1038%2Fnn.2447
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.2447
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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