Cerebellar Control of Reach Kinematics for Endpoint Precision

Abstract

The cerebellum is well appreciated to impart speed, smoothness, and precision to skilled movements such as reaching. How these functions are executed by the final output stage of the cerebellum, the cerebellar nuclei, remains unknown. Here, we identify a causal relationship between cerebellar output and mouse reach kinematics and show how that relationship is leveraged endogenously to enhance reach precision. Activity in the anterior interposed nucleus (IntA) was remarkably well aligned to reach endpoint, scaling with the magnitude of limb deceleration. Closed-loop optogenetic modulation of IntA activity, triggered on reach, supported a causal role for this activity in controlling reach velocity in real time. Relating endogenous neural variability to kinematic variability, we found that IntA endpoint activity is adaptively engaged relative to variations in initial reach velocity, supporting endpoint precision. Taken together, these results provide a framework for understanding the physiology and pathophysiology of the intermediate cerebellum during precise skilled movements.

Keywords: cerebellar nuclei; closed-loop optogenetics; dysmetria; forelimb; interposed; kinematics; motor control; motor variability; precision; reaching.