Selective Mesoaccumbal Pathway Inactivation Affects Motivation But Not Reinforcement-Based Learning in Macaques

Rodent studies have demonstrated the role of the mesoaccumbal circuit in reinforcement-based learning. Importantly, however, while phasic activity of the ventral tegmental area (VTA) contributes to reinforcement learning, rodent evidence suggests that slow changes in tonic VTA activity and associated accumbal dopamine release help regulate motivational behavior. Nonetheless, the consequences of sustained blockage of the mesoaccumbal circuit for motivation and reinforcement learning have not yet been examined in primates. Using a double-infection viral vector technique, we demonstrate that selective, unidirectional and reversible blockage of the primarily dopaminergic mesoaccumbal circuit in monkeys profoundly increased network-level functional connectivity. These global network changes were not associated with deficits in reinforcement learning during an object discrimination reversal task. In contrast, sustained mesoaccumbal inactivation greatly reduced motivation for performing an effort-based decision-making task. Thus, the mesoaccumbal pathway in primates is critical for high-effort motivation, but not for all forms of reinforcement-based learning.