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Acetylcholine demixes heterogeneous dopamine signals for learning and moving

2026/03/25 by Hee Jae Jang, Royall McMahon Ward, Carla E. M. Golden +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Neural dynamics and brain function #Neurotransmitter Receptor Influence on Behavior #Zebrafish Biomedical Research Applications

paper · pdf · doi:10.1038/s41593-026-02227-x

openalex publication_date 2026/03/25 · openalex created_date 2026/03/26 · openalex updated_date 2026/07/31

Abstract

Midbrain dopamine neurons promote reinforcement learning and movement vigor. An outstanding question is how dopamine-recipient neurons in the striatum parse these heterogeneous signals. Previous work suggests that cholinergic striatal interneurons may gate dopamine-dependent plasticity, but this has not been tested in behaving animals. Here we studied rats performing a decision-making task with reward-related and movement-related events. Optical measurement of dopamine and acetylcholine release in the dorsomedial striatum (DMS) revealed that reward cues evoked cholinergic pauses with different phase relationships relative to dopamine. When dopamine lagged cholinergic dips, dopamine predicted future behavior and DMS firing rates on subsequent trials. In contrast, when dopamine 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 vigor of contralateral orienting movements. Our findings suggest that cholinergic dynamics determine whether dopamine promotes vigor or learning, depending on the instantaneous behavioral context. Jang et al. measured dopamine and acetylcholine release in the striatum of rats performing a decision-making task and found that the relative timing of cholinergic and dopamine release gates whether dopamine promotes reinforcement learning or movement vigor.

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