Movement refinement and cholinergic regulation of outcome-dependent updating during skilled reaching.

Abstract

Motor skill learning transforms initially variable actions into precise and reproducible movements, yet conventional measures of task success can obscure the distinct processes through which this refinement occurs. We combined detailed outcome scoring and kinematic analysis of single-pellet reaching in mice to resolve how individual components of the action change with practice. Decomposing reaching into successive stages revealed improvements in targeting and retrieval, while grasp success after pellet contact did not change detectably. Paw trajectories became more consistent across both successful and unsuccessful reaches, whereas changes in the mean speed profile were detected in successful reaches. To examine how striatal cholinergic signaling contributes to movement refinement and the influence of recent outcomes on subsequent actions, we monitored acetylcholine (ACh) in vivo and inhibited cholinergic interneurons (CINs) during training. ACh was elevated before reach onset and declined during execution across all reach outcomes, with no detectable change between early and late training. CIN inhibition had little effect on movement refinement across days, but altered how recent outcomes influenced the next reach, most clearly following attempts in which the pellet was grasped and then lost. These findings distinguish refinement of the practiced movement from outcome-dependent adjustments to its execution. Together, they raise the possibility that the pre-reach ACh elevation plays a role in enabling the evaluation of recent outcomes to update the execution of the next reach.