Cerebellar outputs for rapid directional refinement of forelimb movement

Thanawalla, A. R.; Wilcox, O.; Rhee, E.; Jiang, J.; Huang, K. W.; Yusufi, R.; Saklaway, D.; Nagamori, A.; Conner, J. M.; Chen, A. I.; Azim, E.

doi:10.1101/2025.10.01.679895

bioRxiv · 10.1101/2025.10.01.679895

Cerebellar outputs for rapid directional refinement of forelimb movement

Thanawalla, A. R.·Wilcox, O.·Rhee, E.·Jiang, J.·Huang, K. W.·Yusufi, R.·Saklaway, D.·Nagamori, A.·Conner, J. M.·Chen, A. I.·Azim, E.

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Abstract

Much of our interaction with the world relies on the ability to move our limbs with speed and precision. The cerebellum is critical for movement coordination, yet how outputs from the cerebellum continually guide the limb and whether discrete pathways differentially contribute to adjusting motor output remain unclear. Using intersectional viral approaches in mice, we identify two spatially intermingled yet anatomically distinct cerebellar populations that drive the forelimb either toward or away from the body. Neural recordings reveal cerebellar activity that correlates with and precedes these opposing directional changes in limb movement. Both cerebellar output pathways influence motor neuron and muscle activity within milliseconds, producing reliable effects on limb trajectory despite substantial underlying variability in muscle recruitment patterns. Our findings disentangle a subtype organization to cerebellar limb control, revealing a subcortical circuit basis for online directional refinement during movement execution.

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Thanawalla, A. R., Wilcox, O., Rhee, E., Jiang, J., Huang, K. W., Yusufi, R., Saklaway, D., Nagamori, A., Conner, J. M., Chen, A. I., Azim, E.. 2025-10-02. Cerebellar outputs for rapid directional refinement of forelimb movement. https://doi.org/10.1101/2025.10.01.679895

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