Dynamic control of visually guided locomotion through corticosubthalamic projections.

Goal-directed locomotion requires control signals that propagate from higher order areas to regulate spinal mechanisms. The corticosubthalamic hyperdirect pathway offers a short route for cortical information to reach locomotor centers in the brainstem. We developed a task in which head-fixed mice run to a visual landmark and then stop and wait to collect the reward and examined the role of secondary motor cortex (M2) projections to the subthalamic nucleus (STN) in controlling locomotion. Our behavioral modeling, calcium imaging, and optogenetics manipulation results suggest that the M2-STN pathway can be recruited during visually guided locomotion to rapidly and precisely control the pedunculopontine nucleus (PPN) of the mesencephalic locomotor region through the basal ganglia. By capturing the physiological dynamics through a feedback control model and analyzing neuronal signals in M2, PPN, and STN, we find that the corticosubthalamic projections potentially control PPN activity by differentiating an M2 error signal to ensure fast input-output dynamics.