The monoamine neurotransmitter serotonin (5-HT) is an essential component of vertebrate cognitive function and the autonomous nervous system, regulating body temperature, sleep, appetite, and mood. Abnormal 5-HT signaling is implicated in a variety of disorders such as depression, anxiety, alcoholism, and obsessive-compulsive disorder. Synaptic serotonergic activity is primarily regulated by the recycling of 5-HT from the synaptic cleft by the presynaptic 5-HT transporter (SERT), a target for many psychostimulants and anti-depressants such as MDMA (Ecstasy) and Fluoxetine (Prozac). In the model system Caenorhabditis elegans (C. elegans), 5-HT is an active participant in a variety of motor, autonomic, and behavioral functions including egg-laying, pharyngeal pumping, locomotion, male mating, aging, and enhanced slowing. The goal of this work is to use the C. elegans model system to manipulate the SERT homolog (MOD-5) and examine regulatory genes controlling MOD-5 trafficking, localization, and activity. We characterized the behavioral phenotypes of endogenous 5-HT activity in C. elegans and in 5-HT transporter deletion mutants, especially those pertaining to locomotor function. We also describe a novel, food dependent immobilization phenotype and use genetic and pharmacological approaches to establish the role of 5-HT and MOD-5 within this phenotype. These techniques provide the necessary tools for use of this phenotype as the basis for a forward genetic screen which will provide unbiased assessments of transporter regulatory molecules. This work provides the foundation for elucidation of proteins that regulate determinants of serotonin transporter function and support normal serotonin transporter activity.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07222010-100913 |
| Date | 17 August 2010 |
| Creators | Ramoz, Leda Lallonie |
| Contributors | Randy D. Blakely, Aurelio Galli |
| 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-07222010-100913/ |
| 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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