Investigating the neurocircuitry of sleep duration regulation

研究睡眠持续时间调节的神经回路

基本信息

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
项目类别：
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

项目摘要

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以及质量和质量和睡眠数量至关重要。我们可能在整个人类历史上都知道这一点。但是，我们仍然保持对于如何调节睡眠的质量和数量，令人惊讶的是无知。令人兴奋的是，大自然提供了我们每天都有很少的人类受试者，他们每天睡眠较短（因此更多有效）。这些人通常会过着漫长而健康的生活（身体和精神）生活。识别这些人的遗传变化为我们提供了睡眠中的具体和特定分子持续时间/效率途径。这些分子不仅提供了映射大脑区域和细胞的机会睡眠调节，但也将使我们能够了解睡眠时间/效率的神经记录。在这个提案，我们将使用集成的方法来了解神经电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，睡眠持续时间存在独特的神经循环和效率与促进睡眠和唤醒的电路分开。我们的实验设计此处概述的是基于此假设，以系统的方式揭示这些电路。我们将首先确定特定的细胞类型与我们的基因特异性CRE小鼠。然后，我们将通过映射他们的预测。这些细胞在睡眠调节中的作用和功能将在通过将这些细胞的活性与精确的介入工具联系起来，通过改变神经回路的电路动力学。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的睡眠。我们将同时监视脑电图/EMG记录的睡眠状态，同时录制并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睡眠时间/效率维持的脑电路的基本了解。自质量以来睡眠是健康大脑（认知和神经功能）的基础，了解质量睡眠的方式获得电路不仅会使睡眠不良会导致不健康的大脑有新的启示，而且还会给予深入了解治疗脑功能障碍的机制。