All ETDs from UAB

Advisory Committee Chair

Karen L Gamble

Advisory Committee Members

Rita M Cowell

Alec J Davidson

Lori L McMahon

Linda Overstreet-Wadiche

Lucas D Pozzo-Miller

Document Type

Dissertation

Date of Award

2022

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Circadian rhythms are biological processes that cycle across 24 hours. Driven endogenously by widely expressed and highly conserved clock genes that compose the circadian molecular clock, circadian rhythms are exhibited in numerous facets of physiology across nearly every tissue throughout the body. Diurnal rhythms in cognition, long-term potentiation (LTP), and the expression of clock genes in hippocampus subfields support a role for circadian regulation of hippocampus physiology. However, little is known regarding the circadian molecular clock and diurnal rhythms in neurophysiology at the cellular level. Here, we characterized diurnal differences in spatial memory, LTP, excitability of and synaptic transmission onto CA1 pyramidal neurons, in both male and female mice. We found that both sex and time of day impact spatial memory and synaptic input onto CA1 pyramidal neurons, but only time of day influenced LTP and pyramidal neuron excitability. Additionally, we revealed differential effects on enhanced nighttime CA1 pyramidal neuron excitability that were dependent on position along the anteriorposterior hippocampus axis. Next, we present evidence for the regulation of hippocampus physiology by a cell-autonomous circadian molecular clock in parvalbumin-expressing interneurons. The prevalence of circadian rhythms disruption, interneuron dysfunction, and hippocampus circuit pathology in a number of neurodegenerative diseases, neuropsychiatric, and neurological disorders underscores the value of and need for iv investigation into clock-controlled, cell-type specific neurophysiology in the hippocampus. Indeed, insights gleaned from this dissertation have the potential to aid in the discovery of mechanisms underlying hippocampus-related diseases and could help improve current disease treatment outcomes by informing their appropriate timing. Moreover, our findings might promote future research into preventative approaches that improve human health by leveraging the circadian system.

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