Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation

Title: Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation

Journal: eNeuro. 2018 May 16;5(2)

Link: http://dx.doi.org/10.1523/ENEURO.0386-18.2018

Comments:

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.

In this study, authors combined optogenetic modulation of D2-MSNs with in loco pharmacological delivery of specific neurotransmitter antagonists in rats. First, they showed that optogenetic activation of D2-MSNs increases motivation in a progressive ratio (PR) task. They 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.

This study reveals for the first time how D2-MSN stimulation can modulate downstream regions and local microcircuit to increase motivation.

NAc D2-MSN optogenetic activation enhances motivation through enhanced VTA- driven dopaminergic signaling. The behavioral effect was dependent on both D1R and D2R signaling in the NAc, suggesting that a coordinated action between these two striatal populations is needed to increase motivational levels.