Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors

Dopamine (DA) release in striatal circuits, including the nucleus accumbens medial shell (mNAcSh), tracks separable features of reward like motivation and reinforcement. However, the cellular and circuit mechanisms by which DA receptors transform DA release into distinct constructs of reward remain...

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Detalles Bibliográficos
Autores: Enriquez-Traba, Juan, Arenivar, Miguel, Yarur-Castillo, Hector E, Noh, Chloe, Flores, Rodolfo J, Weil, Tenley, Roy, Snehashis, Usdin, Ted B, LaGamma, Christina T, Wang, Huikun, Tsai, Valerie S, Kerspern, Damien, Moritz, Amy E, Sibley, David R, Lutas, Andrew, Moratalla, Rosario, Freyberg, Zachary, Tejeda, Hugo A
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/403810
Acceso en línea:http://hdl.handle.net/10261/403810
https://api.elsevier.com/content/abstract/scopus_id/85211921464
Access Level:acceso abierto
Palabra clave:http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
id ES_8bc60ff2db3edff5fb1b0e83d16cdb95
oai_identifier_str oai:digital.csic.es:10261/403810
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
title Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
spellingShingle Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
Enriquez-Traba, Juan
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
title_short Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
title_full Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
title_fullStr Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
title_full_unstemmed Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
title_sort Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
dc.creator.none.fl_str_mv Enriquez-Traba, Juan
Arenivar, Miguel
Yarur-Castillo, Hector E
Noh, Chloe
Flores, Rodolfo J
Weil, Tenley
Roy, Snehashis
Usdin, Ted B
LaGamma, Christina T
Wang, Huikun
Tsai, Valerie S
Kerspern, Damien
Moritz, Amy E
Sibley, David R
Lutas, Andrew
Moratalla, Rosario
Freyberg, Zachary
Tejeda, Hugo A
author Enriquez-Traba, Juan
author_facet Enriquez-Traba, Juan
Arenivar, Miguel
Yarur-Castillo, Hector E
Noh, Chloe
Flores, Rodolfo J
Weil, Tenley
Roy, Snehashis
Usdin, Ted B
LaGamma, Christina T
Wang, Huikun
Tsai, Valerie S
Kerspern, Damien
Moritz, Amy E
Sibley, David R
Lutas, Andrew
Moratalla, Rosario
Freyberg, Zachary
Tejeda, Hugo A
author_role author
author2 Arenivar, Miguel
Yarur-Castillo, Hector E
Noh, Chloe
Flores, Rodolfo J
Weil, Tenley
Roy, Snehashis
Usdin, Ted B
LaGamma, Christina T
Wang, Huikun
Tsai, Valerie S
Kerspern, Damien
Moritz, Amy E
Sibley, David R
Lutas, Andrew
Moratalla, Rosario
Freyberg, Zachary
Tejeda, Hugo A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Institute of Mental Health (US)
Brain and Behavior Research Foundation
Pittsburgh Foundation
0000-0001-7387-3433
0000-0001-8549-3315
0000-0001-7253-6638
0000-0003-3813-0049
0000-0001-6003-717X
0000-0002-0624-962X
0000-0002-6991-2898
0000-0002-7623-8010
0000-0001-6460-0118
0000-0003-2222-6222
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
topic http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
description Dopamine (DA) release in striatal circuits, including the nucleus accumbens medial shell (mNAcSh), tracks separable features of reward like motivation and reinforcement. However, the cellular and circuit mechanisms by which DA receptors transform DA release into distinct constructs of reward remain unclear. Here we show that DA D3 receptor (D3R) signaling in the mNAcSh drives motivated behavior in mice by regulating local microcircuits. Furthermore, D3Rs coexpress with DA D1 receptors, which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report nonoverlapping physiological actions of D3R and DA D1 receptor signaling in mNAcSh neurons. Our results establish a fundamental framework wherein DA signaling within the same nucleus accumbens cell type is physiologically compartmentalized via actions on distinct DA receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors relevant to the etiology of neuropsychiatric disorders.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/403810
https://api.elsevier.com/content/abstract/scopus_id/85211921464
