RT Journal Article
SR Electronic
T1 Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0386-18.2018
DO 10.1523/ENEURO.0386-18.2018
A1 Carina Soares-Cunha
A1 Bárbara Coimbra
A1 Ana Verónica Domingues
A1 Nivaldo Vasconcelos
A1 Nuno Sousa
A1 Ana João Rodrigues
YR 2018
UL http://www.eneuro.org/content/early/2018/04/19/ENEURO.0386-18.2018.abstract
AB 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 task. We demonstrated that this behavioural 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 behavioural effects.Significance Statement The nucleus accumbens (NAc) is a key brain region of the reward system and is crucial for motivation. We showed that activation of NAc D2-expressing neurons enhances motivation by modulating VTA dopaminergic activity via ventral pallidum inhibition. The behavioural effect was dependent on local cholinergic-dependent dopamine release by VTA terminals that required D1 and D2 dopamine receptors in the NAc.