Effects of invertebrate neuropeptides and biogenic amines on synapses and behavior

神经细胞通过释放化学信号来相互交流，这些化学信号会改变目标细胞的电活动。这些化学信号大多数是“多肽”（氨基酸短链），有些是“生物胺”，由氨基酸衍生的较小化合物。人类大脑包含超过100种不同的肽，它们的很多功能仍不清楚。我的实验室研究这些信号分子是如何起作用的，以及它们是如何引起行为的。我们使用小龙虾和果蝇作为模型实验系统，因为它们比人类和大多数其他动物含有更少的神经细胞，并且许多神经细胞可以很容易地从一个样本到另一个样本进行识别。果蝇基因组被完全测序，提供了一系列“分子工具”，使我们能够确定特定的基因和蛋白质如何允许肽和生物胺改变神经和肌肉细胞的活动。小龙虾具有体积较大的优点，为生化分析提供了更多的材料。我们使用这两个模型系统来确定特定信号分子改变神经元电学特性、肌肉收缩以及最终改变行为的机制。

Nerve cells communicate with each other by releasing chemical signals that alter electrical activity in their target cells. Most of these chemical signals are “peptides” (short chains of amino acids), and some are “biogenic amines”, smaller compounds derived from amino acids. The human brain contains over 100 different peptides, and much about their functions is still not understood. My lab examines how these signaling molecules function and how they give rise to behaviour. We use crayfish and fruit flies as model experimental systems because they contain fewer nerve cells than humans and most other animals, and many of the nerve cells can be identified easily from one specimen to another. The fruit fly genome is fully sequenced, providing an array of “molecular tools” that allow us to determine how specific genes and proteins allow peptides and biogenic amines to alter the activity of nerve and muscle cells. Crayfish have the advantage of larger size, providing more material for biochemical analysis. We use these two model systems to determine the mechanisms through which specific signaling molecules alter the electrical properties of neurons, contraction of muscles and, ultimately, behaviour. During the next five years we will focus mainly on two peptides (proctolin and DPKQDFMRFamide) that are found in fruit flies. Both peptides are neurohormones that induce contraction in muscles and increase the strength of contraction when the muscles are activated by the nerve cells supplying them (motor neurons). We will identify the chemical signaling pathways inside the muscle cells that underlie the effects of these peptides on contraction. In addition to its role as a neurohormone, one of these peptides (proctolin) is released directly onto muscle cells by motor neurons. We will study the consequences of this dual-role of proctolin and determine whether its release from nerve terminals can affect its ction as a circulating hormone. We will also examine the role of proctolin in crawling and turning behaviours exhibited by fruit fly larvae (maggots). We will determine whether proctolin acts within the central nervous system, on muscles or at both sites, and we will identify the cells on which proctolin acts. These studies will increase our understanding of how neuropeptides act on cells and, ultimately, how their actions affect behaviour. This work is important for understanding the fundamental mechanisms underlying behaviour. It is also important to understand how neuropeptides function because they are involved in several diseases.