Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schi...

Autores
Pafundo, Diego Esteban; Pretell Annan, Carlos Alfredo; Fulginiti, Nicolás Marcelo; Belforte, Juan Emilio
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Altered Excitatory/Inhibitory (E/I) balance of cortical synaptic inputs has been proposed as a central pathophysiological factor for psychiatric neurodevelopmental disorders, including schizophrenia (SZ). However, direct measurement of E/I synaptic balance have not been assessed in vivo for any validated SZ animal model. Using a mouse model useful for the study of SZ we show that a selective ablation of NMDA receptors (NMDAr) in cortical and hippocampal interneurons during early postnatal development results in an E/I imbalance in vivo, with synaptic inputs to pyramidal neurons shifted towards excitation in the adult mutant medial prefrontal cortex (mPFC). Remarkably, this imbalance depends on the cortical state, only emerging when theta and gamma oscillations are predominant in the network. Additional brain slice recordings and subsequent 3D morphological reconstruction showed that E/I imbalance emerges after adolescence concomitantly with significant dendritic retraction and dendritic spine re-localization in pyramidal neurons. Therefore, early postnatal ablation of NMDAr in cortical and hippocampal interneurons developmentally impacts on E/I imbalance in vivo in an activity-dependent manner.
Fil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pretell Annan, Carlos Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Fulginiti, Nicolás Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
ADOLESCENCE
DENDRITIC RETRACTION
ELECTROPHYSIOLOGY
GAMMA OSCILLATIONS
PARVALBUMIN
PREFRONTAL CORTEX
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:11336/172288
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/172288
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophreniaPafundo, Diego EstebanPretell Annan, Carlos AlfredoFulginiti, Nicolás MarceloBelforte, Juan EmilioADOLESCENCEDENDRITIC RETRACTIONELECTROPHYSIOLOGYGAMMA OSCILLATIONSPARVALBUMINPREFRONTAL CORTEXhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Altered Excitatory/Inhibitory (E/I) balance of cortical synaptic inputs has been proposed as a central pathophysiological factor for psychiatric neurodevelopmental disorders, including schizophrenia (SZ). However, direct measurement of E/I synaptic balance have not been assessed in vivo for any validated SZ animal model. Using a mouse model useful for the study of SZ we show that a selective ablation of NMDA receptors (NMDAr) in cortical and hippocampal interneurons during early postnatal development results in an E/I imbalance in vivo, with synaptic inputs to pyramidal neurons shifted towards excitation in the adult mutant medial prefrontal cortex (mPFC). Remarkably, this imbalance depends on the cortical state, only emerging when theta and gamma oscillations are predominant in the network. Additional brain slice recordings and subsequent 3D morphological reconstruction showed that E/I imbalance emerges after adolescence concomitantly with significant dendritic retraction and dendritic spine re-localization in pyramidal neurons. Therefore, early postnatal ablation of NMDAr in cortical and hippocampal interneurons developmentally impacts on E/I imbalance in vivo in an activity-dependent manner.Fil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pretell Annan, Carlos Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Fulginiti, Nicolás Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaOxford University Press2021-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/172288Pafundo, Diego Esteban; Pretell Annan, Carlos Alfredo; Fulginiti, Nicolás Marcelo; Belforte, Juan Emilio; Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia; Oxford University Press; Schizophrenia Bulletin; 47; 5; 9-2021; 1300-13090586-7614CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/schizophreniabulletin/article/47/5/1300/6209884info:eu-repo/semantics/altIdentifier/doi/10.1093/schbul/sbab030info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:46:23Zoai:ri.conicet.gov.ar:11336/172288instacron: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:34982025-09-29 10:46:23.914CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
title Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
spellingShingle Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
Pafundo, Diego Esteban
ADOLESCENCE
DENDRITIC RETRACTION
ELECTROPHYSIOLOGY
GAMMA OSCILLATIONS
PARVALBUMIN
PREFRONTAL CORTEX
title_short Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
title_full Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
