Neural mechanisms of sleep loss in Mexican cavefish

虽然睡眠在动物界几乎是普遍存在的，但调节睡眠的生物学因素仍不清楚。睡眠持续时间在个体之间差异很大，但人们对大脑化学物质的变化如何导致睡眠需求的差异知之甚少。为了了解更多关于大脑化学物质如何影响睡眠需求的信息，研究人员正在研究一组在进化过程中失去睡眠需求的鱼类。墨西哥洞穴鱼在数百万年前被困在洞穴中，并通过大幅减少睡眠来适应这些营养不良的环境，尽管我们还不知道大脑的变化使其成为可能。这个项目的工作是测试睡眠需求的变化是否与促进一种叫做食欲素的化学物质产生的感觉过程的改变有关。研究人员正在比较洞穴鱼和相关的、生活在河流中的、有规律睡眠模式的水面鱼类大脑中食欲素的产生，同时也在研究影响食欲素的药物改变洞穴鱼睡眠的能力。确定墨西哥洞穴鱼睡眠不足的化学基础将使我们能够更好地了解大脑通常如何调节睡眠，以及大脑化学的变化如何在需要睡眠的动物的进化时间或日常生活中影响这一关键的生命功能和动物的福祉。许多来自不同种族和社会经济群体的大学生将参与这项工作，以及开发社区外展计划，以提高公众的科学素养，特别是在老年人社区。然而，人们对导致物种之间或群体中个体之间睡眠差异的功能和进化原理知之甚少。墨西哥洞穴鱼Astyanax mexicanus，作为同一物种的祖先眼睛表面变体和盲洞变体的独立种群存在。多个独立A.墨西哥洞穴的人口提供了一个独特的机会来研究生态学和进化历史在塑造睡眠中的作用。这项研究计划将确定通过侧线的感觉输入是否直接调节唤醒促进神经肽Orexin的功能，以及Orexin神经解剖学变化对洞穴人群睡眠丧失演变的贡献。在这个项目中产生的工作将有助于我们了解睡眠的生物学基础，并有可能扩展到更好地了解人类自然发生的睡眠差异的机制基础。除了为生活学科的科学知识做出贡献外，该项目还将为学生培训和在当地社区开展外联活动提供机会。将与当地一所高中合作开发教学工具，让学生接触行为生态学和神经科学研究。所有开发的实验室协议将在网上提供，供其他高中和教学机构访问和使用。此外，该项目将资助参加第一代和少数民族大学生项目的学生在研究实验室工作。

General AbstractWhile sleep is nearly universal in the animal kingdom, the biological factors regulating sleep remain unclear. Sleep duration varies greatly between individuals, but little is known about how variation in brain chemistry may underlie differences in sleep need. To learn more about how brain chemistry affects sleep need, a group of fish that have lost the need to sleep during their evolution are being studied. Mexican cavefish were trapped in caves millions of years ago, and have since adapted to these nutrient-poor environments by dramatically reducing sleep, though we do not yet know what changes in the brain make that possible. Work in this project tests if changes in sleep need are associated with alterations sensory processes that promote the production of a chemical called Orexin. Orexin production in the brain is being compared between cavefish and related, river-dwelling surface fish with regular sleep patterns, and the ability of drugs that influence Orexin to alter sleep in cavefish is also being examined. Determining the chemical basis for sleep loss in Mexican cavefish will enable us to better understand how the brain normally regulates sleep, as well as how changes in brain chemistry, across evolutionary time or day-to-day in animals that need sleep, affect this critical life function and an animal's well-being. Numerous undergraduates from diverse racial and socioeconomic groups will participate in this work, as well as in developing community outreach programs that will use enhance scientific literacy in the public at large and in senior citizen communities in particular.Technical AbstractSleep is a nearly ubiquitous behavior throughout the animal kingdom, yet little is known about the functional and evolutionary principles driving sleep differences between species or individuals within a population. The Mexican cavefish Astyanax mexicanus, exists as independent populations of an ancestral eyed surface morph and blind cave morphs of the same species. The convergent evolution of sleep loss in multiple independent A. mexicanus cave populations provides the unique opportunity to examine the role of ecology and evolutionary history in shaping sleep. This research program will determine whether sensory input through the lateral line directly modulates function of the wake-promoting neuropeptide Orexin and the contributions of changes in Orexin neuroanatomy to the evolution of sleep loss in cave populations. Work produced in this project will contribute to our understanding of the biological basis of sleep with potential extension to a better understanding of the mechanistic basis of naturally occurring sleep differences in humans. In addition to contributing to scientific knowledge across life disciplines, this project will provide opportunities for student training and outreach in the local community. Teaching tools will be developed in collaboration with a local high school to expose students to behavioral ecology and neuroscience research. All developed lab protocols will be made available online for access and use at other high schools and teaching institutions. Additionally, this project will fund students enrolled in programs for first generation and minority college students to work in the research laboratory.