Reference code: | PT/FB/BL-2016-030.03 |
Location: | BF-GMS
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Title:
| Nucleus accumbens microcircuit underlying D2-MSN-driven increase in motivation
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Publication year: | 2018
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URL:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957524/
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Abstract/Results: | ABSTRACT:
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.
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Accessibility: | Document exists in file
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Language:
| eng
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Author:
| Soares-Cunha, C.
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Secondary author(s):
| Coimbra, B., Domingues, A. V., Vasconcelos, N., Sousa, N., Rodrigues, A. J.
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Document type:
| Article
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Number of reproductions:
| 1
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Percentiles:
| 5
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Reference:
| 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, 5(2), e0386-18. https://doi.org/10.1523/ENEURO.0386-18.2018
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2-year Impact Factor: | 3.544|2019
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Impact factor notes: | Impact factor computed since 2019
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Times cited: | 47|2024-02-09
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Indexed document: | Yes
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Quartile: | Q2
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Keywords: | Basal ganglia / Medium spiny neurons / Motivation / Nucleus accumbens / Optogenetics / Reward
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Nucleus accumbens microcircuit underlying D2-MSN-driven increase in motivation |