The Role of Cerebellar Unipolar Brush Cells in Motor Coordination and Motor Learning

The cerebellum predicts and corrects motor outputs based on sensory feedback for smoother and more precise movements, thus contributing to motor coordination and motor learning. One area of the cerebellum, the vestibulocerebellum, integrates vestibular and visual information to regulate balance, gaze stability, and spatial orientation. Highly concentrated within the granule cell layer of this region is a class of excitatory glutamatergic interneurons known as unipolar brush cells (UBCs) that receive input from mossy fibers and synapse onto multiple granule cells and other UBCs. They can be divided into ON and OFF subtypes based on their responses to synaptic stimulation. Prior research has implicated ON UBCs in motor dysfunction, but their role in motor coordination, balance, and motor learning is unclear. To test the hypothesis that ON UBCs contribute to motor coordination and balance, a transgenic mouse line (GRP-Cre) was used to express the GqDREADD (Gq designer receptors exclusively activated by designer drugs) hM3Dq in a subset of ON UBCs in the cerebellum to disrupt their electrical activity. In a second set of experiments, a Cre-dependent caspase 3 AAV (adeno-associated virus) viral vector was injected into the nodulus of the vestibulocerebellum of GRP-Cre mice to selectively ablate a subset of ON UBCs in the region and test whether they were necessary for motor learning. Motor coordination and balance were assessed using the rotor-rod and balance beam in young mice, and the forced swim test was used to assess vestibular function in older mice. Activity levels, anxiety, gross locomotion, and exploration in young mice were assessed using the open field. The results show that neither motor coordination and balance, nor motor learning, were impaired when the ON UBCs were disrupted or ablated in young mice. However, disruptions affected climbing behavior in older mice during the forced swim test, suggesting an age-dependent effect of ON UBCs on vestibular function.