Working memory-based and -free reward prediction in a dual dopamine system in the basal ganglia

Animals optimize their actions by predicting and verifying their outcomes (e.g., rewards). Reward prediction often requires working memory (WM)-based information. To elucidate the neural basis of WM-based reward prediction, we compared the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) in an alternate reward condition (WM-based) with that in a random (WM-free) reward condition in rats and mice. Positron emission tomography revealed greater VTA activation in the WM-based than the WM-free condition. Lateral and medial VTA neurons displayed differential electrophysiological spike activities reflecting WM- based and WM-free reward prediction error, respectively. Furthermore, phasic DA release in the dorsal and ventral striatum changed as WM-based and WM-free classical conditioning progressed. Consistent with our WM-based model, reward acquisition caused a DA dip only in the dorsal striatum. Thus a dual DA system processes WM-based and WM-free reward prediction in parallel. ### Competing Interest Statement The authors have declared no competing interest.