Neuroscience
Dissertation under the direction of Professor Randy D. Blakely
This dissertation is focused on the function and regulation of the choline transporter (CHT). I used CHT heterozygous and homozygous mice, and combined biochemical, pharmacological, and behavioral approaches to test the hypothesis that CHT is essential for acetylcholine (ACh) turnover and behaviors dependent on cholinergic signaling in vivo. My work demonstrates that CHT homozygous knockout mice are born with wild type levels of ACh, but are unable to sustain ACh synthesis and release under high demand for ACh turnover. CHT heterozygosity, on the other hand, results in diminished pools of ACh. Consequenly, focused behavioral and pharmacological challenges reveal that CHT heterozygous mice are vulnerable to sustained demands on cholinergically-supported behaviors. In summary, my thesis work provides new insights into the role of CHT in the maintenance of ACh turnover and cholinergic neurotransmission. The CHT heterozygous mice constitute a new animal model of cholinergic dysfunction, and offer opportunities for further studies of CHT function and regulation, with the eventual goal of manipulating CHT in disorders of cholinergic origin.
Approved: Professor Randy D. Blakely, May 2008
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04142008-011434 |
| Date | 15 April 2008 |
| Creators | Bazalakova, Mihaela Hristova |
| Contributors | Michael P. McDonald, P. Jeffrey Conn, David Robertson, Randy D. Blakely |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-04142008-011434/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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