Investigating the neurocircuitry of sleep duration regulation

摘要 睡眠对于维持我们的认知和神经功能至关重要， 睡眠的数量是至关重要的。我们很可能在整个人类历史上就已经知道了这一点。然而，我们仍然 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 我们有一小部分人类受试者，他们的基因决定了他们每天的睡眠时间更短（因此更多）。 效率）。这些人通常过着长寿和健康的生活（身体和精神）。鉴定 这些人的基因变化为我们提供了具体和特定的分子， 持续时间/效率路径。这些分子不仅为绘制大脑区域和细胞提供了机会， 睡眠调节，而且还将引导我们获得对睡眠持续时间/效率的神经回路的理解。在这 建议，我们将使用综合方法来了解神经回路活动如何协同工作， 调节睡眠时间/效率。我们的假设是，存在着独特的神经回路， 与用于促进睡眠和促进唤醒的电路分离的效率。我们的实验设计 这里概述的是基于这一假设，以系统的方式揭示这些电路。我们将首先确定 用我们的基因特异性Cre小鼠来研究特定的细胞类型。然后，我们将生成功能电路图， 绘制他们的投影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： 通过精确的干预工具将这些细胞的活动与睡眠联系起来，改变神经回路， 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记录同时监测睡眠状态 并操纵特定细胞神经活动的动态模式。从这项研究中获得的结果将 提供对维持睡眠持续时间/效率的大脑回路的基本理解。由于质量 睡眠是大脑健康的基础（认知和神经功能），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， 对治疗大脑功能障碍的机制的深入了解。

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.