As the population grows and lifespan increases, the need to better understand the normative aging process also increases. Furthermore, with these global changes, the number of people who suffer from diseases of pathological aging such as Parkinson’s disease (PD) will also grow. In-vivo electrophysiology provides a way to look at real-time brain dynamics in order to better understand network alterations in aging and discover biomarkers of disease. The studies described in this thesis are aimed at better understanding electrophysiological changes to memory systems in rodent models of aging and PD. The first study examines how hippocampal low gamma (30-55Hz) and high gamma (65-90Hz), and their relationship to single unit activity and theta (6-9Hz) oscillations, are modulated by age and network instability (remapping) as rats perform a spatial eye-blink conditioning task. Aged animals showed decreased theta frequency compared to young animals, but theta power, gamma power, and theta-gamma coupling did not differ between groups. Overall measures of session theta-phase gamma-amplitude coupling were correlated with the strength of eye-blink conditioning. At the single-unit level, a higher proportion of principal cells in aged animals were phase-locked to high gamma activity than in young animals, and were phase-locked to a greater extent. Finally, on days when rats remapped, a lower proportion of principal cells were locked to high gamma than on stable days. These results suggest a role for high gamma in network stability or age-related compensatory mechanisms. The second study examines how sleep behavior and sleep spindles are altered in a LRRK2-G2019S knock-in mouse model of prodromal genetic PD. G2019S mice showed patterns of fragmented sleep, a common feature of prodromal PD. Additionally, these mice showed altered sleep spindle activity compared to wild-type controls, and spindles in G2019S mice were longer and more frequent than those in controls. These differences may point towards sleep spindles as potential prodromal biomarkers of LRRK2 PD. Together the data presented in this thesis reveal potential electrophysiological signatures of network alterations that may provide insights into the neurobiological mechanisms underlying cognitive deficits associated with normal and pathological aging.
|Advisor:||Cowen, Stephen L.|
|Commitee:||Allen, John J. B., Falk, Torsten|
|School:||The University of Arizona|
|School Location:||United States -- Arizona|
|Source:||DAI-B 81/12(E), Dissertation Abstracts International|
|Keywords:||Aging, Electrophysiology, Gamma, LRRK2, Parkinson's Disease, Sleep Spindles|
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