Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation.
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.
['Soares-Cunha|Carina|C|', 'Coimbra|Bárbara|B|', 'Domingues|Ana Verónica|AV|', 'Vasconcelos|Nivaldo|N|', 'Sousa|Nuno|N|', 'Rodrigues|Ana João|AJ|']
D000818:Animals D001522:Behavior, Animal D008297:Male D009042:Motivation D009474:Neurons D009714:Nucleus Accumbens D062308:Optogenetics D051381:Rats D017208:Rats, Wistar D017448:Receptors, Dopamine D2 D012201:Reward D017557:Ventral Tegmental Area
nucleus accumbens motivation medium spiny neurons optogenetics basal ganglia reward