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

Our recent work (Gaidica et al, J Neurosci, 2018) showed that motor thalamic neurons tend to fire early and transiently during a ballistic movement, with distinct populations of neurons encoding specific aspects of the subsequent movement. Ongoing experiments are aimed at understanding the physiologic and anatomic basis for these coding properties using behavioral, electrophysiological, and optical techniques. Understanding how motor thalamus integrates basal ganglia, cerebellar, and cortical information will be a significant step towards understanding the pathophysiology of Parkinson Disease and related disorders, and likely to improve current treatments (for example, deep brain stimulation).





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