In vivo regulation of CNS neurotransmission by trace amines

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This proposal will determine the normal function of trace amines in the mammalian brain. Trace amines are a group of chemicals found in all species. Although their role in insects has been well established, their role in mammals is not known. Nerve cells in the brain communicate with each other through the release of chemicals known as neurotransmitters. These neurotransmitters are released from nerve cells in response to electrical activity, and bind to proteins known as receptors on a second cell. For each neurotransmitter there are multiple types of receptors that it can interact with. This binding of neurotransmitter to receptor results in the transmittance of information from one cell to another. The trace amines are a group of chemicals which, like neurotransmitters, are synthesized in nerve cells. However, the trace amines are present in much lower concentrations than neurotransmitters, and available evidence suggests that at the concentrations normally found, trace amines do not function directly in the transmission of information from one cell to the other. Rather, our previous data suggests that trace amines may regulate the efficiency by which neurotransmitters can convey information from one cell to another. The current work will systematically examine which trace amines regulate the efficiency of signaling by which neurotransmitters, by measuring the electrical activity of nerve cells in the presence of various combinations of neurotransmitters and trace amines. Once these interactions have been determined, we will begin to examine the mechanisms by which such effects occur. This will be done by examining whether the same interactions are possible in systems where individual trace amine receptors have been eliminated. By using synthetic chemicals that only interact with individual receptors for a particular neurotransmitter we will also determine which sub-types of neurotransmitter receptor are involved in the observed interactions.