Molecular and genetic analysis of the juvenile sleep state

项目摘要 早期的睡眠被假设为促进大脑结构的成熟。儿童期睡眠障碍 预示着以后的神经认知缺陷，并且在神经行为障碍中非常普遍;睡眠 发育过程中的异常实际上可能会导致异常神经回路的形成。改善睡眠 因此，通过靶向调节途径可能代表了神经发育的新治疗途径。 疾病然而，控制生命早期睡眠的分子和遗传因素在很大程度上仍然未知， 阻碍睡眠相关策略的设计。事实上，没有已知的基因控制发育 睡眠的变化。在果蝇中使用基于RNAi的遗传筛选，我们鉴定了一种转录因子， pdm 3，调节青少年睡眠状态。该提案的总体目标是描述遗传学特征， 和控制青少年睡眠状态的分子途径，通过研究PDM 3的功能， 果蝇具体来说，我们将定义PDM 3控制青少年睡眠的细胞机制 (Aim 1）并确定协调睡眠个体发生的PDM 3下游分子信号（目的2）。我们 然后将操纵pdm 3来研究青少年睡眠状态的丧失如何影响大脑和行为。 成熟（目标3）。我们的建议利用了多种方法，包括行为，遗传和 显像剖析睡眠个体发育的分子遗传控制将产生对睡眠调节的新见解。 早期生活睡眠，加深我们对睡眠个体发育和神经行为之间联系的理解 病理

PROJECT SUMMARY 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 have been no genes known to control developmental changes to sleep. Using an RNAi-based genetic screen in Drosophila, we identified a transcription factor, pdm3, that regulates the juvenile sleep state. The overall goal of this proposal is to characterize the genetic and molecular pathways controlling the juvenile sleep state 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.