The role of cerebellar output in the control of motor coordination

Project Summary Individuals with damage to the cerebellum exhibit debilitating deficits in motor coordination, characterized by oscillatory movements around an endpoint. The anterior interposed nucleus (IntA) is one of the main output structures from the cerebellum, with inactivation of IntA resulting in dysmetria and an instability of reaching movements. Recent findings from the lab have revealed the role of IntA as a controller of reach endpoints, facilitating precise limb movements through adaptive scaling of firing rate. While considerable progress has been made in understanding the role of the cerebellum in motor control, many questions remain concerning the signals encoded within IntA neurons during limb movement and how they contribute to the production of coordinated movements. Investigating the firing rate code of IntA neurons during complex motor tasks will help to elucidate the role of the cerebellum in anticipatory control and motor learning. To address this gap in knowledge, this proposal utilizes novel behavioral paradigms for skilled reaching in mice, cell type specific in vivo recordings during behavior, and causal optogenetic manipulations of cerebellar output. I will first determine how IntA activity is modulated to ensure endpoint precision to different targets. To do so, I will examine IntA neural dynamics, both in magnitude and timing, and their relationship to key kinematic parameters of reach precision. Secondly, I will test whether the anticipatory control signals of IntA can adapt to account for reach perturbations. Spanning circuit and behavioral levels, this proposal aims to understand the role of cerebellar output in anticipatory motor control for coordinated movement.