Date of Award

1-1-2014

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Psychology

Program

Behavioral Neuroscience

Content Description

1 online resource (xii, 158 pages) : illustrations (some color)

Dissertation/Thesis Chair

Ewan C McNay

Committee Members

Lauren Jacobson, Andrew M Poulos

Keywords

Contextual fear conditioning, Glucocorticoids, Hippocampus, Hypoglycemia, pCREB, Serum/Glucocorticoid-inducible Kinase-1, Hippocampus (Brain), Memory

Subject Categories

Molecular Biology | Neuroscience and Neurobiology | Psychology

Abstract

Recurrent hypoglycemia (RH) occurs with the over administration of insulin resulting in severe hypoglycemia on a repetitive basis. This occurs most commonly among Type I Diabetics who rely on exogenous insulin replacement for management of their disease; however it is becoming increasingly common among Type II Diabetics. Although cognitive deficits are reported during hypoglycemia, the period following restoration of euglycemia has been denoted by improved hippocampally-mediated short-term and working memory in humans and rodents, respectively. RH is also associated with an altered glucocorticoid secretion profile in response to hypoglycemia. In vitro and in vivo approaches were utilized with the goal to 1) extend previous behavioral work to include a measure of hippocampus-dependent long-term memory, 2) characterize physiological changes occurring at several time points in the dorsal hippocampus in response to RH which may account for improved hippocampal-dependent contextual learning, and 3) determine whether glucocorticoid actions within the dorsal hippocampus were responsible for mediating any of these effects. Hypoglycemia was induced once a day for three consecutive days, with or without an infusion of glucocorticoid/mineralocorticoid receptor antagonists to the dorsal hippocampus. RH consistently produced increased learning in contextual conditioned fear. At time points analyzed, RH also increased glutamate levels, glucocorticoid receptor, SGK1, plasma membrane levels of AMPA receptor, and pCREB, of which SGK1 and AMPA receptors were dependent on glucocorticoids. These results indicate that RH produces several physiological changes in the dorsal hippocampus which are conducive to enhanced hippocampus-dependent contextual learning. Although the addition of glucocorticoid antagonists did not significantly attenuate all changes produced by RH, changes to plasma membrane levels of AMPA receptors and SGK1, proteins which exert significant effects over hippocampal learning and plasticity, support the hypothesis that glucocorticoids are responsible for mediating some effects of RH on the dorsal hippocampus. Additionally, all changes produced by RH indicate an adaptive response within the dorsal hippocampus designed to reduce physiological damage which could arise following repeated exposure to severe hypoglycemia.

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