Neural mechanisms of sleep loss in Mexican cavefish

墨西哥洞穴鱼睡眠不足的神经机制

• 批准号: 1656574
• 负责人: Alex Keene
• 金额: $ 33.3万
• 依托单位: Florida Atlantic University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656574&HistoricalAwards=false
• 关键词: Neural; mechanisms; sleep; loss; Mexican

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.

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。每个人的睡眠时间差异很大，但人们对大脑化学物质的变化是如何导致睡眠需求差异的知之甚少。为了更多地了解大脑化学物质如何影响睡眠需求，一组在进化过程中失去睡眠需求的鱼正在被研究。数百万年前，墨西哥洞穴鱼被困在洞穴里，从那以后，它们通过大幅减少睡眠来适应这些营养贫乏的环境，尽管我们还不知道大脑的什么变化使这成为可能。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。研究人员比较了穴居鱼和有规律睡眠模式的河中表层鱼大脑中食欲素的产生，并研究了影响食欲素的药物改变穴居鱼睡眠的能力。确定墨西哥洞穴鱼睡眠缺失的化学基础将使我们更好地了解大脑如何正常调节睡眠，以及在进化过程中或需要睡眠的动物的日常生活中，大脑化学的变化如何影响这一关键的生命功能和动物的健康。来自不同种族和社会经济群体的众多本科生将参与这项工作，以及制定社区外展计划，以提高公众特别是老年人社区的科学素养。摘要在动物王国中，睡眠是一种几乎无处不在的行为，但人们对物种之间或种群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，作为独立的种群存在于祖先的有眼的表面形态和同一物种的盲洞形态。在多个独立的墨西哥古猿洞穴种群中，睡眠缺失的趋同进化为研究生态和进化历史在塑造睡眠中的作用提供了独特的机会。该研究计划将确定通过侧线的感觉输入是否直接调节促醒神经肽Orexin的功能，以及Orexin神经解剖学变化对洞穴种群睡眠缺失进化的贡献。在这个项目中产生的工作将有助于我们对睡眠的生物学基础的理解，并有可能扩展到更好地理解人类自然发生的睡眠差异的机制基础。除了促进跨生活学科的科学知识外，该项目还将为学生提供培训和在当地社区推广的机会。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。

项目成果

Cavefish brain atlases reveal functional and anatomical convergence across independently evolved populations

• DOI: 10.1126/sciadv.aba3126
• 发表时间: 2020-09-01
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Jaggard, James B.;Lloyd, Evan;Keene, Alex C.
• 通讯作者: Keene, Alex C.

Automated Measurements of Sleep and Locomotor Activity in Mexican Cavefish

墨西哥穴居鱼睡眠和运动活动的自动测量

• DOI: 10.3791/59198
• 发表时间: 2019
• 期刊: Journal of Visualized Experiments
• 作者: Jaggard, James B.;Lloyd, Evan;Lopatto, Arthur;Duboue, Erik R.;Keene, Alex C.
• 通讯作者: Keene, Alex C.

Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system

• DOI: 10.1002/dvdy.32
• 发表时间: 2019-01
• 期刊: bioRxiv
• 作者: B. A. Stahl;R. Peuß;Brittnee McDole;A. Kenzior;James B. Jaggard;K. Gaudenz;Jaya Krishnan;S. McGaugh;Erik R. Duboue;A. Keene;Nicolas Rohner

Manipulation of Gene Function in Mexican Cavefish

墨西哥洞穴鱼基因功能的操纵

• DOI: 10.3791/59093
• 发表时间: 2019
• 期刊: Journal of Visualized Experiments
• 作者: Stahl, Bethany A.;Jaggard, James B.;Chin, Jacqueline S.R.;Kowalko, Johanna E.;Keene, Alex C.;Duboué, Erik R.
• 通讯作者: Duboué, Erik R.

What Can a Blind Fish Teach Us About Sleep?

关于睡眠，盲鱼能教会我们什么？

• DOI: 10.3389/frym.2019.00103
• 发表时间: 2019
• 期刊: Frontiers for Young Minds
• 作者: Paz, Alexandra;Keene, Alex C.
• 通讯作者: Keene, Alex C.