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Title: “Pathological Neural Circuit States of the Dorsal Striatum in Parkinson’s Disease”
Committee:
Dr. Xue Han – BME (Advisor, Chair)
Dr. David Boas – BME, ECE
Dr. Michael Economo – BME
Dr. Mark Kramer – Mathematics & Statistics
Abstract:
Parkinson’s disease (PD) affects nearly one million people in the US alone, and its prevalence keeps rising. This debilitating disease is caused by degeneration of dopamine neurons in the substantia nigra pars compacta (SNpc) that project to the dorsal striatum. The dorsal striatum, a major structure of the basal ganglia circuit, guides voluntary movement by coordinating various cortical and sub-cortical brain regions. Over the years, many studies have demonstrated that individual striatal neurons are modulated during movement and their spiking patterns are altered upon dopamine depletion. However, population dynamics among a set of striatal neurons during voluntary movement in healthy and disease conditions are largely unknown. Through recording local field potentials (LFP), a bulk measure of summed neural activities, previous studies found that PD is often accompanied by pathologically exaggerated beta power oscillations (10-30Hz) in all major structures of the basal ganglia circuit, including the dorsal striatum. However, the mechanism by which these oscillations occur and the relationship between LFP and neural activity in the striatum remains largely unknown. This project aims to study how dopamine depletion alters population neural activity in the dorsal striatum. Specifically, I am interested in how the relationship between calcium dynamics of different cell populations, bulk LFP, and movement is altered by dopamine depletion and replacement. At the conclusion of this study we hope to better understand how neural activity in the striatum is altered by dopamine depletion, and how these changes are correlated with the LFP. Such understanding could provide mechanistic insight on how striatal circuit participate movement and contribute to PD, and help the development of more efficient closed loop deep brain stimulation (DBS) treatments for PD.
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