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交流，这些化学物质包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，而对这种过程的调节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称为SNARE的蛋白质控制的。 尽管进行了深入的研究，但这些SNARE蛋白的功能仍然难以捉摸。 SNARE蛋白在所有动物中高度保守，甚至在酵母中也发现了类似的蛋白。 因此，通过研究果蝇（Drosophila melanogaster）中的SNARE功能，可以将SNARE蛋白的功能应用于所有动物的分泌过程。 使用选定的SNARE突变体，SNARE基因在果蝇中的转基因表达，和一种新的神经肽释放测定，这些蛋白质的功能，神经递质和神经肽释放将被确定。 阐明神经递质和神经肽释放的过程对于理解行为是必不可少的。 神经系统中更复杂的功能，如学习和记忆，涉及突触强度的改变。 改变突触强度的一个主要方法是调节神经递质的释放过程。 如果我们不清楚神经递质释放的基本机制（这也是本书的目标），就很难真正理解学习和记忆的迷人本质。 神经肽在维持生物体内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、睡眠和昼夜节律都由神经肽释放控制。 来自神经和内分泌系统的神经肽分泌物用于精确协调动物体内的器官系统，使它们共同发挥作用，从而达到平衡状态。 因此，确定神经肽的释放是如何控制的，将大大提高我们对所有动物如何调节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拟激素来干扰内分泌功能，本提案中的研究对于定义正常的内分泌功能至关重要。 这些研究也将有助于确定所有真核细胞生存所需的基本分泌过程。 这项工作的结果将发表在科学家广泛阅读的期刊上，所产生的科学材料将随时提供给科学界。 事实上，这样的一个菌株已经被捐赠给了布卢明顿果蝇库存中心，使所有研究人员都可以随时使用。 此外，在康奈尔大学，两门课程将包括这些研究的材料，以扩大这项研究的教育目标。 康奈尔大学多元化的学生群体确保了科学培训将延伸到科学领域代表性不足的少数群体。

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.