Molecular and genetic analysis of sleep ontogeny

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Sleep in early life is hypothesized to facilitate structural maturation of the brain. Childhood sleep disturbances portend later neurocognitive deficits and are highly prevalent across neurobehavioral disorders; sleep abnormalities during development may in fact contribute to aberrant neural circuit formation. Improving sleep by targeting regulatory pathways may thus represent a new therapeutic avenue in neurodevelopmental disease. However, the molecular and genetic factors controlling early life sleep remain largely unknown, hindering design of sleep-related strategies. In fact, there are no genes known to specifically influence developmental changes to sleep. Using an RNAi-based genetic screen in Drosophila, we identified a transcription factor, pdm3, that regulates ontogenetic sleep changes. The overall goal of this proposal is to characterize the genetic and molecular pathways controlling sleep ontogenetic changes by investigating the function of PDM3 in Drosophila. Specifically, we will define the cellular mechanisms through which PDM3 controls juvenile sleep (Aim 1) and identify the molecular signals downstream of PDM3 that coordinate sleep ontogeny (Aim 2). We will then manipulate pdm3 to investigate how loss of the juvenile sleep state affects brain and behavioral maturation (Aim 3). Our proposal utilizes a diverse array of approaches, including behavioral, genetic, and imaging. Dissecting the molecular genetic control of sleep ontogeny will yield new insights into the regulation of early life sleep, deepening our understanding of the link between sleep ontogeny and neurobehavioral pathology.