Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation

Bibliographic Details
Main Author: Cunha, Carina Isabel Soares
Publication Date: 2018
Other Authors: Coimbra, Bárbara Guimarães Salazar, Domingues, Ana Verónica, Vasconcelos, Nivaldo António Portela, Sousa, Nuno, Rodrigues, Ana João
Format: Article
Language: eng
Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Download full: http://hdl.handle.net/1822/57950
Summary: Accepted manuscript
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spelling Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivationbasal gangliamedium spiny neuronsmotivationnucleus accumbensoptogeneticsrewardCiências Médicas::Medicina BásicaScience & TechnologyAccepted manuscriptThe nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement. To answer this question, in this work we combined optogenetic modulation of D2-MSNs with in loco pharmacological delivery of specific neurotransmitter antagonists in rats. First, we showed that optogenetic activation of D2-MSNs increases motivation in a progressive ratio (PR) task. We demonstrated that this behavioral effect relies on cholinergic-dependent modulation of dopaminergic signalling of ventral tegmental area (VTA) terminals, which requires D1R and D2R signalling in the NAc. D2-MSN optogenetic activation decreased ventral pallidum (VP) activity, reducing the inhibitory tone to VTA, leading to increased dopaminergic activity. Importantly, optogenetic activation of D2-MSN terminals in the VP was sufficient to recapitulate the motivation enhancement. In summary, our data suggests that optogenetic stimulation of NAc D2-MSNs indirectly modulates VTA dopaminergic activity, contributing for increased motivation. Moreover, both types of dopamine receptors signalling in the NAc are required in order to produce the positive behavioral effects.This work was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Part of the work was supported by the Janssen Neuroscience Prize (1st edition) and by a BIAL Grant (30/2016). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038 and of project POCI-01-0145-FEDER-016428info:eu-repo/semantics/publishedVersionSociety for NeuroscienceUniversidade do MinhoCunha, Carina Isabel SoaresCoimbra, Bárbara Guimarães SalazarDomingues, Ana VerónicaVasconcelos, Nivaldo António PortelaSousa, NunoRodrigues, Ana João20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/57950engSoares-Cunha, C., Coimbra, B., Domingues, A. V., Vasconcelos, N., Sousa, N., & Rodrigues, A. J. (2018). Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation. eNeuro, ENEURO-03862373-28222373-282210.1523/ENEURO.0386-18.201829780881http://www.eneuro.org/content/early/2018/04/19/ENEURO.0386-18.2018info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:31:16Zoai:repositorium.sdum.uminho.pt:1822/57950Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:26:29.945137Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
title Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
spellingShingle Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
Cunha, Carina Isabel Soares
basal ganglia
medium spiny neurons
motivation
nucleus accumbens
optogenetics
reward
Ciências Médicas::Medicina Básica
Science & Technology
title_short Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
title_full Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
title_fullStr Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
title_full_unstemmed Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
title_sort Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
author Cunha, Carina Isabel Soares
author_facet Cunha, Carina Isabel Soares
Coimbra, Bárbara Guimarães Salazar
Domingues, Ana Verónica
Vasconcelos, Nivaldo António Portela
Sousa, Nuno
Rodrigues, Ana João
author_role author
author2 Coimbra, Bárbara Guimarães Salazar
Domingues, Ana Verónica
Vasconcelos, Nivaldo António Portela
Sousa, Nuno
Rodrigues, Ana João
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Cunha, Carina Isabel Soares
Coimbra, Bárbara Guimarães Salazar
Domingues, Ana Verónica
Vasconcelos, Nivaldo António Portela
Sousa, Nuno
Rodrigues, Ana João
dc.subject.por.fl_str_mv basal ganglia
medium spiny neurons
motivation
nucleus accumbens
optogenetics
reward
Ciências Médicas::Medicina Básica
Science & Technology
topic basal ganglia
medium spiny neurons
motivation
nucleus accumbens
optogenetics
reward
Ciências Médicas::Medicina Básica
Science & Technology
description Accepted manuscript
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/57950
url http://hdl.handle.net/1822/57950
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Soares-Cunha, C., Coimbra, B., Domingues, A. V., Vasconcelos, N., Sousa, N., & Rodrigues, A. J. (2018). Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation. eNeuro, ENEURO-0386
2373-2822
2373-2822
10.1523/ENEURO.0386-18.2018
29780881
http://www.eneuro.org/content/early/2018/04/19/ENEURO.0386-18.2018
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799132753447354368

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