Dissociable roles of thalamic nuclei in the refinement of reaches to spatial targets

Abstract

Reaches are complex movements that are critical for survival, and encompass the control of different aspects such as direction, speed, and endpoint precision. Complex movements have been postulated to be learned and controlled through distributed motor networks, of which the thalamus is a highly connected node. Still, the role of different thalamic circuits in learning and controlling specific aspects of reaches has not been investigated. We report dissociable roles of two distinct thalamic nuclei - the parafascicular (Pf) and ventroanterior/ventrolateral (VAL) nuclei - in the refinement of spatial target reaches in mice. Using 2-photon calcium imaging in a head-fixed joystick task where mice learned to reach to a target in space, we found that glutamatergic neurons in both areas were most active during reaches early in learning. Reach-related activity in both areas decreased late in learning, as movement direction was refined and reaches increased in accuracy. Furthermore, the population dynamics of Pf, but not VAL, covaried in different subspaces in early and late learning, but eventually stabilized in late learning. The neural activity in Pf, but not VAL, encoded the direction of reaches in early but not late learning. Accordingly, bilateral lesions of Pf before, but not after learning, strongly and specifically impaired the refinement of reach direction. VAL lesions did not impact direction refinement, but instead resulted in increased speed and target overshoot. Our findings provide new evidence that the thalamus is a critical motor node in the learning and control of reaching movements, with specific subnuclei controlling distinct aspects of the reach early in learning.