Investigation of Neuropeptide Signaling Mechanisms that Control Sleep

控制睡眠的神经肽信号机制的研究

• 批准号: 10359989
• 负责人: Christopher George Lorenz Vecsey
• 金额: $ 42.74万
• 依托单位: SKIDMORE COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10359989
• 关键词: Accidents; Acute; Address; Animals; Award; Behavior; Behavioral; Biomedical Research; Brain; Calcium; Cells; Cellular Neurobiology; Cyclic AMP; Dangerousness; Development; Drosophila genus; Drosophila melanogaster; Event; Family; Feeding behaviors; Future; Genetic; Genetic Techniques; Goals; Health; Hour; Human; Individual; Investigation; Knowledge; Light; Mammals; Manuscripts; Modernization; Molecular; Molecular Neurobiology; Nature; Neurons; Neuropeptides; Neurosciences Research; Output; Peptides; Performance at work; Pharmacogenetics; Pharmacology; Pharmacotherapy; Play; Population; Property; Public Health; Publishing; Quality of life; Research; Resources; Role; Signal Transduction; Signaling Molecule; Sleep; Sleep Deprivation; Sleep disturbances; Speed; Students; System; Testing; Training; Wakefulness; Work; base; career; circadian; comorbidity; cost; design; effective therapy; experience; experimental study; fluorescence imaging; fly; genetic approach; genetic manipulation; imaging capabilities; improved; insight; neural circuit; neuromechanism; neuropeptide F; neuropeptide Y; optogenetics; prevent; response; side effect; sleep abnormalities; sleep behavior; sleep pattern; sleep quality; sleep regulation; symposium; undergraduate student

Sleep disturbances are increasingly common and are associated with a variety of comorbidities and other public health consequences. It is therefore critical to improve our understanding of the neural mechanisms that control the timing and quality of sleep. Key signaling molecules that regulate sleep in animals ranging from flies to humans come from the family of neuropeptide transmitters. These molecules have sparse expression levels and selective effects on behavior, including sleep, making them prime candidates for the development of focused drug treatments with minimal side effects. However, the mechanisms by which these molecules act individually and in concert to regulate target cells in the brain and thus behavior are poorly understood. This renewal application will take advantage of the powerful genetics and relatively simple sleep network organization of the fruit fly, Drosophila melanogaster, to address how neuropeptides function at the molecular, cellular, and behavioral levels to regulate sleep. In Aim 1, we will utilize optogenetic activation of specific subsets of neurons expressing the sleep-promoting transmitter short neuropeptide F (sNPF) in order to determine their particular roles in sleep regulation. In Aim 2, we will coactivate sleep-promoting sNPF neurons and wake-promoting neurons to determine their hierarchical organization in sleep regulation. In Aim 3, we will utilize live fluorescent imaging to test the hypothesis that sNPF acts as an inhibitory output signal onto leucokinin neurons that regulate sleep. In combination, the proposed work will allow us to establish how sNPF neurons function within sleep regulatory networks in the brain, expanding our understanding of the mechanisms that control sleep and wakefulness at the molecular and circuit levels. In turn, this knowledge will provide a basis for the design of more effective treatments of human sleep abnormalities. This R15 AREA renewal proposal will directly involve undergraduate students in all aspects of the research, including designing and carrying out studies involving techniques of genetic manipulation, molecular and cellular neurobiology, and behavioral analysis. Students will also take an active role in disseminating the scientific knowledge acquired through their research, in the form of conference presentations and published manuscripts. Their experiences will provide formative training for future careers in biomedical fields.

睡眠障碍越来越常见，并与各种合并症和其他公共疾病有关。 健康后果。因此，关键是要提高我们的神经机制，控制 睡眠的时间和质量。调节动物睡眠的关键信号分子， 人类来自神经肽传递素家族。这些分子具有稀疏的表达水平， 对行为的选择性影响，包括睡眠，使他们成为发展集中注意力的主要候选人。 副作用最小的药物治疗。然而，这些分子单独作用的机制 并协同调节大脑中的靶细胞，因此对行为知之甚少。此续订 应用程序将利用强大的遗传学和相对简单的睡眠网络组织的优势， 果蝇，果蝇，以解决如何神经肽功能在分子，细胞， 行为水平来调节睡眠。在目标1中，我们将利用特定神经元亚群的光遗传学激活， 表达促进睡眠的递质短神经肽F（sNPF），以确定其特定的 在睡眠调节中的作用在目标2中，我们将共激活促进睡眠的sNPF神经元和促进觉醒的sNPF神经元。 神经元，以确定它们在睡眠调节中的层次结构。在目标3中，我们将利用活荧光 成像以检验sNPF作为抑制性输出信号作用于调节白细胞激肽神经元的假设。 睡吧结合起来，拟议的工作将使我们能够建立sNPF神经元在睡眠中的功能 大脑中的调节网络，扩大我们对控制睡眠的机制的理解， 分子和电路层面的觉醒。反过来，这些知识将为设计更多的 有效治疗人类睡眠异常。R15区域更新提案将直接涉及 本科生在研究的各个方面，包括设计和开展研究，涉及 遗传操作技术、分子和细胞神经生物学以及行为分析。学生将 在传播通过其研究获得的科学知识方面也发挥积极作用， 会议报告和出版的手稿。他们的经验将为未来提供形成性培训 生物医学领域的职业。