2018/03/01 by Carina Soares‐Cunha, Bárbara Coimbra, Ana Verónica Domingues +3 · 1 citation
Neuroscience · Biochemistry, Genetics and Molecular Biology · Chemistry · Psychology · #Neurotransmitter Receptor Influence on Behavior #Receptor Mechanisms and Signaling #Memory and Neural Mechanisms #Optogenetics #Ventral tegmental area #Nucleus accumbens #Dopaminergic #Neuroscience #Dopamine #Dopamine receptor D2 #Medium spiny neuron #Dopaminergic pathways #Chemistry #Psychology #Striatum
paper · pdf · doi:10.1523/eneuro.0386-18.2018
openalex publication_date 2018/03/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
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.