Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine

Autores
Dobbs, Lauren K.; Kaplan, Alanna R.; Lemos, Julia C.; Matsui, Aya; Rubinstein, Marcelo; Alvarez, Veronica A.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response.
Fil: Dobbs, Lauren K.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Kaplan, Alanna R.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Lemos, Julia C.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Matsui, Aya. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Michigan State University; Estados Unidos
Fil: Alvarez, Veronica A.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Materia
Dopamina
Estriado
Cocaina
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:11336/39123
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of CocaineDobbs, Lauren K.Kaplan, Alanna R.Lemos, Julia C.Matsui, AyaRubinstein, MarceloAlvarez, Veronica A.DopaminaEstriadoCocainahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response.Fil: Dobbs, Lauren K.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados UnidosFil: Kaplan, Alanna R.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados UnidosFil: Lemos, Julia C.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados UnidosFil: Matsui, Aya. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Michigan State University; Estados UnidosFil: Alvarez, Veronica A.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados UnidosCell Press2016-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39123Dobbs, Lauren K.; Kaplan, Alanna R.; Lemos, Julia C.; Matsui, Aya; Rubinstein, Marcelo; et al.; Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine; Cell Press; Neuron; 90; 5; 6-2016; 1100-11130896-6273CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuron.2016.04.031info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0896627316301180info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891261/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 Técnicas2025-09-29T09:54:21Zoai:ri.conicet.gov.ar:11336/39123instacron: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 09:54:21.992CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
title Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
spellingShingle Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
Dobbs, Lauren K.
Dopamina
Estriado
Cocaina
title_short Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
title_full Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
title_fullStr Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
title_full_unstemmed Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
title_sort Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
dc.creator.none.fl_str_mv Dobbs, Lauren K.
Kaplan, Alanna R.
Lemos, Julia C.
Matsui, Aya
Rubinstein, Marcelo
Alvarez, Veronica A.
author Dobbs, Lauren K.
author_facet Dobbs, Lauren K.
Kaplan, Alanna R.
Lemos, Julia C.
Matsui, Aya
Rubinstein, Marcelo
Alvarez, Veronica A.
author_role author
author2 Kaplan, Alanna R.
Lemos, Julia C.
Matsui, Aya
Rubinstein, Marcelo
Alvarez, Veronica A.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Dopamina
Estriado
Cocaina
topic Dopamina
Estriado
Cocaina
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response.
Fil: Dobbs, Lauren K.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Kaplan, Alanna R.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Lemos, Julia C.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Matsui, Aya. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Michigan State University; Estados Unidos
Fil: Alvarez, Veronica A.. National Institute on Alcohol Abuse and Alcoholism. Bethesda; Estados Unidos
description Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response.
publishDate 2016
dc.date.none.fl_str_mv 2016-06
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/11336/39123
Dobbs, Lauren K.; Kaplan, Alanna R.; Lemos, Julia C.; Matsui, Aya; Rubinstein, Marcelo; et al.; Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine; Cell Press; Neuron; 90; 5; 6-2016; 1100-1113
0896-6273
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39123
identifier_str_mv Dobbs, Lauren K.; Kaplan, Alanna R.; Lemos, Julia C.; Matsui, Aya; Rubinstein, Marcelo; et al.; Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine; Cell Press; Neuron; 90; 5; 6-2016; 1100-1113
0896-6273
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuron.2016.04.031
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0896627316301180
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891261/
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
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell 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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score 13.070432

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