Advisory Committee Chair
Advisory Committee Members
Lori L McMahon
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Medicine
Circadian rhythms are ~24-hour cycles in biological processes that are endogenously generated, entrained to light, and synchronized by the suprachiasmatic nucleus of the hypothalamus. One process that is influenced by circadian rhythms is cognitive function, which varies over the course of the day and is likely influenced by changes in neuronal physiology over the course of the day. Dysfunction in circadian rhythms has been documented in many diseases, including Alzheimer’s disease (AD). AD is a neurodegenerative disease most notably characterized by dementia, amyloid beta plaques, and tau tangles. There is currently no cure for AD, and treatments only slow disease progression. Evidence for circadian rhythm dysfunction in AD includes sundowning, a worsening of dementia in the evenings, and altered rest-activity patterns. The hippocampus is a brain region crucial for learning and memory, and this region undergoes severe damage in patients with Alzheimer’s disease. There has been little work done to investigate day-night differences in hippocampal neurophysiology and how it is impacted in AD. Here, we examined day-night differences in hippocampal neurophysiology in and found diurnal regulation of both inhibition and excitation onto CA1 pyramidal cells. We also found differences in excitability of CA1 pyramidal cells, and most notably, uncovered that the directionality of diurnal regulation depends on position in the hippocampus and sex. We discovered that diurnal regulation of inhibition onto and excitation of hippocampal CA1 pyramidal cells is altered, and spatial working iv memory is impaired in mouse models of AD. Together, these data provide new insight into the influence of circadian regulation of hippocampal neurophysiology and emphasize the importance of tailoring studies and treatment interventions to time of day.
Fusilier, Allison R., "Diurnal Variation in Hippocampal Neurophysiology and Pathophysiology" (2021). All ETDs from UAB. 554.