MIDBRAIN INPUT REGULATES MOTOR THALAMIC RETICULAR NUCLEUS ACTIVITY DURING SKILLED FORELIMB MOVEMENT

Movement relies on coordinated activity across distributed brain networks that link subcortical structures and cortex. The motor thalamus occupies a central position in these networks, and its activity is shaped by inhibition from the thalamic reticular nucleus (TRN), a GABAergic shell that provides topographically organized input to thalamic nuclei. While communication principles between thalamocortical centers and the TRN have begun to be unraveled, how TRN circuits contribute to motor control remains largely unknown. Here, we leverage circuit tracing strategies in mice to delineate the motor sector of the TRN. Recordings from identified motor TRN neurons during a skilled forelimb task revealed movement-correlated changes in its firing rate. Optogenetic perturbation of this activity disrupts ongoing movement, demonstrating the important role of this circuitry in forelimb control. To identify inputs that might contribute to these movement-specific activity changes, we mapped afferents to the motor TRN. We uncovered a prominent inhibitory midbrain source that provides topographically organized synaptic input selectively to this sector. This midbrain pathway acts as a hub, integrating signals from multiple motor-related regions and positioning it as an integrative node upstream of the motor TRN. Electrophysiological recordings during behavior show that this midbrain–TRN pathway and motor TRN neurons undergo complementary activity changes during forelimb movement, consistent with coordinated circuit dynamics. Our findings offer new insight into the organization and function of synaptic inputs to the TRN and highlight the contribution of a previously uncharacterized inhibitory input to the TRN within the broader thalamocortical network.