Investigating the neurocircuitry of sleep duration regulation

点击翻译按钮获取中文摘要

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.