Projects

The role of dopamine in motor skill acquisition and performance. Parkinson Disease (PD) is characterized by bradykinesia (slowness of movement), rigidity (resistance to passive movement), tremors, and (late in its course) postural instability. Many of these symptoms are directly attributable to the degeneration of midbrain dopaminergic neurons, and improve with dopamine replacement therapy (most notably levodopa). It is not clear, however, why dopamine is important to motor function at a neural systems level.

     Recent data suggest that dopamine is not only important for executing vigorous, accurate movements, but also for acquiring motor skills. The goal of these experiments is to understand the relative contributions of “learning” and “performance” roles of dopamine to the pathogenesis of Parkinson Disease. 

       To test these hypotheses, we have developed an automated “skilled reaching” chamber that combines 3-dimensional motion tracking, electrophysiology, and optogenetics. This allows us to synchronize our electrophysiological and optogenetic apparatus with fine motor behavior on a millisecond time scale.



“Motor” thalamic physiology. “Standard” models of basal ganglia (BG) circuits suggest that GABAergic output tonically suppresses activity in the motor thalamus. When an action is to be performed, BG output pauses, releasing the “motor” thalamus to activate motor cortex. In fact, these circuits are much more complex, but a satisfactory replacement for the “standard” model remains elusive. These experiments are focused on understanding the relationships between BG output, thalamic firing patterns, and network-level activity in cortical-BG-thalamocortical circuits.




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