Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons

Autores
Martos Schott, Yanina Victoria; Braz, Bárbara Yael; Beccaria, Juan Pablo; Murer, Mario Gustavo; Belforte, Juan Emilio
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mechanisms underlying social dysfunction in neuropsychiatric conditions like obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) remain uncertain. Dysfunctions in basal ganglia, including reduced number of striatal cholinergic interneurons (SCIN), have been involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type and region specific manner. Mice were subjected to an extensive behavioral testing including assessment of social behaviors and corticostriatal functional connectivity was evaluated in vivo. Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally-driven, but not self-directed, repetitive behaviors are exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation the normal pattern of social exploration is continuously replayed. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors including social related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that impact on social performance providing a link between SCIN dysfunction and social impairments present in psychiatric disorders.
Fil: Martos Schott, Yanina Victoria. 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: Braz, Bárbara Yael. 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: Beccaria, Juan Pablo. 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: Murer, Mario Gustavo. 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
Cholinergic Interneurons
Corticostriatal Connectivity
Genetic Ablation
Mice
Social Behavior
Striatum
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:11336/47462
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47462
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic InterneuronsMartos Schott, Yanina VictoriaBraz, Bárbara YaelBeccaria, Juan PabloMurer, Mario GustavoBelforte, Juan EmilioCholinergic InterneuronsCorticostriatal ConnectivityGenetic AblationMiceSocial BehaviorStriatumhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The mechanisms underlying social dysfunction in neuropsychiatric conditions like obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) remain uncertain. Dysfunctions in basal ganglia, including reduced number of striatal cholinergic interneurons (SCIN), have been involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type and region specific manner. Mice were subjected to an extensive behavioral testing including assessment of social behaviors and corticostriatal functional connectivity was evaluated in vivo. Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally-driven, but not self-directed, repetitive behaviors are exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation the normal pattern of social exploration is continuously replayed. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors including social related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that impact on social performance providing a link between SCIN dysfunction and social impairments present in psychiatric disorders.Fil: Martos Schott, Yanina Victoria. 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: Braz, Bárbara Yael. 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: Beccaria, Juan Pablo. 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: Murer, Mario Gustavo. 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; ArgentinaSociety for Neuroscience2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47462Martos Schott, Yanina Victoria; Braz, Bárbara Yael; Beccaria, Juan Pablo; Murer, Mario Gustavo; Belforte, Juan Emilio; Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons; Society for Neuroscience; Journal of Neuroscience; 37; 11; 3-2017; 2849-28580270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.3460-16.2017info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/early/2017/02/13/JNEUROSCI.3460-16.2017info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:06Zoai:ri.conicet.gov.ar:11336/47462instacron: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 09:43:06.88CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
title Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
spellingShingle Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
Martos Schott, Yanina Victoria
Cholinergic Interneurons
Corticostriatal Connectivity
Genetic Ablation
Mice
Social Behavior
Striatum
title_short Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
title_full Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
title_fullStr Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
title_full_unstemmed Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
title_sort Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons
dc.creator.none.fl_str_mv Martos Schott, Yanina Victoria
Braz, Bárbara Yael
Beccaria, Juan Pablo
Murer, Mario Gustavo
Belforte, Juan Emilio
author Martos Schott, Yanina Victoria
author_facet Martos Schott, Yanina Victoria
Braz, Bárbara Yael
Beccaria, Juan Pablo
Murer, Mario Gustavo
Belforte, Juan Emilio
author_role author
author2 Braz, Bárbara Yael
Beccaria, Juan Pablo
Murer, Mario Gustavo
Belforte, Juan Emilio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Cholinergic Interneurons
Corticostriatal Connectivity
Genetic Ablation
Mice
Social Behavior
Striatum
topic Cholinergic Interneurons
Corticostriatal Connectivity
Genetic Ablation
Mice
Social Behavior
Striatum
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The mechanisms underlying social dysfunction in neuropsychiatric conditions like obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) remain uncertain. Dysfunctions in basal ganglia, including reduced number of striatal cholinergic interneurons (SCIN), have been involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type and region specific manner. Mice were subjected to an extensive behavioral testing including assessment of social behaviors and corticostriatal functional connectivity was evaluated in vivo. Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally-driven, but not self-directed, repetitive behaviors are exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation the normal pattern of social exploration is continuously replayed. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors including social related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that impact on social performance providing a link between SCIN dysfunction and social impairments present in psychiatric disorders.
Fil: Martos Schott, Yanina Victoria. 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: Braz, Bárbara Yael. 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: Beccaria, Juan Pablo. 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: Murer, Mario Gustavo. 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 The mechanisms underlying social dysfunction in neuropsychiatric conditions like obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) remain uncertain. Dysfunctions in basal ganglia, including reduced number of striatal cholinergic interneurons (SCIN), have been involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type and region specific manner. Mice were subjected to an extensive behavioral testing including assessment of social behaviors and corticostriatal functional connectivity was evaluated in vivo. Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally-driven, but not self-directed, repetitive behaviors are exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation the normal pattern of social exploration is continuously replayed. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors including social related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that impact on social performance providing a link between SCIN dysfunction and social impairments present in psychiatric disorders.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
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/11336/47462
Martos Schott, Yanina Victoria; Braz, Bárbara Yael; Beccaria, Juan Pablo; Murer, Mario Gustavo; Belforte, Juan Emilio; Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons; Society for Neuroscience; Journal of Neuroscience; 37; 11; 3-2017; 2849-2858
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47462
identifier_str_mv Martos Schott, Yanina Victoria; Braz, Bárbara Yael; Beccaria, Juan Pablo; Murer, Mario Gustavo; Belforte, Juan Emilio; Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons; Society for Neuroscience; Journal of Neuroscience; 37; 11; 3-2017; 2849-2858
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.3460-16.2017
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/early/2017/02/13/JNEUROSCI.3460-16.2017
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
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 13.069144

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