Monkey electrophysiology [1, 2] suggests that the activity of the ventral tegmental area (VIA) helps regulate reinforcement learning and motivated behavior, in part by broadcasting prediction error signals throughout the reward system. However, electrophysiological studies do not allow causal inferences regarding the activity of VIA neurons with respect to these processes because they require artificial manipulation of neuronal firing. Rodent studies fulfilled this requirement by demonstrating that electrical and optogenetic VIA stimulation can induce learning and modulate downstream structures [3-7]. Still, the primate dopamine system has diverged significantly from that of rodents, exhibiting greatly expanded and uniquely distributed cortical and subcortical innervation patterns [8]. Here, we bridge the gap between rodent perturbation studies and monkey electrophysiology using chronic electrical microstimulation of macaque VIA (VIA-EM). VIA-EM was found to reinforce cue selection in an operant task and to motivate future cue selection using a Pavlovian paradigm. Moreover, by combining VIA-EM with concurrent fMRI, we demonstrated that VIA-EM increased fMRI activity throughout most of the dopaminergic reward system. These results establish a causative role for primate VIA in regulating stimulus-specific reinforcement and motivation as well as in modulating activity throughout the reward system.
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