In vivo regulation of CNS neurotransmission by trace amines

这一提议将决定哺乳动物大脑中微量胺的正常功能。痕量胺是一组存在于所有物种中的化学物质。虽然它们在昆虫中的作用已经很好地确定了，但它们在哺乳动物中的作用还不清楚。大脑中的神经细胞通过释放被称为神经递质的化学物质来相互交流。这些神经递质是神经细胞对电活动的反应而释放出来的，并与第二个细胞上称为受体的蛋白质结合。对于每种神经递质，都有多种类型的受体可以与之相互作用。神经递质与受体的结合导致信息从一个细胞传递到另一个细胞。微量胺是一组化学物质，与神经递质一样，是在神经细胞中合成的。然而，痕量胺的存在浓度比神经递质低得多，现有证据表明，在通常发现的浓度下，痕量胺不直接在信息从一个细胞传递到另一个细胞的过程中发挥作用。相反，我们之前的数据表明，微量胺可能调节神经递质将信息从一个细胞传递到另一个细胞的效率。目前的工作将通过测量神经递质和示踪胺的各种组合存在下神经细胞的电活动，系统地研究哪些示踪胺通过哪些神经递质调节信号传递的效率。一旦确定了这些相互作用，我们将开始研究这些影响发生的机制。这将通过检查在单个示踪胺受体已被消除的系统中是否可能存在相同的相互作用来完成。通过使用仅与特定神经递质的单个受体相互作用的合成化学物质，我们还将确定观察到的相互作用涉及神经递质受体的哪些亚型。

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.