Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors

Autores
Fernandez, Sebastian Pablo; Broussot, Loïc; Marti, Fabio; Contesse, Thomas; Mouska, Xavier; Soiza Reilly, Mariano; Marie, Hélène; Faure, Philippe; Barik, Jacques
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals remain largely unknown. We demonstrate that chronic social defeat (CSD) stress, a preclinical paradigm of depression, causes marked hyperactivity of laterodorsal tegmentum (LDTg) excitatory neurons that project to the VTA. Selective chemogenetic-mediated inhibition of cholinergic LDTg neurons prevent CSD-induced VTA DA neurons dysregulation and depressive-like behaviors. Pro-depressant outcomes are replicated by pairing activation of LDTg cholinergic terminals in the VTA with a moderate stress. Prevention of CSD outcomes are recapitulated by blocking corticotropin-releasing factor receptor 1 within the LDTg. These data uncover a neuro-circuitry of depressive-like disorders and demonstrate that stress, via a neuroendocrine signal, profoundly dysregulates the LDTg.
Fil: Fernandez, Sebastian Pablo. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Broussot, Loïc. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Marti, Fabio. Centre National de la Recherche Scientifique; Francia. Universite Pierre et Marie Curie; Francia
Fil: Contesse, Thomas. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Mouska, Xavier. Université Côte D'azur; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Soiza Reilly, Mariano. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Marie, Hélène. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Faure, Philippe. Centre National de la Recherche Scientifique; Francia. Universite Pierre et Marie Curie; Francia
Fil: Barik, Jacques. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Materia
Depression
VTA
Acetylcholine
CRF
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:11336/88531
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/88531
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviorsFernandez, Sebastian PabloBroussot, LoïcMarti, FabioContesse, ThomasMouska, XavierSoiza Reilly, MarianoMarie, HélèneFaure, PhilippeBarik, JacquesDepressionVTAAcetylcholineCRFhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals remain largely unknown. We demonstrate that chronic social defeat (CSD) stress, a preclinical paradigm of depression, causes marked hyperactivity of laterodorsal tegmentum (LDTg) excitatory neurons that project to the VTA. Selective chemogenetic-mediated inhibition of cholinergic LDTg neurons prevent CSD-induced VTA DA neurons dysregulation and depressive-like behaviors. Pro-depressant outcomes are replicated by pairing activation of LDTg cholinergic terminals in the VTA with a moderate stress. Prevention of CSD outcomes are recapitulated by blocking corticotropin-releasing factor receptor 1 within the LDTg. These data uncover a neuro-circuitry of depressive-like disorders and demonstrate that stress, via a neuroendocrine signal, profoundly dysregulates the LDTg.Fil: Fernandez, Sebastian Pablo. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; FranciaFil: Broussot, Loïc. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; FranciaFil: Marti, Fabio. Centre National de la Recherche Scientifique; Francia. Universite Pierre et Marie Curie; FranciaFil: Contesse, Thomas. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; FranciaFil: Mouska, Xavier. Université Côte D'azur; Francia. Centre National de la Recherche Scientifique; FranciaFil: Soiza Reilly, Mariano. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Marie, Hélène. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; FranciaFil: Faure, Philippe. Centre National de la Recherche Scientifique; Francia. Universite Pierre et Marie Curie; FranciaFil: Barik, Jacques. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; FranciaNature2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88531Fernandez, Sebastian Pablo; Broussot, Loïc; Marti, Fabio; Contesse, Thomas; Mouska, Xavier; et al.; Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors; Nature; Nature Communications; 9; 4449; 12-2018; 1-122041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-018-06809-7info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-018-06809-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:22:22Zoai:ri.conicet.gov.ar:11336/88531instacron: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 10:22:22.562CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
title Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
spellingShingle Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
Fernandez, Sebastian Pablo
Depression
VTA
Acetylcholine
CRF
title_short Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
title_full Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
title_fullStr Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
title_full_unstemmed Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
title_sort Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
dc.creator.none.fl_str_mv Fernandez, Sebastian Pablo
Broussot, Loïc
Marti, Fabio
Contesse, Thomas
Mouska, Xavier
Soiza Reilly, Mariano
Marie, Hélène
Faure, Philippe
Barik, Jacques
author Fernandez, Sebastian Pablo
author_facet Fernandez, Sebastian Pablo
Broussot, Loïc
Marti, Fabio
Contesse, Thomas
Mouska, Xavier
Soiza Reilly, Mariano
Marie, Hélène
Faure, Philippe
Barik, Jacques
author_role author
author2 Broussot, Loïc
Marti, Fabio
Contesse, Thomas
Mouska, Xavier
Soiza Reilly, Mariano
Marie, Hélène
Faure, Philippe
Barik, Jacques
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Depression
VTA
Acetylcholine
CRF
topic Depression
VTA
Acetylcholine
CRF
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals remain largely unknown. We demonstrate that chronic social defeat (CSD) stress, a preclinical paradigm of depression, causes marked hyperactivity of laterodorsal tegmentum (LDTg) excitatory neurons that project to the VTA. Selective chemogenetic-mediated inhibition of cholinergic LDTg neurons prevent CSD-induced VTA DA neurons dysregulation and depressive-like behaviors. Pro-depressant outcomes are replicated by pairing activation of LDTg cholinergic terminals in the VTA with a moderate stress. Prevention of CSD outcomes are recapitulated by blocking corticotropin-releasing factor receptor 1 within the LDTg. These data uncover a neuro-circuitry of depressive-like disorders and demonstrate that stress, via a neuroendocrine signal, profoundly dysregulates the LDTg.
Fil: Fernandez, Sebastian Pablo. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Broussot, Loïc. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Marti, Fabio. Centre National de la Recherche Scientifique; Francia. Universite Pierre et Marie Curie; Francia
Fil: Contesse, Thomas. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Mouska, Xavier. Université Côte D'azur; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Soiza Reilly, Mariano. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Marie, Hélène. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
Fil: Faure, Philippe. Centre National de la Recherche Scientifique; Francia. Universite Pierre et Marie Curie; Francia
Fil: Barik, Jacques. Centre National de la Recherche Scientifique; Francia. Université Côte D'azur; Francia
description Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals remain largely unknown. We demonstrate that chronic social defeat (CSD) stress, a preclinical paradigm of depression, causes marked hyperactivity of laterodorsal tegmentum (LDTg) excitatory neurons that project to the VTA. Selective chemogenetic-mediated inhibition of cholinergic LDTg neurons prevent CSD-induced VTA DA neurons dysregulation and depressive-like behaviors. Pro-depressant outcomes are replicated by pairing activation of LDTg cholinergic terminals in the VTA with a moderate stress. Prevention of CSD outcomes are recapitulated by blocking corticotropin-releasing factor receptor 1 within the LDTg. These data uncover a neuro-circuitry of depressive-like disorders and demonstrate that stress, via a neuroendocrine signal, profoundly dysregulates the LDTg.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/88531
Fernandez, Sebastian Pablo; Broussot, Loïc; Marti, Fabio; Contesse, Thomas; Mouska, Xavier; et al.; Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors; Nature; Nature Communications; 9; 4449; 12-2018; 1-12
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88531
identifier_str_mv Fernandez, Sebastian Pablo; Broussot, Loïc; Marti, Fabio; Contesse, Thomas; Mouska, Xavier; et al.; Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors; Nature; Nature Communications; 9; 4449; 12-2018; 1-12
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-018-06809-7
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-018-06809-7
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
publisher.none.fl_str_mv Nature
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
_version_ 1844614214894747648
score 13.070432

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