Spatially heterogeneous acetylcholine dynamics in the striatum promote behavioral flexibility.

ABSTRACT: Being able to switch from established choices to new alternatives when conditions change - behavioral flexibility - is essential for survival. Cholinergic signaling in the striatum contributes to such flexible behavior, yet the timing and spatial organization of acetylcholine release during contingency changes remain unclear, limiting conceptual understanding of its role in behavioral flexibility. Using a genetically encoded acetylcholine sensor and 2-photon imaging in the dorsal striatum of behaving mice, we visualized acetylcholine dynamics during acquisition and reversal learning in a virtual reality Y-maze. Rewarded outcomes evoked phasic decreases in acetylcholine, whereas unexpected non-reward following reversal triggered widespread increases that predicted lose-shift behavior. Targe

SUBMITTER: Sarpong GA 

PROVIDER: S-EPMC12711930 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature