Functional Analysis of Sleep Promoting Neurons in Health and Disease

描述(申请人提供)：我们已经确定了一组~20个神经元，可以使用果蝇遗传学按需激活。在这些神经元激活期间观察到的睡眠符合识别睡眠的历史定义。我们的数据强调了这些神经元对调节睡眠的重要性。在这项提议中，我们将使用活细胞成像和来自果蝇大脑的活体电生理记录来确定这些神经元在完整大脑中的特性。利用果蝇遗传学诱导睡眠的能力提供了一个独特的机会，可以检查睡眠是否可以用作减缓或减轻与退行性疾病相关的认知障碍的治疗方法。因此，我们将确定在帕金森氏症和阿尔茨海默病的果蝇模型中诱导睡眠是否可以抵消认知行为的缺陷。 公共卫生相关性：睡眠不足和睡眠中断会导致发病率和死亡率增加，并可能在神经退行性疾病期间加速认知障碍。我们建议使用遗传学来从功能上评估健康和疾病期间促进睡眠的神经元。我们将在阿尔茨海默氏症和帕金森氏病的动物模型中确定睡眠是否可以减轻或减轻病理。

DESCRIPTION (provided by applicant): We have identified a group of ~20 neurons that can be activated on-demand using Drosophila genetics. The sleep observed during activation of these neurons meets the historical definition for identifying sleep. Our data highlight the importance of these neurons for regulating sleep. In this proposal we will use live-cell imaging and in vivo electrophysiological recording from Drosophila brains to define the properties of these neurons in the intact brain. The ability to use Drosophila genetics to induce sleep provides a unique opportunity to examine whether sleep can be used as a therapeutic for slowing or attenuating cognitive impairments associated with degenerative diseases. Thus, we will determine whether inducing sleep in Drosophila models of Parkinson's and Alzheimer's disease can offset deficits in cognitive behavior. PUBLIC HEALTH RELEVANCE: Insufficient sleep and sleep disruption result in increased morbidity, mortality and may accelerate cognitive impairments during neurodegenerative disease. We propose to use genetics to functionally evaluate sleep promoting neurons during health and disease. We will determine whether sleep can mitigate or attenuate pathology in animal models of Alzheimer's and Parkinson's disease.