Functions of Trace Amines in the Drosophila Melanogaster Central Nervous System

The trace amines tyramine, octopamine, and -phenylethylamine are found in the nervous systems of animals ranging in complexity from nematodes to mammals. Though their presence in the vertebrate brain is well-documented, trace amines have often been overlooked as metabolic by-products with insignificant physiological relevance. In invertebrates such as Drosophila melanogaster, however, the trace amine octopamine is a well-established neurotransmitter and neuromodulator, and there is increasing evidence that tyramine may function as an independent neuromodulator as well. In this study, I use the fruit fly Drosophila melanogaster as a model system to identify and refine neural roles for the trace amines tyramine and octopamine. I describe the cloning and characterization of two tyrosine decarboxylase (TDC) genes that are essential for the synthesis of these trace amines and demonstrate the molecular and behavioral consequences of aberrant tyramine/octopamine signaling in the fruit fly central nervous system. Additionally, I describe an improved method for the detection of tyramine and octopamine in the Drosophila brain and explain the broad applications this technique may have for the trace amine field. The characterization of the TDC genes and the development of an analytical method by which to measure levels of tyramine and octopamine in the Drosophila brain have the potential to provide valuable information regarding the neural role of trace amines. At the same time, molecular and behavioral analyses of flies with aberrant trace amine signaling may lead to the identification of neural adaptations underlying cocaine responsiveness and sensitization in Drosophila and in higher vertebrates. This work was completed under the advisement of Jay Hirsh, PhD, in the Department of Biology.

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