url http://hdl.handle.net/10261/403810
https://api.elsevier.com/content/abstract/scopus_id/85211921464
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature neuroscience
https://doi.org/10.1038/s41593-024-01819-9
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412850435358720
spelling Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptorsEnriquez-Traba, JuanArenivar, MiguelYarur-Castillo, Hector ENoh, ChloeFlores, Rodolfo JWeil, TenleyRoy, SnehashisUsdin, Ted BLaGamma, Christina TWang, HuikunTsai, Valerie SKerspern, DamienMoritz, Amy ESibley, David RLutas, AndrewMoratalla, RosarioFreyberg, ZacharyTejeda, Hugo Ahttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all agesDopamine (DA) release in striatal circuits, including the nucleus accumbens medial shell (mNAcSh), tracks separable features of reward like motivation and reinforcement. However, the cellular and circuit mechanisms by which DA receptors transform DA release into distinct constructs of reward remain unclear. Here we show that DA D3 receptor (D3R) signaling in the mNAcSh drives motivated behavior in mice by regulating local microcircuits. Furthermore, D3Rs coexpress with DA D1 receptors, which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report nonoverlapping physiological actions of D3R and DA D1 receptor signaling in mNAcSh neurons. Our results establish a fundamental framework wherein DA signaling within the same nucleus accumbens cell type is physiologically compartmentalized via actions on distinct DA receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors relevant to the etiology of neuropsychiatric disorders.This work was supported by the National Institute of Mental Health Intramural Research Program (ZIA MH002970-04) (H.A.T.), a Brain and Behavior Research Foundation NARSAD Young Investigator Award (H.A.T.), NIH Center for Compulsive Behavior Fellowships (R.F.G. and H.E.Y.), Department of Defense PRMRP Investigator-Initiated Award (PR141292) (Z.F.), Department of Defense PRMRP Expansion Award (PR210207) (Z.F.), John F. and Nancy A. Emmerling Fund of The Pittsburgh Foundation (Z.F.), R01DA061243 (Z.F.), R01ES034037 (Z.F.), R01DK124219 (Z.F.), and a NIH Post-Doctoral Research Associate Training Fellowship (R.F.G). The funders had no role in study design, data collection and analysis, decision to publish or preparation´of the manuscript. The authors would like to thank Sarah Williams and Jonathan Kuo of the NIMH Systems Neuroscience Imaging Resource and Dr. Samer Hattar for their microscopy support. The authors also acknowledge Dr. Yogita Chudasama, Alice Graham and members of the NIMH Rodent Behavior Core for behavioral equipment support and Dr. Samer Hattar for sharing running wheels. The authors also thank Drs. Claudia Schmauss, Jonathan Javitch, and Marcelo Rubinstein for the design of the Drd3fl/fl mouse strain as well as Dr. Siu-Pok Yee and the Center for Mouse Genome Modification at UConn Health for the construction of the Drd3fl/fl mice. We additionally acknowledge Dr. Veronica Alvarez and members of the Alvarez laboratory including Drs. Lauren Dobbs and Miriam Bocarsly for all of their invaluable help in making the Drd3fl/fl mice congenic with the C57BL/6J genetic background. We would like to thank members of the Unit on Neuromodulation and Synaptic Integration and Drs. Mario Penzo, Marco Pignatelli, Federica Lucantonio, Eastman Lewis, Detlef Vullhorst, and Andres Buonanno for discussions and critical reading of the manuscript.Peer reviewedNature Publishing GroupNational Institute of Mental Health (US)Brain and Behavior Research FoundationPittsburgh Foundation0000-0001-7387-34330000-0001-8549-33150000-0001-7253-66380000-0003-3813-00490000-0001-6003-717X0000-0002-0624-962X0000-0002-6991-28980000-0002-7623-80100000-0001-6460-01180000-0003-2222-6222Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/403810https://api.elsevier.com/content/abstract/scopus_id/85211921464reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésNature neurosciencehttps://doi.org/10.1038/s41593-024-01819-9Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4038102026-05-22T06:33:51Z
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