Mechanisms mediating the relationship between temporal coding and sleep

新出现的数据表明，除了睡眠时间，睡眠质量对人类的健康和表现也很重要。然而，睡眠质量背后的分子和神经通路仍不清楚。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条新的分子途径，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，睡眠质量是由生物钟驱动的唤醒回路中的时间编码决定的。因此，在提议的工作中，我将研究睡眠与特定神经回路中时间编码之间的关系。具体来说，我将(1)描述调节睡眠质量的分子机制，(2)研究睡眠质量时间编码的电路机制，以及(3)研究离子通量如何调节睡眠质量的时间编码。我的长期职业目标是在学术界成为一名独立的科学家，我的长期研究目标是了解神经编码是如何从特定的脉冲序列中产生的，从而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接受广泛的训练。这项新的培训将补充以前在膜片钳电生理学、信号处理技能、果蝇遗传学和行为分析方面的背景知识。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个良好的环境。这个提议的奖学金将允许我在神经科学领域建立自己的研究领域，并成为一个具有广泛专业知识的有竞争力的研究者，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。

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.