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 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.

Ongoing experiments examine how perturbing the dopamine system alters reach kinematics by tracking individual digits with deeplabcut, as well as spontaneous dopamine signaling during skill acquisition and performance.

RELEVANT PUBLICATIONS

• Hunter J, Bova A, Stevens A, Leventhal DK. Dopamine neuron stimulation induces context-dependent abnormal involuntary movements in healthy rats. iScience. 2022 Feb 22;25(3):103974. doi: 10.1016/j.isci.2022.103974. PMID: 35281727; PMCID: PMC8914546.

• Bova A, Ferris K, Leventhal DK. Evolution of Gross Forelimb and Fine Digit Kinematics during Skilled Reaching Acquisition in Rats. eNeuro. 2021 Oct 27;8(5):ENEURO.0153-21.2021. doi: 10.1523/ENEURO.0153-21.2021. PMID: 34625461; PMCID: PMC8555885.

• Bova A, Gaidica M, Hurst A, Iwai Y, Hunter J, Leventhal DK. Precisely-timed dopamine signals establish distinct kinematic representations of skilled movements. Elife. 2020; 9 doi:10.7554/eLife.61591. PMID: 33245045; PMCID: PMC7861618

• Bova A, Kernodle K, Mulligan K, Leventhal D. Automated Rat Single-Pellet Reaching with 3-Dimensional Reconstruction of Paw and Digit Trajectories. J Vis Exp. 2019; 149) doi:10.3791/59979. PMID: 31355787. PMCID: PMC7416789

• Albin RL, Leventhal DK. The missing, the short, and the long: Levodopa responses and dopamine actions. Ann Neurol. 2017; doi:10.1002/ana.24961. PMCID: PMC5526730.

• Ellens DJ, Gaidica M, Toader A et al. An automated rat single pellet reaching system with high-speed video capture. Journal of Neuroscience Methods. 2016; 271 119-127. doi:10.1016/j.jneumeth.2016.07.009. PMCID: PMC5003677.