THE SUBTHALAMIC NUCLEUS IN THE REGULATION OF MOTOR VARIABILITY

Motor skills underlie much of what we do, from tying shoes to serving a volleyball. A hallmark of skills is a transition over learning, from variable behavior to precise and stereotyped movements. This change in motor variability must be flexibly, but tightly, regulated: while necessary to explore the motor space to find rewarded solutions, it impairs peak performance. However, how variability regulation is implemented in the mammalian brain remains unclear. The basal ganglia have been implicated, and a transition from dorsomedial striatum (DMS), mediating variable behavior, to dorsolateral striatum (DLS), driving stereotyped movement patterns, correlates with the variability decrease during learning. We suggest a novel mechanism which contributes to regulation of the DMS-DLS transition and thereby variability during skill learning and execution. The subthalamic nucleus (STN), an indirect pathway node, sends largely unexplored feedback connections to striatum: directly to DLS and indirectly to DMS via the anterior thalamic nuclei (ATN). STN receives broad cortical and subcortical input, allowing an integration of striatal signals with internal and external state information. Based on this, STN may modulate the DMS-DLS transition, thereby dynamically regulating motor variability. Indeed, chronic silencing of the STN-DLS projection completely prevents, while silencing of the STN-ATN or ATN-DMS projections promotes development of stereotypy and skill learning. Consistent with a DMS-DLS shift, STN-ATN silencing in experts has no effect, while STN-DLS silencing disrupts stereotypy. Our results suggest novel roles for STN in regulating motor variability, likely by modulating DMS-DLS interplay, as well as unappreciated complexity in the basal ganglia circuitry.