Neuropeptide modulation of an aversive neural circuit during sleep

项目摘要 数以百万计的美国人患有慢性睡眠障碍，这往往会导致其他共病 例如抑郁症和肥胖症。了解睡眠的分子机制将有助于我们治疗 睡眠障碍睡眠研究人员发现，在编码神经肽的70个人类基因中，有20个基因 与睡眠调节有关。然而，人们对这些神经肽如何与神经元相互作用知之甚少。 调节睡眠的回路我假设睡眠是多种神经肽共同作用的结果。 神经肽是基因编码的神经调质，可以整合环境刺激， 饥饿，然后通过兴奋或抑制靶神经元诱导行为来协调调节行为 states.神经肽在进化上的重要性可以通过神经肽的高度保守性来证明。 从人类到蠕虫的许多神经肽。编码神经肽的基因已经被证明是 调节作用的调节睡眠，我的建议将确定如何这些神经肽的作用， 简单的厌恶神经回路 我将用遗传学上易于处理的简单方法来处理这些关于睡眠的复杂问题。 神经系统（302个神经元）。优雅我将充分利用C的神经系统。 并评估感觉系统在睡眠期间如何被神经肽调节。有122 C.神经肽编码基因我之前的工作发现了一些特定的神经肽 调节睡眠的神经系统。优雅本研究将阐明两类神经肽的功能： RFamides，最近被证明可以调节后生动物门的睡眠，以及速激肽，一种神经肽 与脊椎动物的睡眠有关我的项目将应用下一代神经生物学技术，例如 光遗传学和多神经元成像，以控制和记录睡眠期间神经回路的活动。 光遗传学使用光激活通道和泵来激活和抑制单个神经元。多神经元 成像技术的可视化神经系统的活动在体内，提供了一个窗口，神经科学家 他们可以通过它来观察神经系统的活动。我计划将联合收割机的神经调节研究 光遗传学和多神经元成像在睡眠中的应用。我之前的实验表明， 睡眠是多种神经肽共同作用的结果。我假设这些神经肽的作用是 不同的细胞位点我希望能提供第一个完整的模型来描述神经调质如何调节 睡眠期间的厌恶性神经回路，这将对神经肽能神经系统产生重大的进化影响。 脊椎动物感觉抑制的调节。

Project Summary Millions of Americans suffer from chronic sleep disorders, which often result in other co-morbid conditions such as depression and obesity. Understanding the molecular mechanism of sleep will help us treat sleep disorders. Sleep researchers have found that 20 of the 70 human genes that encode neuropeptides have been implicated in sleep regulation. Yet little is known about how these neuropeptides interact with neural circuits to regulate sleep. I hypothesize that sleep results from the collective action of multiple neuropeptides. Neuropeptides are genetically encoded neuromodulators that can integrate environmental stimuli such as hunger and then coordinately regulate behavior by exciting or inhibiting target neurons to induce behavioral states. The evolutionary importance of neuropeptides is demonstrated by the high level of conservation of many neuropeptides from humans to worms. Genes encoding neuropeptides have been shown to play a key regulatory role in the modulation of sleep, and my proposal will determine how these neuropeptides act on a simple aversive neural circuit during sleep. I will approach these complicated questions about sleep using the genetically tractable and simple nervous system (302 neurons) of C. elegans. I will take advantage of the well-studied nervous system of C. elegans and evaluate how the sensory system is modulated by neuropeptides during sleep. There are 122 neuropeptide encoding genes in C. elegans, and my previous work found a number of specific neuropeptides that regulate sleep in C. elegans. This investigation will elucidate the function of two classes of neuropeptides: RFamides, recently shown to regulate sleep across metazoan phylums, and Tachykinin, a neuropeptide implicated in vertebrate sleep. My project will apply the next generation of neurobiology techniques, such as optogenetics and multi-neuron imaging, to control and record the activity of neural circuits during sleep. Optogenetics uses light-activated channels and pumps to activate and inhibit individual neurons. Multi-neuron imaging techniques for visualization of nervous systems activity in vivo, has provided neuroscientists a window from which they can visualize the activity of a nervous system. I plan to combine the study of neuromodulation with optogenetics and multi-neuron imaging in the context of sleep. My previous experiments suggest that sleep results from the collective action of multiple neuropeptides. I hypothesize that these neuropeptides act at distinct cellular sites. I hope to provide the first complete model that describes how neuromodulators regulate an aversive neural circuit during sleep, which will have major evolutionary implications for the neuropeptidergic regulation of sensory depression in vertebrates.