Acetylcholine demixes heterogeneous dopamine signals for learning and moving.

Midbrain dopamine neurons promote reinforcement learning and movement vigor. A major outstanding question is how dopamine-recipient neurons in the striatum parse these heterogeneous signals. Here we characterized dopamine and acetylcholine release in the dorsomedial striatum (DMS) of rats performing a decision-making task. We found that dopamine acted as a reward prediction error (RPE), modulating behavior and DMS spiking on subsequent trials when coincident with pauses in cholinergic release. In contrast, at task events that elicited coincident bursts of acetylcholine and dopamine, dopamine preceded contralateral movements and predicted movement vigor without inducing plastic changes in DMS firing rates. Our findings provide a circuit-level mechanism by which cholinergic modulation allows the same dopamine signals to be used for either movement or learning depending on instantaneous behavioral context.