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

ENeuro
Carina Soares-CunhaAna João Rodrigues

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 r...Continue Reading

Citations

Jun 13, 2019·Basic & Clinical Pharmacology & Toxicology·Pedro R OlivettiChristoph Kellendonk
Nov 28, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jonathan M HailwoodTimothy J Bussey
Aug 30, 2019·Molecular Psychiatry·Carina Soares-CunhaAna João Rodrigues
Dec 29, 2019·Scientific Reports·Jaime J CastrellonGregory R Samanez-Larkin
Nov 21, 2020·Psychopharmacology·Jaime J CastrellonGregory R Samanez-Larkin

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Methods Mentioned

BETA
dot blot
confocal microscopy

Software Mentioned

PC
GraphPad Prism
Med
Spike2

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