Cerebellar modulation of the basal ganglia

Abstract

Fine motor control requires that the structures of the brain coordinate their activity at rapid timescales. Fast communication between the thalamus, motor cortex, cerebellum, and basal ganglia is therefore critical for well-timed and well-executed movements. All of these structures have well-described, robust and short latency communication with one another--except for one pair. The cerebellum and the basal ganglia both compute the fine details of movement, but are thought to compute different aspects of movement. In particular, the cerebellum is thought to coordinate muscle activity while the basal ganglia select the appropriate patterns of activity to engage in. Interestingly, there has been little evidence to suggest that there are direct avenues of functional communication between the cerebellum and basal ganglia. This lack of evidence has led some to suggest that computations and functions of the cerebellum and basal ganglia are completely separate.;However, several mouse models of dystonia have purely cerebellar etiologies. Dystonia is typically a basal ganglia condition, and was elicited by generating aberrant activity within the cerebellum. Moreover, an anatomical disynaptic pathway links the cerebellum to the basal ganglia through the intralaminar nuclei of the thalamus. Thus, it is plausible that aberrant information could be transferred from the cerebellum to the basal ganglia to cause motor disorders. In normal conditions, cerebellar input to the basal ganglia might be used to aid in the execution of well-controlled movements. Thus, the cerebellum might be able to influence the activity of the basal ganglia, although the substrates and properties of this pathway were unknown.;The primary goal of this thesis is to uncover the functional connectivity linking the cerebellum to the basal ganglia. We find that stimulation of the cerebellum yields numerous and robust short latency responses in the basal ganglia, and that these responses are mediated by a disynaptic connection through the thalamus. This connection is also able to modulate the primary input to the basal ganglia--the corticostriatal pathway--by altering long-term plasticity at that site. Given this, I propose that the functions of the cerebellum and basal ganglia are more intertwined than previously thought.