Identification neurons controlling sleep/wake in the nematode C. elegans

识别控制线虫睡眠/觉醒的神经元 秀丽隐杆线虫

• 批准号: 8868312
• 负责人: Christopher Fang-Yen
• 金额: $ 19.37万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8868312
• 关键词: Ablation; Affect; Afferent Neurons; Animal Model; Animals; Arousal; Behavior; Behavioral; Behavioral Genetics; Biological Assay; Biological Models; Biology; Caenorhabditis elegans; Calcium; Characteristics; Circadian Rhythms; Diagnosis; Direct Costs; Disease; Drosophila genus; Facilities and Administrative Costs; Future; Gene Expression; Genes; Genetic; Genotype; Goals; Health; Homeostasis; Human; Image; Institute of Medicine (U.S.); Interneurons; Lasers; Lighting; Locomotion; Mammals; Measurement; Measures; Mediating; Methods; Molecular; Molecular Genetics; Movement; Nematoda; Nervous system structure; Neuroanatomy; Neurobiology; Neurons; Optics; Personal Satisfaction; Phenotype; Physiological; Productivity; Proteins; Public Health; Pump; Regulation; Research; Role; Sensory; Series; Signal Pathway; Sleep; Sleep Disorders; Speed; Staging; Stimulus; Techniques; Technology; Testing; Vision; Work; base; behavioral study; circadian pacemaker; feeding; gene function; image processing; improved; innovation; knowledge base; neural circuit; neuronal circuitry; novel; optical imaging; optogenetics; public health relevance; research study; response; sleep regulation; tool

 DESCRIPTION (provided by applicant): Despite the importance of sleep to our well-being and its impact on disease and work productivity, our cellular and molecular understanding of sleep regulation is limited. Sleep/wake regulation arises via the interaction between neurons. We are investigating the regulation of a sleep behavior during larval transitions called lethargus in the roundworm C. elegans. Lethargus shows both behavioral and molecular genetic similarities to sleep in mammals and Drosophila. Since identifying the neuronal circuit regulating sleep is the next step in the analysis of this behavior, we propose to identify sleep-regulating neurons in C. elegans. In Aim 1 we will conduct an optogenetic screen for interneurons that modulate feeding and locomotion rate, as sleep is characterized by cessation of these behaviors. In Aim 2 we will test whether candidate sleep-modulating interneurons identified in Aim 1 affect sleep-like sensory arousal thresholds and behavioral quiescence. We will also establish the order of action of sleep/wake active neurons. Our studies will make use of innovative optogenetic stimulation, optical imaging, and image processing technologies for perturbing neurons, quantifying feeding movements, measuring quiescence behavior, and measuring arousal thresholds. Our overall goal of identifying every interneuron modulating sleep/wake in an animal is a goal never before accomplished in any animal, yet it is feasible in C. elegans due to the simplicity of its nervous system. Our experiments will provide a knowledge base for mechanistic studies of genes affecting C. elegans sleep-like behavior as well as for physiological studies of sleep-regulating neurons.

 描述（由申请人提供）：尽管睡眠对我们的健康及其对疾病和工作效率的影响很重要，但我们对睡眠调节的细胞和分子理解有限。睡眠/觉醒调节通过神经元之间的相互作用产生。我们正在研究蛔虫C.优美的Lethargus在行为和分子遗传学上与哺乳动物和果蝇的睡眠相似。由于识别调节睡眠的神经元回路是分析这种行为的下一步，我们建议识别C。优雅的在目标1中，我们将对调节进食和运动速率的中间神经元进行光遗传学筛选，因为睡眠的特征是这些行为的停止。在目标2中，我们将测试目标1中确定的候选睡眠调节中间神经元是否影响睡眠样感觉唤醒阈值和行为静止。我们还将建立睡眠/觉醒活动神经元的作用顺序。我们的研究将利用创新的光遗传学刺激，光学成像和图像处理技术来干扰神经元，量化进食运动，测量静止行为和测量唤醒阈值。我们的总体目标是识别动物中调节睡眠/觉醒的每一个中间神经元，这是一个从未在任何动物中实现的目标，但在C.由于其神经系统的简单性，我们的实验将为研究影响C.线虫类睡眠行为以及睡眠调节神经元的生理学研究。