Investigating the neurocircuitry of sleep duration regulation

研究睡眠持续时间调节的神经回路

• 批准号: 10311528
• 负责人: YING-HUI FU
• 金额: $ 56.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-19 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311528
• 关键词: ADRB1 gene; Affinity Chromatography; Aging; Anatomy; Brain; Brain region; Calcium; Cell physiology; Cells; Cognition; Cognitive deficits; Electroencephalography; Experimental Designs; Fiber; Genes; Health; Homeostasis; Hour; Human; Image; Intervention; Lead; Life; Light; Link; Location; Maintenance; Maps; Methods; Molecular; Molecular Profiling; Monitor; Mus; Mutant Strains Mice; Mutation; Nature; Nervous System Physiology; Neurons; Neurotoxins; Pathway interactions; Performance; Persons; Pharmacogenomics; Photometry; Play; Polysomnography; Population; Positioning Attribute; Process; Psyche structure; Recording of previous events; Regulation; Reporting; Resistance; Ribosomes; Role; Sleep; Sleep Deprivation; Societies; Synaptic plasticity; System; Testing; Translating; Virus; Wild Type Mouse; Work; base; brain cell; brain dysfunction; cell type; cognitive function; cognitive performance; designer receptors exclusively activated by designer drugs; human subject; insight; mouse model; mutation carrier; neural circuit; neural patterning; neuronal circuitry; non rapid eye movement; optogenetics; poor sleep; relating to nervous system; sleep behavior; sleep quality; sleep quantity; sleep regulation; tool

Abstract Sleep is essential for the maintenance of our cognition and neurological functions, and both quality and quantity of sleep are critical. We likely have known this for the entire human history. Yet, we remain astonishingly ignorant on how the quality and quantity of sleep are regulated. Excitingly, nature has provided us a very small number of human subjects who are genetically wired to sleep shorter hours per day (thus more efficiently). These people usually live a long and healthy (both physically and mentally) life. Identification of genetic changes in these people provides us concrete and specific molecules that are in the sleep duration/efficiency pathway. These molecules offer opportunities to not only map brain regions and cells for sleep regulation but also will lead us to gain understanding of neurocircuitry of sleep duration/efficiency. In this proposal, we will use integrated approaches to understanding how neurocircuit activities work in concert to regulate sleep duration/efficiency. Our hypothesis is that there exist unique neurocircuits for sleep duration and efficiency that are separate from the circuits for sleep-promoting and wake-promoting. Our experimental design outlined here is based on this hypothesis to reveal these circuits in a systematic way. We will first identify specific cell types with our gene-specific Cre mice. We will then generate a functional circuit diagram by mapping their projections. The role and function of these cells in sleep regulation will be tested in the context of circuit by linking the activity of these cells to sleep with precise interventional tools that change neural circuit dynamics. The results from this study will reveal how dynamic patterns of neural activity are transformed into efficient sleep. We will simultaneously monitor sleep state with EEG/EMG recording while actively recording and manipulating dynamic patterns of neural activity of specific cells. The results obtained from this study will provide a fundamental understanding of brain circuits for sleep duration/efficiency maintenance. Since quality sleep is the basis of healthy brain (cognitive and neurological function), understanding of how quality sleep circuit is obtained will not only shed new light on how poor sleep can lead to unhealthy brain but also give insight into mechanisms for treating brain dysfunctions.

抽象的 睡眠对于维持我们的认知和神经功能至关重要，而且睡眠质量和 睡眠量至关重要。我们可能在整个人类历史上都知道这一点。然而，我们仍然 令人惊讶的是，他们对如何调节睡眠的质量和数量一无所知。令人兴奋的是，大自然提供了 我们是极少数人类受试者，他们的基因决定了每天睡眠时间较短（因此更多 有效）。这些人通常过着长寿而健康的生活（无论是身体上还是精神上）。鉴定 这些人的基因变化为我们提供了睡眠中具体且特定的分子 持续时间/效率途径。这些分子不仅提供了绘制大脑区域和细胞的机会 睡眠调节也将使我们了解睡眠持续时间/效率的神经回路。在这个 建议，我们将使用综合方法来理解神经回路活动如何协同工作 调节睡眠持续时间/效率。我们的假设是存在独特的睡眠持续时间和神经回路 与促进睡眠和促进唤醒的电路分开的效率。我们的实验设计 这里概述的就是基于这个假设来系统地揭示这些电路。我们首先会识别 特定细胞类型与我们的基因特异性 Cre 小鼠。然后我们将生成一个功能电路图 绘制他们的预测。这些细胞在睡眠调节中的作用和功能将在以下背景下进行测试 通过使用改变神经回路的精确介入工具将这些细胞的活动与睡眠联系起来 动力学。这项研究的结果将揭示神经活动的动态模式如何转化为 高效睡眠。我们将在主动记录的同时通过脑电图/肌电图记录来监测睡眠状态 以及操纵特定细胞的神经活动的动态模式。这项研究获得的结果将 提供对睡眠持续时间/效率维持的大脑回路的基本了解。由于品质 睡眠是大脑健康（认知和神经功能）的基础，了解睡眠质量如何 获得的电路不仅将为睡眠不足如何导致大脑不健康提供新的线索，而且还可以提供 深入了解治疗脑功能障碍的机制。

项目成果

TIMELESS mutation alters phase responsiveness and causes advanced sleep phase.

TIMELESS 突变会改变时相反应并导致睡眠时相提前。

• 发表时间: 2019-06-11
• 影响因子: 11.1
• 作者: Kurien, Philip;Hsu, Pei;Leon, Jacy;Wu, David;McMahon, Thomas;Shi, Guangsen;Xu, Ying;Lipzen, Anna;Pennacchio, Len A;Jones, Christopher R;Fu, Ying;Ptáček, Louis J
• 通讯作者: Ptáček, Louis J

Recent advances in sleep genetics.

睡眠遗传学的最新进展。

• 发表时间: 2021
• 影响因子: 5.7
• 作者: Webb, John M;Fu, Ying
• 通讯作者: Fu, Ying

Diverse roles of pontine NPS-expressing neurons in sleep regulation.

脑桥 NPS 表达神经元在睡眠调节中的多种作用。

• 发表时间: 2024-02-27
• 影响因子: 11.1
• 作者: Xing, Lijuan;Zou, Xianlin;Yin, Chen;Webb, John M;Shi, Guangsen;Ptáček, Louis J;Fu, Ying
• 通讯作者: Fu, Ying

Human circadian variations.

人类昼夜节律变化。

• 发表时间: 2021-08-16
• 作者: Gentry, Nicholas W;Ashbrook, Liza H;Fu, Ying;Ptáček, Louis J
• 通讯作者: Ptáček, Louis J

A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors.

β1-肾上腺素受体的罕见突变影响睡眠/觉醒行为。

• 发表时间: 2019-09-25
• 影响因子: 16.2
• 作者: Shi, Guangsen;Xing, Lijuan;Wu, David;Bhattacharyya, Bula J;Jones, Christopher R;McMahon, Thomas;Chong, S Y Christin;Chen, Jason A;Coppola, Giovanni;Geschwind, Daniel;Krystal, Andrew;Ptáček, Louis J;Fu, Ying
• 通讯作者: Fu, Ying