Movement-related increases in subthalamic activity optimize locomotion

The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while ontogenetic excitation typically has opposing effects. Subthalamic and motor activity are also inversely correlated in movement disorders. However, most STN neurons exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated treadmill locomotion. The majority of STN neurons (type 1) exhibited locomotion-dependent increases in activity, with half encoding the locomotor cycle. A minority of neurons exhibited dips in activity or were uncorrelated with movement. Brief optogenetic inhibition of the dorsolateral STN (where type 1 neurons are concentrated) slowed and prematurely terminated locomotion. In Q175 Huntington's disease mice abnormally brief, low-velocity locomotion was specifically associated with type 1 hyperactivity. Together these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.