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

• Published in: Neuron (Cambridge, Mass.) Vol. 108; no. 3; pp. 568 - 581.e6
• Main Authors: Vancraeyenest, Pascaline, Arsenault, John T., Li, Xiaolian, Zhu, Qi, Kobayashi, Kenta, Isa, Kaoru, Isa, Tadashi, Vanduffel, Wim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.11.2020; Elsevier Limited
• Subjects: Animals; Cortex (temporal); Cytomegalovirus; Decision making; Dopamine; Dopamine receptors; Experiments; fMRI; functional connectivity; Learning; Learning - physiology; Macaca mulatta; macaque; Mental task performance; Motivation; Motivation - physiology; Neural Pathways - physiology; Nucleus accumbens; Nucleus Accumbens - physiology; pathway-selective reversible inactivation; Reinforcement; Reinforcement, Psychology; Ventral Tegmental Area - physiology; Ventral tegmentum; viral vector; VTA; fMRI; macaque; VTA; functional connectivity; motivation; pathway-selective reversible inactivation; learning; nucleus accumbens; viral vector; dopamine
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2020.07.013

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 increased network-level functional connectivity, especially in fronto-temporal cortex. 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 a motivation-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. [Display omitted] •Reversible inactivation of the VTA-to-NAc pathway was achieved in monkeys•Mesoaccumbal circuit inactivation reduced high-effort motivational behavior•Unexpectedly, this perturbation did not affect reinforcement-based learning•The inactivation increased functional connectivity mainly in fronto-temporal circuits Vancraeyenest et al. reversibly inactivated the pathway from the VTA to the NAc using a double-infection viral vector approach in macaques. This mainly affected dopaminergic projections and resulted in increased functional connectivity, especially pronounced in fronto-temporal circuits. Surprisingly, reinforcement-based learning remained unaffected, contrary to motivational behavior requiring high effort.