Document Type

Honors Project

Abstract

Parkinson’s disease (PD), a neurodegenerative disorder originating in the dopaminergic cells of the basal ganglia, is characterized by severe motor impairments such as tremors, bradykinesia, and postural instability. However, non-motor symptoms impacting sensory systems and cognition are consistently pointed to as more greatly affecting quality of life for PD patients. Cognitive impairments in PD can include changes in reward processing, depression, apathy, and increases in risk-taking behavior. Additionally, learning and memory deficits are seen in PD, specifically in motor sequence learning. Often, the neural correlates of sequence learning impairments are traced to the substantia nigra. However, there is some evidence in the literature that the ventral tegmental area (VTA) could also play a role in sequence learning deficits. In the present study we investigate the potential role of the VTA in sequence learning using a unilateral 6-OHDA lesion model of PD in mice. In comparison to control animals (n=3), some lesion animals (2 out of n=3) experienced an impairment in performance and rate of learning on a sequence task post-lesion surgery. This impairment also occurred without significant changes in motor skill measured by gait analysis and a cylinder test of forelimb laterality. This indicates that a lesion to the VTA may impact sequence learning without causing motor impairment- pointing to a more direct role of the VTA in sequence learning. This result contributes to our understanding of the neural correlates of cognitive impairments in PD, and could provide a basis for more targeted treatment of PD.

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