Respective roles of the distinct populations of Medium Spiny Neurons of the Nucleus Accumbens in reward processing

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Walle, Roman | Ducrocq, Fabien | Petitbon, Anna | Fois, G. | Contini, Andrea | Oummadi, Asma | de Smedt-Peyrusse, Véronique | Georges, F. | Trifilieff, Pierre

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National audience. The nucleus accumbens (NAc) is a major structure that plays a key role in action selection and execution as well as reward processing and reward-dependent learning. It is largely composed of GABAergic Medium Spiny Neurons (MSN) that are divided into two distinct subpopulations, those expressing the dopamine D1 receptor (D1R; dMSNs), and those expressing the D2 receptor (D2R; iMSNs). Based on the model of the dorsal striatum, it has been proposed that dMSNs and iMSNs of the NAc play antagonistic effects on reward processing, but their respective roles are still largely debated (Carvalho Poyraz et al. 2016; Soares-Cunha et al. 2016). Herein, we aimed at deeper exploring the implication of these two populations of MSNs of the NAc core on various components of reward processing. Using operant conditioning tasks and pharmacogenetic approaches we show that activation of iMSNs decreases motivation to obtain a food reward but increases food consumption, while inhibition had the opposite effect, with no impact on hedonic reactivity. Interestingly, in vivo electrophysiology experiments in anesthetized animals revealed that the increased iMSN excitability boosts the activity of dopaminergic VTA neurons. Surprisingly, we observed that both inhibition and activation of dMSNs led to a decrease in performance in motivational tasks, likely related to a strong modulation of consummatory processes. Our data shed light on the complex function of dMSNs and iMSNs of the NAc core in reward processing and highlight differential effects on consummatory vs. motivational processes.

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