Sleep Regulation and Function in Early Brain Development

在早期发育阶段的睡眠在大脑成熟中起着至关重要的作用。然而，调节早期发育睡眠的神经回路和机制还不清楚。此外，由于缺乏一个易于处理的模型系统，对神经发育早期阶段睡眠功能的研究受到限制。在这里，我建议使用果蝇幼虫作为一个平台，解剖电路调节早期发育睡眠。我们的实验室在有限的人群中进行了神经元激活筛选，以确定驱动果蝇幼虫睡眠的神经元子集。我将描述这个屏幕中识别的促进睡眠的神经元，并确定这些神经元释放的促进睡眠的因子。然后，我将评估已识别的睡眠促进神经元与已知的唤醒促进章鱼胺神经元的连接，以深入了解睡眠的逻辑：早期发育期间的唤醒调节。利用永生遗传学，我将标记促进睡眠的神经元，以确定它们在成人大脑中的命运和功能。我们以前的工作已经证明，早期睡眠剥夺会损害神经增殖。然而，目前还不清楚发育期间的睡眠剥夺如何影响成年人大脑的模式。我将研究生命早期睡眠剥夺对蘑菇体（MB）发育的影响，这是一个特征鲜明的昆虫学习中心。我将确定如何结构和功能的MB被睡眠剥夺改变，并进一步评估的影响，在成年苍蝇的MB依赖的学习范式。最后，我将进行RNA-seq来识别耦合睡眠和神经增殖的新基因。总之，拟议的实验将确定调节发育定时睡眠的电路，并提供对神经发育最早阶段睡眠功能的深入了解。

Sleep during early developmental periods plays a critical role in brain maturation. However, the neural circuits and mechanisms regulating early developmental sleep are not well understood. Furthermore, investigations into the function of sleep during the earliest stages of neural development have been restricted by the lack of a tractable model system. Here, I propose using Drosophila larvae as a platform for dissecting the circuits regulating early developmental sleep. Our lab has performed a neuronal activation screen in restricted populations to determine subsets of neurons that drive sleep in Drosophila larvae. I will characterize sleep- promoting neurons identified in this screen and determine the sleep-promoting factors released by these neurons. I will then assess the connectivity of identified sleep-promoting neurons with known wake-promoting octopamine neurons to gain insight into the logic of sleep:wake regulation during early development. Using immortalization genetics, I will label sleep-promoting neurons to determine their fate and function in the adult brain. Our previous work has demonstrated that early-life sleep deprivation impairs neural proliferation. However, it is unclear how sleep-deprivation during development affects patterning of the adult brain. I will examine the effects of early-life sleep deprivation on the development of the Mushroom Body (MB), a well- characterized insect learning center. I will determine how structure and function of the MB are altered by sleep deprivation, and further assess the effects on a MB-dependent learning paradigm in adult flies. Finally, I will perform RNA-seq to identify novel genes coupling sleep and neural proliferation. Together, the proposed experiments will identify circuits regulating developmentally-timed sleep and provide insight into the function of sleep in the earliest stages of neural development.