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Mechanisms mediating the relationship between temporal coding and sleep

调节时间编码与睡眠之间关系的机制

基本信息

批准号：
10256758
负责人：
Masashi Tabuchi
金额：
$ 24.61万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10256758
关键词：
Academia Animal Model Area Arousal Behavior Behavioral Binding Binding Proteins Biochemical Biochemistry Biology Cells Code Complement Computer Models Data Development Development Plans Drosophila genus Electrophysiology (science)Engineering Environment Exhibits Fellowship Frequencies Functional Imaging Genetic Goals Growth Health Human Image Ions Lead Link Measures Mediating Membrane Mentors Modeling Molecular Molecular Biology Na(+)-K(+)-Exchanging ATPase Neural Pathways Neurons Neurosciences Pathway interactions Pattern Performance Physiology Play Process Pump RNA Interference RNA interference screen Regulation Research Research Personnel Role Scientist Signal Transduction Sleep Sleep disturbances Synapses Testing Time Training Translating Translations Universities Up-Regulation Variant Work awake base career career development circadian circadian pacemaker computational neuroscience driving force extracellular fly improved in vivo ionic balance knock-down mutant neural circuit novel optogenetics overexpression patch clamp postsynaptic predictive modeling receptor relating to nervous system response responsible research conduct scaffold signal processing simulation skills sleep behavior sleep quality

项目摘要

Emerging data suggest that, in addition to sleep amount, sleep quality is important for human health and performance. However, the molecular and neural pathways underlying sleep quality remain unclear. Drosophila is now well-established as a model organism for studying sleep, and my preliminary behavioral and electrophysiological data in Drosophila define a new molecular pathway linking the circadian clock to temporal-specific neural coding to regulate sleep quality. These findings suggest that sleep quality is determined by clock-driven temporal coding in an arousal circuit. Thus, in the proposed work, I will study the relationship between sleep and temporal coding in specific neural circuits. Specifically, I will (1) characterize the molecular mechanisms mediating sleep quality, (2) examine circuit mechanisms underlying temporal coding of sleep quality, and (3) investigate how ionic flux regulates temporal coding of sleep quality. My long-term career goal is to become an independent scientist in academia, and my long-term research goal is to understand how neural coding emerges from specific spike sequences to generate behavioral states such as sleep. To achieve these goals, I will undertake extensive training in molecular biology and biochemistry, in vivo functional imaging, and computational modeling. This new training will complement by previous background in patch-clamp electrophysiology, signal processing skills, Drosophila genetics, and behavioral analyses. The Johns Hopkins University and my mentors and consultants will provide a stellar environment for my scientific growth and guidance in career development. The proposed fellowship will allow me to build my own area of research in neuroscience, and be a competitive investigator with broad expertise from biology to engineering and from molecular and cellular neuroscience to computational neuroscience.

新的数据表明，除了睡眠量，睡眠质量对人类健康和表现也很重要。然而，睡眠质量的分子和神经通路仍然不清楚。果蝇现在已经被公认为研究睡眠的模式生物，我在果蝇身上的初步行为和电生理数据定义了一个新的分子通路，将生物钟与时间特异性神经编码联系起来，以调节睡眠质量。这些发现表明，睡眠质量是由唤醒回路中的时钟驱动的时间编码决定的。因此，在拟议的工作中，我将研究睡眠和特定神经回路中的时间编码之间的关系。具体来说，我将（1）表征介导睡眠质量的分子机制，（2）检查睡眠质量的时间编码的电路机制，（3）研究离子流如何调节睡眠质量的时间编码。我的长期职业目标是成为学术界的独立科学家，我的长期研究目标是了解神经编码如何从特定的尖峰序列中产生，以产生睡眠等行为状态。为了实现这些目标，我将在分子生物学和生物化学，体内功能成像和计算建模方面进行广泛的培训。这种新的培训将补充以前的背景，膜片钳电生理学，信号处理技能，果蝇遗传学和行为分析。约翰霍普金斯大学和我的导师和顾问将为我的科学成长和职业发展提供一流的环境。拟议的奖学金将使我能够建立自己的神经科学研究领域，并成为一名具有竞争力的研究人员，拥有从生物学到工程学，从分子和细胞神经科学到计算神经科学的广泛专业知识。