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Title page for ETD etd-07222010-100913


Type of Document Master's Thesis
Author Ramoz, Leda Lallonie
URN etd-07222010-100913
Title Food-dependent swimming-induced paralysis in C. elegans: a novel serotonin transporter dependent phenotype
Degree Master of Science
Department Interdisciplinary Studies: Molecular Neuropharmacology
Advisory Committee
Advisor Name Title
Aurelio Galli Committee Chair
Randy D. Blakely Committee Member
Keywords
  • feeding
  • mod-5
  • C. elegans
  • antidepressant
  • serotonin
  • transporter
Date of Defense 2010-07-12
Availability unrestricted
Abstract
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.
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