Sleep Regulation and Function in Early Brain Development

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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.