Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Autores
Hutchison, M. A.; Gu, X.; Adrover, Martín Federico; Lee, M. R.; Hnasko, T. S.; Alvarez, V. A.; Lu, W.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.
Fil: Hutchison, M. A.. National Institutes of Health; Estados Unidos
Fil: Gu, X.. National Institutes of Health; Estados Unidos
Fil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lee, M. R.. National Institutes of Health; Estados Unidos
Fil: Hnasko, T. S.. University of California at San Diego; Estados Unidos
Fil: Alvarez, V. A.. National Institutes of Health; Estados Unidos
Fil: Lu, W.. National Institutes of Health; Estados Unidos
Materia
MIDBRAIN
DOPAMINE NEURONS
GLUTAMATE RECEPTORS
BEHAVIOR
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:11336/79844
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behaviorHutchison, M. A.Gu, X.Adrover, Martín FedericoLee, M. R.Hnasko, T. S.Alvarez, V. A.Lu, W.MIDBRAINDOPAMINE NEURONSGLUTAMATE RECEPTORSBEHAVIORhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados UnidosNature Publishing Group2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79844Hutchison, M. A.; Gu, X.; Adrover, Martín Federico; Lee, M. R.; Hnasko, T. S.; et al.; Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior; Nature Publishing Group; Molecular Psychiatry; 23; 5; 5-2018; 1213-12251359-4184CONICET DigitalCONICETengCorrección: https://www.nature.com/articles/mp20183info:eu-repo/semantics/altIdentifier/doi/10.1038/mp.2017.7info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/mp20177info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28194005/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:19Zoai:ri.conicet.gov.ar:11336/79844instacron: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 10:18:19.498CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
title Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
spellingShingle Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
Hutchison, M. A.
MIDBRAIN
DOPAMINE NEURONS
GLUTAMATE RECEPTORS
BEHAVIOR
title_short Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
title_full Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
title_fullStr Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
title_full_unstemmed Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
title_sort Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
dc.creator.none.fl_str_mv Hutchison, M. A.
Gu, X.
Adrover, Martín Federico
Lee, M. R.
Hnasko, T. S.
Alvarez, V. A.
Lu, W.
author Hutchison, M. A.
author_facet Hutchison, M. A.
Gu, X.
Adrover, Martín Federico
Lee, M. R.
Hnasko, T. S.
Alvarez, V. A.
Lu, W.
author_role author
author2 Gu, X.
Adrover, Martín Federico
Lee, M. R.
Hnasko, T. S.
Alvarez, V. A.
Lu, W.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv MIDBRAIN
DOPAMINE NEURONS
GLUTAMATE RECEPTORS
BEHAVIOR
topic MIDBRAIN
DOPAMINE NEURONS
GLUTAMATE RECEPTORS
BEHAVIOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.
Fil: Hutchison, M. A.. National Institutes of Health; Estados Unidos
Fil: Gu, X.. National Institutes of Health; Estados Unidos
Fil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lee, M. R.. National Institutes of Health; Estados Unidos
Fil: Hnasko, T. S.. University of California at San Diego; Estados Unidos
Fil: Alvarez, V. A.. National Institutes of Health; Estados Unidos
Fil: Lu, W.. National Institutes of Health; Estados Unidos
description Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
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/11336/79844
Hutchison, M. A.; Gu, X.; Adrover, Martín Federico; Lee, M. R.; Hnasko, T. S.; et al.; Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior; Nature Publishing Group; Molecular Psychiatry; 23; 5; 5-2018; 1213-1225
1359-4184
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79844
identifier_str_mv Hutchison, M. A.; Gu, X.; Adrover, Martín Federico; Lee, M. R.; Hnasko, T. S.; et al.; Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior; Nature Publishing Group; Molecular Psychiatry; 23; 5; 5-2018; 1213-1225
1359-4184
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Corrección: https://www.nature.com/articles/mp20183
info:eu-repo/semantics/altIdentifier/doi/10.1038/mp.2017.7
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/mp20177
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28194005/
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 13.070432

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