Vascular conditions alter hippocampal neurophysiology and cortico-hippocampal communication

Abstract

Vascular conditions such as stroke and diabetes are leading causes of disability worldwide. The incidence of these conditions increases dramatically with age, and as the global population increases, the prevalence of these conditions will continue to grow. Recently, a growing body of research has revealed a causal connection between vascular diseases and central nervous system injury, resulting in cognitive deficits and significantly increased risk for neurological conditions, such as dementia and depression. These conditions often increase the risk of further cognitive impairment, quickly accelerating debility and cognitive decline. These conditions have complex interactions with the neurophysiology underlying cognition. Electrophysiology is a powerful tool to understand the neural activity underlying cognitive function. In this work, I use extracellular field potentials recorded in rodent animal models to investigate two disease states associated with central nervous system vascular injury, type 2 diabetes mellitus (T2DM) and chronic ischemic stroke, to better understand how these conditions affect neurophysiological function leading to mild cognitive impairment. In the first chapter, I will cover the necessary background information on T2DM, chronic ischemic stroke, and electrophysiology methods. In the second chapter, I present my findings on the interactions between age and T2DM in the neural activity of the hippocampus using a homozygous db/db mouse model, which is a genetic line that has a defective leptin receptor, a protein that regulates appetite and satiation. In the third chapter, I present my findings on how chronic stroke and a type of therapy called environmental enrichment which has been shown to improve behavioral outcomes interact in a rat model of stroke using distal middle cerebral artery occlusion. Finally, in the fourth chapter, I bring the results of both studies together to see what the broader implications are, and what future directions of this work may look like.