title_fullStr Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
title_full_unstemmed Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
title_sort Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia
dc.creator.none.fl_str_mv Pafundo, Diego Esteban
Pretell Annan, Carlos Alfredo
Fulginiti, Nicolás Marcelo
Belforte, Juan Emilio
author Pafundo, Diego Esteban
author_facet Pafundo, Diego Esteban
Pretell Annan, Carlos Alfredo
Fulginiti, Nicolás Marcelo
Belforte, Juan Emilio
author_role author
author2 Pretell Annan, Carlos Alfredo
Fulginiti, Nicolás Marcelo
Belforte, Juan Emilio
author2_role author
author
author
dc.subject.none.fl_str_mv ADOLESCENCE
DENDRITIC RETRACTION
ELECTROPHYSIOLOGY
GAMMA OSCILLATIONS
PARVALBUMIN
PREFRONTAL CORTEX
topic ADOLESCENCE
DENDRITIC RETRACTION
ELECTROPHYSIOLOGY
GAMMA OSCILLATIONS
PARVALBUMIN
PREFRONTAL CORTEX
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Altered Excitatory/Inhibitory (E/I) balance of cortical synaptic inputs has been proposed as a central pathophysiological factor for psychiatric neurodevelopmental disorders, including schizophrenia (SZ). However, direct measurement of E/I synaptic balance have not been assessed in vivo for any validated SZ animal model. Using a mouse model useful for the study of SZ we show that a selective ablation of NMDA receptors (NMDAr) in cortical and hippocampal interneurons during early postnatal development results in an E/I imbalance in vivo, with synaptic inputs to pyramidal neurons shifted towards excitation in the adult mutant medial prefrontal cortex (mPFC). Remarkably, this imbalance depends on the cortical state, only emerging when theta and gamma oscillations are predominant in the network. Additional brain slice recordings and subsequent 3D morphological reconstruction showed that E/I imbalance emerges after adolescence concomitantly with significant dendritic retraction and dendritic spine re-localization in pyramidal neurons. Therefore, early postnatal ablation of NMDAr in cortical and hippocampal interneurons developmentally impacts on E/I imbalance in vivo in an activity-dependent manner.
Fil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pretell Annan, Carlos Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Fulginiti, Nicolás Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description Altered Excitatory/Inhibitory (E/I) balance of cortical synaptic inputs has been proposed as a central pathophysiological factor for psychiatric neurodevelopmental disorders, including schizophrenia (SZ). However, direct measurement of E/I synaptic balance have not been assessed in vivo for any validated SZ animal model. Using a mouse model useful for the study of SZ we show that a selective ablation of NMDA receptors (NMDAr) in cortical and hippocampal interneurons during early postnatal development results in an E/I imbalance in vivo, with synaptic inputs to pyramidal neurons shifted towards excitation in the adult mutant medial prefrontal cortex (mPFC). Remarkably, this imbalance depends on the cortical state, only emerging when theta and gamma oscillations are predominant in the network. Additional brain slice recordings and subsequent 3D morphological reconstruction showed that E/I imbalance emerges after adolescence concomitantly with significant dendritic retraction and dendritic spine re-localization in pyramidal neurons. Therefore, early postnatal ablation of NMDAr in cortical and hippocampal interneurons developmentally impacts on E/I imbalance in vivo in an activity-dependent manner.
publishDate 2021
dc.date.none.fl_str_mv 2021-09
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/11336/172288
Pafundo, Diego Esteban; Pretell Annan, Carlos Alfredo; Fulginiti, Nicolás Marcelo; Belforte, Juan Emilio; Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia; Oxford University Press; Schizophrenia Bulletin; 47; 5; 9-2021; 1300-1309
0586-7614
CONICET Digital
CONICET
url http://hdl.handle.net/11336/172288
identifier_str_mv Pafundo, Diego Esteban; Pretell Annan, Carlos Alfredo; Fulginiti, Nicolás Marcelo; Belforte, Juan Emilio; Early NMDA receptor ablation in interneurons causes an activity-dependent E/I imbalance in vivo in prefrontal cortex pyramidal neurons of a mouse model useful for the study of schizophrenia; Oxford University Press; Schizophrenia Bulletin; 47; 5; 9-2021; 1300-1309
0586-7614
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://academic.oup.com/schizophreniabulletin/article/47/5/1300/6209884
info:eu-repo/semantics/altIdentifier/doi/10.1093/schbul/sbab030
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 Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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