Dual roles for nucleus accumbens core dopamine D1-expressing neurons projecting to the substantia nigra pars reticulata in limbic and motor control

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-MSNs (NAcD1-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 NAcD1-MSN-SNr pathway may be able to influence both limbic and motor functions. In this study we investigated the effect of optogenetic activation of the NAcD1-MSN-SNr pathway on reward-learning and locomotor behavior. 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. These findings indicate that the NAcD1-MSN-SNr pathway is able to control both reward learning and motor behaviors.