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: 10058285
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058285
• 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; 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.

摘要 睡眠对于维持我们的认知和神经功能是必不可少的，而睡眠质量和睡眠质量 睡眠时间的长短至关重要。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，他们对睡眠的质量和数量是如何调节的一无所知。令人兴奋的是，大自然提供了 我们是一小部分人类受试者，他们天生每天睡眠时间更短(因此更多 高效)。这些人通常过着健康长寿的生活(无论是身体上还是精神上)。身份识别 这些人的基因变化为我们提供了睡眠中的具体和特定的分子 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图的机会 睡眠调节还将引导我们了解睡眠持续时间/效率的神经回路。在这 提案中，我们将使用综合方法来了解神经回路活动是如何协同工作的 调节睡眠时间/效率。我们的假设是，睡眠持续时间和睡眠时间存在独特的神经回路 与促进睡眠和促进清醒的回路分开的效率。我们的实验设计 这里概述的是基于这一假设来系统地揭示这些电路。我们将首先确定 我们的基因特异性Cre小鼠具有特定的细胞类型。然后，我们将通过以下方式生成功能电路图 绘制他们的预测图。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 通过使用精确的干预工具改变神经回路，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是如何转化为 高效睡眠。我们将在主动记录的同时，通过EEG/EMG记录来同时监测睡眠状态 以及操纵特定细胞神经活动的动态模式。从这项研究获得的结果将 提供对大脑回路的基本了解，以维持睡眠持续时间/效率。自质量以来 睡眠是健康大脑(认知和神经功能)的基础，了解如何高质量的睡眠 电路的获得将不仅为睡眠不足如何导致大脑不健康提供新的线索，而且还将给出 对治疗大脑功能障碍的机制的洞察。