Date of Award

2016

Document Type

Open Access Thesis

Department

Biomedical Science

Sub-Department

School of Medicine

First Advisor

Lawrence Reagan

Abstract

Leptin, a peptide synthesized by adipocytes in the periphery, has been shown to play significant roles in feeding and energy expenditure mediated by the hypothalamus. Growing evidence supports the role of leptin in influencing synaptic plasticity in the hippocampus in that leptin dose-dependently enhances LTP, alters morphology and neurogenesis, facilitates spatial learning and memory, as well as memory retention. Models of leptin deficiency and resistance have further supported the importance of leptin in synaptic plasticity by exhibiting deficits in electrophysiological, morphological and behavioral tests that are improved after leptin restoration. The effects of leptin when applied directly into the hippocampus have clear effects on synaptic plasticity; however, indirect pathways may also be activated by leptin that result in synaptic plasticity changes in the hippocampus. Due to the nature of the release of leptin from the peripheral adipocytes, the interconnectivity of the brain, and the localization of leptin receptors throughout many brain regions, support the hypothesis that leptin could mediate synaptic plasticity changes in the hippocampus through multi-synaptic circuitry in addition to its direct effects. A variety of brain regions that express leptin receptors project both directly and indirectly to the hippocampus, including many nuclei of the hypothalamus, raphe nucleus, locus coeruleus and ventral tegmental area and therefore pose as potential starting points for brain-wide networks that leptin could influence for the regulation of synaptic plasticity in the hippocampus.

Rights

© 2016, Catherine Van Doorn

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