CAREER: Bidirectional Control of Sleep and Wakefulness by the Hypothalamic Arcuate Nucleus

职业：下丘脑弓状核对睡眠和觉醒的双向控制

• 批准号: 1652060
• 负责人: Matthew Carter
• 金额: $ 58.6万
• 依托单位: Williams College
• 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: 2017-06-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1652060&HistoricalAwards=false
• 关键词: CAREER; Bidirectional; Control; Sleep; Wakefulness

Despite the fact that sleep is universal across the animal kingdom and occupies a substantial portion of an animal's lifetime, the regulation of sleep and wakefulness by the brain is poorly understood. Additionally, national surveys show that sleep is poorly understood among the general public and that many Americans, particularly students, are extremely sleep deprived. Therefore, this project integrates a series of research and educational goals to impact our understanding of the brain mechanisms that control mammalian sleep. The PI will manipulate two populations of neurons (called AgRP neurons and POMC neurons) in rodent brains using powerful genetic technologies to determine their roles in regulating sleep/wake behavior. These groups of neurons are well-known for sensing the nutritional and caloric needs of the body, and so our research will study how food intake affects states of sleep and wakefulness. This work will thus increase our understanding of how the brain coordinates complex behavioral states, in this case hunger and sleep. The educational goals will broaden the impact of this project by including undergraduates in all aspects of this research and by implementing a new course at Williams College on the science of sleep. This course will produce educational materials on sleep that will be freely available and distributed. Together, the research and educational components of this award will increase the United States' competitiveness in science and technology, particularly in the field of neuroscience. The goal of this project is to determine how neurons that regulate energy homeostasis also regulate sleep. Previous studies indicate that sleep/wake states are significantly affected by food need and availability, but the role of neurons that regulate food intake in sleep/wake behavior is unknown. The hypothalamic arcuate nucleus contains two populations of neurons that regulate food intake behavior: orexigenic agouti-related protein (AgRP)-expressing neurons and anorexigenic pro-opiomelanocortin (POMC)-expressing neurons. Preliminary evidence from our laboratory suggests that AgRP neurons can independently promote wakefulness and food intake and that POMC neurons maintain sleep states in addition to suppressing appetite. Previous data also suggest that AgRP and POMC neurons might influence sleep/wake states by projecting to hypocretin-expressing neurons and melanin-concentrating hormone-expressing neurons, respectively, in the lateral hypothalamus. This project will use cutting-edge optogenetic and chemogenetic methods in combination with electroencephalography (EEG) and behavioral analyses to increase our understanding of these systems in sleep/wake behavior and thus how the brain coordinates complex behavioral states. Undergraduate students will be involved in all aspects of this work, which will further impact the field of neuroscience through the hands-on training it will provide for the next generation of scientists and educators.

尽管睡眠在动物界是普遍存在的，并且占据了动物一生的很大一部分，但对大脑对睡眠和觉醒的调节知之甚少。 此外，全国性的调查显示，公众对睡眠的了解很少，许多美国人，特别是学生，睡眠严重不足。 因此，该项目整合了一系列研究和教育目标，以影响我们对控制哺乳动物睡眠的大脑机制的理解。 PI将使用强大的遗传技术操纵啮齿动物大脑中的两个神经元群体（称为AgRP神经元和POMC神经元），以确定它们在调节睡眠/觉醒行为中的作用。 这些神经元群以感知身体的营养和热量需求而闻名，因此我们的研究将研究食物摄入如何影响睡眠和清醒状态。因此，这项工作将增加我们对大脑如何协调复杂行为状态的理解，在这种情况下，饥饿和睡眠。 教育目标将扩大该项目的影响，包括本科生在本研究的各个方面，并通过实施一个新的课程在威廉姆斯学院的睡眠科学。 本课程将制作有关睡眠的教育材料，这些材料将免费提供和分发。该奖项的研究和教育部分将共同提高美国在科学和技术方面的竞争力，特别是在神经科学领域。 该项目的目标是确定调节能量稳态的神经元如何调节睡眠。 先前的研究表明，睡眠/觉醒状态受到食物需求和可用性的显著影响，但调节食物摄入的神经元在睡眠/觉醒行为中的作用尚不清楚。 下丘脑弓状核包含两个群体的神经元，调节食物摄入行为：食欲的刺豚鼠相关蛋白（AgRP）表达神经元和食欲的阿黑皮素原（POMC）表达神经元。 我们实验室的初步证据表明，AgRP神经元可以独立地促进觉醒和食物摄入，POMC神经元除了抑制食欲外还能维持睡眠状态。 之前的数据还表明，AgRP和POMC神经元可能分别通过投射到下丘脑外侧的下丘脑分泌素表达神经元和黑色素浓缩激素表达神经元来影响睡眠/觉醒状态。 该项目将使用尖端的光遗传学和化学遗传学方法，结合脑电图（EEG）和行为分析，以增加我们对睡眠/清醒行为中这些系统的理解，从而了解大脑如何协调复杂的行为状态。本科生将参与这项工作的各个方面，这将通过为下一代科学家和教育工作者提供的实践培训进一步影响神经科学领域。

项目成果

Identification of discrete, intermingled hypocretin neuronal populations

• DOI: 10.1002/cne.24490
• 发表时间: 2018-12-15
• 期刊: JOURNAL OF COMPARATIVE NEUROLOGY
• 影响因子: 2.5
• 作者: Iyer, Manasi;Essner, Rachel A.;Carter, Matthew E.
• 通讯作者: Carter, Matthew E.

Activation of oxytocinergic neurons enhances torpor in mice

• DOI: 10.1007/s00360-023-01528-y
• 发表时间: 2024-01-03
• 期刊: JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMS AND ENVIRONMENTAL PHYSIOLOGY
• 影响因子: 2
• 作者: Hare，Maia T.;Carter，Matthew E.;Swoap，Steven J.
• 通讯作者: Swoap，Steven J.

Neuroethology: Regulation of pre-sleep behaviors

神经行为学：睡前行为的调节

• DOI: 10.1016/j.cub.2022.01.009
• 发表时间: 2022
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Carter, Matthew E.