All ETDs from UAB

Advisory Committee Chair

David Sweatt

Advisory Committee Members

Mary Boggiano

David Knight

Scott Phillips

Diane Tucker

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Knowledge of the molecular mechanisms that underlie learning and memory has advanced a great deal. Research into the role of epigenetics, or modifications above the genome, has the promise of providing an even greater understanding of the precise mechanisms involved in memory formation. Studies of epigenetic regulation of memory in the rodent hippocampus have primarily focused on associative learning using contextual fear conditioning. While these studies have provided valuable insight into the role that epigenetics plays in cognition, it remains to be seen whether the findings generalize to other forms of hippocampus-dependent learning. This work examines the role of epigenetic mechanisms, specifically DNA methylation, in spatial learning using the Morris water maze (MWM), as well as the role of MeCP2, a protein that binds methylated DNA and regulates transcriptional activity, during memory consolidation following contextual fear conditioning. Results revealed an absence of expected spatial learning-induced changes in gene transcript levels or epigenetic modifiers. Exposure to the MWM independent of spatial learning, however, was associated with decreased Bdnf transcript levels and increased H3 acetylation. No changes were found in MeCP2 transcript levels, protein levels, or post-translational modifications in association with contextual fear learning. A possible explanation for the paucity of genome-wide changes is that epigenetic regulation is likely to be highly gene-specific. These results highlight the limitations of these models and studies, and they suggest that epigenetic regulation may be highly localized at the cellular and genomic level. Fully elucidating the role of these epigenetic modifications in hippocampus-dependent learning will further enhance our understanding of the molecular mechanisms of cognition.

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