Functional heterogeneity within the primate ventral striatum for motivational regulation.

Abstract

The ventral striatum (VS) is a key brain region for reward processing and motivation, and its dysfunctions have been implicated in psychiatric disorders such as apathy and obsessive-compulsive disorder. Although functional heterogeneity within the VS has been well established in rodents, its relevance and mechanisms in primates remain unclear. To address this issue, we performed bilateral pharmacological inactivation of the VS in two male macaque monkeys using muscimol, a GABAA receptor agonist. Precise targeting was achieved through computed tomography and magnetic resonance imaging. Behavioral effects were evaluated using two methods: a goal-directed task with variable rewards and analysis of spontaneous behavior. Our results demonstrated that anterior (a)VS inactivation induced a hypoactivity state that we termed "resting," whereas posterior (p)VS inactivation elicited compulsive-like "checking" behaviors. Notably, neither the aVS nor the pVS inactivation affected reward value or drive processing, thus differentiating aVS and pVS from those involved in incentive motivation, such as the rostromedial caudate and ventral pallidum. Retrograde tracing demonstrated distinct anatomical projection patterns for the aVS and pVS, supporting their functional segregation. Together, the present results suggest the functional heterogeneity of the primate VS along its anterior-posterior axis, with the aVS and pVS participating in distinct motivational control circuits. Our findings may have important implications for understanding the neural mechanisms of psychiatric disorders and for the development of new therapeutic approaches.Significance Statement The ventral striatum (VS) is a core brain region that is involved in motivation and reward-based behaviors. Its dysfunction is implicated in psychiatric disorders such as apathy and obsessive-compulsive disorder. In macaque monkeys, we used imaging-guided pharmacological manipulations to reveal that the anterior and posterior VS subregions have distinct roles in motivation, independent of the incentive or reward drive. Specifically, anterior VS inactivation induced a hypoactive state, whereas posterior VS inactivation elicited compulsive-like behaviors. These findings reveal distinct motivational mechanisms within the primate VS, thus offering valuable insights into the neural basis of psychiatric disorders and identifying promising therapeutic targets.