Dual Roles for Nucleus Accumbens Core Dopamine D1-Expressing Neurons Projecting to the Substantia Nigra Pars Reticulata in Limbic and Motor Control in Male Mice

Abstract

The nucleus accumbens (NAc) is a critical component of a limbic basal ganglia circuit that is thought to play an important role in decision-making and the processing of rewarding stimuli. As part of this circuit, dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the NAc core are known to send a major projection to the substantia nigra pars reticulata (SNr). However, the functional role of this SNr-projecting NAc D1-MSN (NAc^D1-MSN-SNr) pathway is still largely uncharacterized. Moreover, as the SNr is thought to belong to both limbic and motor information-processing basal ganglia loops, it is possible that the NAc^D1-MSN-SNr pathway may be able to influence both limbic and motor functions. In this study, we investigated the effect of optogenetic manipulation of the NAc^D1-MSN-SNr pathway on reward-learning and locomotor behavior in male mice. Stimulation of the axon terminals of NAc core D1-MSNs in the SNr induced a preference for a laser-paired location, self-stimulation via a laser-paired lever, and augmented instrumental responding for a liquid reward-paired lever. Additionally, stimulation was observed to increase locomotor behavior when delivered bilaterally and induced contralateral turning behavior when delivered unilaterally. However, interestingly, inhibition of this pathway did not alter either reward-related behaviors or locomotion. These findings indicate that the NAc^D1-MSN-SNr pathway is able to control both reward learning and motor behaviors.

Keywords: basal ganglia; dopamine; motor; nucleus accumbens; reward; substantia nigra.