Molecular Mechanisms of Neurosecretion

所有动物的神经系统都是由称为神经元的细胞组成的。这些神经元通过释放(分泌)称为神经递质和神经肽的化学物质包来相互通信，这些化学物质向其他神经元发出信号。这种神经元间的交流是神经系统处理信息的方式，而这一过程的调制是学习和记忆的基础。神经递质和神经肽的释放被认为是由一组名为SNARES的蛋白质控制的。尽管进行了深入的研究，但这些圈套蛋白的功能仍然不得而知。SNARE蛋白在所有动物中都高度保守，甚至在酵母中也发现了类似的蛋白。因此，通过对果蝇SNARE功能的研究，可以将SNARE蛋白的功能应用于所有动物的分泌过程。通过选择SNARE突变体，在果蝇中转基因表达SNARE基因，以及一种新的神经肽释放实验，这些蛋白在神经递质和神经肽释放中的功能将被确定。阐明神经递质和神经肽的释放过程对于理解行为是至关重要的。神经系统中更复杂的功能，如学习和记忆，涉及突触强度的变化。改变突触强度的一个主要方法是通过调节神经递质的释放过程。如果不清楚神经递质释放的基本机制(这项提议的目标)，就不太可能真正理解学习和记忆的迷人本质。神经肽在维持机体动态平衡方面还有其他重要功能。水平衡、生殖行为、口渴、饥饿、代谢调节、压力、睡眠和昼夜节律都是由神经肽释放控制的。神经和内分泌系统的神经肽分泌被用来精确地协调动物体内的器官系统，使它们一起发挥作用，导致平衡状态。因此，确定神经肽释放是如何调控的，将极大地提高我们对所有动物如何调控这些复杂器官系统的理解。鉴于有证据表明，环境污染物能够通过模仿荷尔蒙来扰乱内分泌功能，这项建议中的研究对于定义正常的内分泌功能至关重要。这些研究还将有助于确定所有真核细胞赖以生存的基本分泌过程。这项工作的结果将发表在供科学家广泛阅读的期刊上，科学界将很容易获得所产生的科学材料。事实上，一种这样的菌株已经捐赠给布鲁明顿果蝇库存中心，让所有研究人员都能轻易获得。此外，在康奈尔大学，两门课程将包含这些研究的材料，以扩展这项研究的教育目标。康奈尔大学多样化的学生群体确保了科学培训将扩展到科学界代表性较低的少数族裔。

The nervous system of all animals is composed of cells called neurons. These neurons communicate with each other by releasing (secreting) packets of chemicals called neurotransmitters and neuropeptides which signal other neurons. This interneuronal communication is the way the nervous system processes information, and modulation of this process underlies learning and memory. The release of neurotransmitters and neuropeptides is thought to be controlled by a set of proteins called the SNAREs. Just how these SNARE proteins function has remained elusive despite intensive study. The SNARE proteins are highly conserved in all animals and similar proteins have even been identified in yeast. Thus, by studying SNARE function in the fruit fly Drosophila melanogaster, the function of the SNARE proteins can be applied to the secretory process in all animals. With the use of selected SNARE mutants, transgenic expression of SNARE genes in Drosophila, and a novel neuropeptide release assay, the function of these proteins in neurotransmitter and neuropeptide release will be determined. Elucidating the process of neurotransmitter and neuropeptide release is essential for understanding behavior. More complex functions in the nervous system such as learning and memory involve alterations in synaptic strength. One major way of altering synaptic strength is by modulating the process of neurotransmitter release. Without a clear understanding of the fundamental mechanism of neurotransmitter release (the goal of this proposal), there is little chance of truly understanding the fascinating nature of learning and memory. Neuropeptides have other crucial functions in maintaining organismal homeostasis. Water balance, reproductive behavior, thirst, hunger, metabolic regulation, stress, sleep, and circadian rhythms are all controlled by neuropeptide release. Neuropeptide secretions from the nervous and endocrine systems are used to precisely coordinate organ systems within the animal so that they function together, leading to a state of balance. Thus, determining how neuropeptide release is governed will greatly improve our understanding of how all animals regulate these complex organ systems. In light of evidence that environmental pollutants are capable of disrupting endocrine function by mimicking hormones, the studies in this proposal are crucial for defining normal endocrine function. These studies will also contribute to the defining the basic process of secretion on which all eukaryotic cells need for survival. The results of this work will be published in widely read journals for scientists and the scientific materials produced will be readily available to the scientific community. In fact, one such strain has already been donated to the Bloomington Drosophila Stock Center, making it readily available to all researchers. Furthermore, at Cornell University, two courses will include material from these studies to extend the educational goals of this research. Cornell's diverse student body ensures that scientific training will extend to underrepresented minorities in the sciences.