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An Essential Role for Corticothalamic Slow Waves in Sleep Regulation

皮质丘脑慢波在睡眠调节中的重要作用

基本信息

批准号：
7938805
负责人：
Jonathan P Wisor
金额：
$ 37.38万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-15 至 2012-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7938805
关键词：
Address Biochemical Brain Cardiovascular Diseases Cell Nucleus Cell physiology Cells Cerebral cortex Cerebrum Data Diabetes Mellitus Educational process of instructing Environment Feedback Frequencies Funding Genetic Models Goals Health Knowledge Lead Link Literature Measures Mediating Mental disorders Neurobiology Neurons Obesity Personal Satisfaction Physiology Population Positioning Attribute Principal Investigator Production Public Health Publications Publishing Pyramidal Cells Recording of previous events Recovery Research Resources Risk Factors Rodent Role Science Secondary to Sleep Sleep Deprivation Sleep Disorders Slow-Wave Sleep Students Techniques Testing Thalamic structure Time United States National Institutes of Health Universities Washington Work base deprivation hippocampal pyramidal neuron innovation meetings neurobehavioral neurochemistry novel public health relevance research study response sleep regulation

项目摘要

DESCRIPTION (provided by applicant): Poor-quality sleep and sleep insufficiency are significant risk factors for physical and mental illness and are, thus, of major public-health concern. Obesity, diabetes and cardiovascular disease are all statistically linked to sleep insufficiency generally and to the disruption of the portion of sleep characterized by slow electroencephalographic (EEG) oscillations ("slow wave sleep"; SWS), specifically. In addition, sleep insufficiency induces neurobehavioral deficits, many of which can be attributed to disruption of SWS. The negative consequences of SWS disruption mandate for additional research on the mechanisms and consequences of slow waves in the sleep EEG. Much work to date has focused on the roles of subcortical neuromodulatory influences and thalamic cell physiology in regulating slow waves. However, the degree to which the electrophysiological oscillations intrinsic to neurons of the cerebral cortex regulate EEG slow wave timing, frequency and amplitude re- mains uncertain. Thus, there is a critical unmet need for further studies on the neurobiological underpinnings of the restorative effects of slow waves. Here, we propose a unique approach that will utilize optogenetic stimulation of cortical pyramidal neurons to manipulate cortical rhythms and measure the effect of this manipulation on slow wave activity. The central hypothesis to be addressed is that slow oscillations (<4 Hz) in the activity of pyramidal neurons are necessary for both the discharge of sleep need and macromolecular changes during sleep. In the proposed experiments, we will test the hypothesis that regular rhythmic activation of pyramidal neurons in the cerebral cortex increases subsequent slow wave activity in the cerebral cortex. We will test the hypothesis that the discharge of excessive sleep need subsequent to SD, as measured by a decline in EEG slow wave activity across time, and the macromolecular response to SD require uninterrupted slow wave activity in the cerebral cortex. The proposed experiments have the potential to identify a novel mechanism by which a cell population within the cerebral cortex regulates EEG slow wave production and sleep need. These experiments, using techniques that the principal investigator has taught to a number of trainees in the past, will meet an unmet need for research opportunities for WSU Spokane's student population in the biomedical sciences. Finally, these experiments will provide data that validate our techniques as a novel way of studying slow wave sleep function, and in so doing, will place us in a strong position to seek expanded NIH funding at the R01 level. PUBLIC HEALTH RELEVANCE: Insufficient sleep has a number of negative effects on health and well-being. We seek to increase our understanding of the causes and consequences of insufficient sleep at the cellular and biochemical levels. We propose to determine whether a class of cells known as pyramidal cells in the cerebral cortex of the brain, serve an essential function in the brain's response to sleep insufficiency. We do so with the anticipation that these studies will lead to potential countermeasures for the health effects of insufficient sleep.

描述（由申请人提供）：睡眠质量差和睡眠不足是身体和精神疾病的重要风险因素，因此是主要的公共卫生问题。肥胖、糖尿病和心血管疾病在统计学上都与睡眠不足有关，特别是与以慢脑电图（EEG）振荡（“慢波睡眠”; SWS）为特征的睡眠部分的中断有关。此外，睡眠不足引起神经行为缺陷，其中许多可归因于SWS的破坏。SWS中断的负面后果要求对睡眠EEG中慢波的机制和后果进行额外的研究。迄今为止，许多工作都集中在调节慢波的皮质下神经调节的影响和丘脑细胞生理的作用。然而，大脑皮层神经元固有的电生理振荡调节EEG慢波定时、频率和振幅的程度仍然不确定。因此，有一个关键的未满足的需要，对慢波的恢复效果的神经生物学基础的进一步研究。在这里，我们提出了一种独特的方法，将利用光遗传学刺激皮质锥体神经元来操纵皮质节律，并测量这种操纵对慢波活动的影响。要解决的中心假设是，锥体神经元活动中的缓慢振荡（<4 Hz）对于睡眠需求的释放和睡眠期间的大分子变化都是必要的。在拟议的实验中，我们将测试的假设，在大脑皮层锥体神经元的定期节律激活增加随后在大脑皮层的慢波活动。我们将测试这一假设，即过度睡眠的放电需要继SD之后，如通过EEG慢波活动随时间的下降所测量的，并且对SD的大分子反应需要大脑皮层中不间断的慢波活动。拟议的实验有可能确定一种新的机制，通过这种机制，大脑皮层内的细胞群调节EEG慢波的产生和睡眠需求。这些实验，使用的技术，主要研究者已经教了一些学员在过去，将满足一个未得到满足的需要，研究机会为WSU斯波坎的学生人口在生物医学科学。最后，这些实验将提供数据，验证我们的技术作为一种研究慢波睡眠功能的新方法，这样做，将使我们处于有利地位，以寻求扩大NIH在R 01水平的资金。公共卫生相关性：睡眠不足对健康和福祉有许多负面影响。我们寻求增加我们的原因和睡眠不足的后果在细胞和生化水平的理解。我们建议确定是否一类细胞被称为大脑皮层的锥体细胞，在大脑的睡眠不足的反应中发挥重要作用。我们这样做的预期是，这些研究将导致睡眠不足对健康影响的潜在对策。