Acetylcholine demixes heterogeneous dopamine signals for learning and moving

Midbrain dopamine neurons promote both reinforcement learning and movement vigour ^1–12 . A major outstanding question is how dopamine-recipient neurons in the striatum parse these heterogeneous signals. Previous work suggests that cholinergic striatal interneurons may play a role, perhaps by gating dopamine-dependent plasticity ^13–16 , but this has not been tested in behaving animals. Here we studied rats performing a decision-making task with reward- and movement-related events at distinct time points. Optical measurement of dopamine and acetylcholine release in the dorsomedial striatum (DMS) revealed distinct dynamics at task events. Reward cues evoked cholinergic pauses with different phase relationships relative to dopamine. When dopamine slightly lagged cholinergic dips, dopamine predicted future behaviour, and DMS firing rates on subsequent trials. In contrast, when dopamine slightly preceded cholinergic dips, there was no observable relationship between dopamine and learning. Finally, when dopamine was coincident with cholinergic bursts, it preceded and predicted the vigour of upcoming contralateral orienting movements. Our findings suggest that the precise phase relationship between dopamine and acetylcholine allows dopamine to be used for either movement or learning depending on instantaneous behavioural context.