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TitleNucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
Author(s)Cunha, Carina Isabel Soares
Coimbra, Bárbara Guimarães Salazar
Domingues, Ana Verónica
Vasconcelos, Nivaldo António Portela
Sousa, Nuno
Rodrigues, Ana João
Keywordsbasal ganglia
medium spiny neurons
nucleus accumbens
Issue date2018
PublisherSociety for Neuroscience
CitationSoares-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
Abstract(s)The 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.
DescriptionAccepted manuscript
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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