REST AND LONG-TERM MEMORY CONSOLIDATION IN DROSOPHILA

描述 (改编自申请者的描述)尽管几十年来专注于 调查发现，睡眠的功能尚不清楚。支持率最高的 假设是睡眠促进了最佳的神经可塑性。考虑到 神经可塑性是无脊椎动物以及高等生物所必需的 脊椎动物，这些研究人员提出，一个可能的功能 睡眠状态对黑腹果蝇的促进作用也是最佳的 神经可塑性。与哺乳动物一样，果蝇的神经可塑性伴随着 长期记忆的巩固，其分子基础是 迅速地被描述为特征。睡意绵绵的休息状态，强劲反弹 在被剥夺后，已经在果蝇的初步研究中被发现。 因此，拟议的研究将集中于：(1)确定 枕形支架的行为和分子特性；以及(2) 测试这种状态是哺乳动物的功能类似物的假设 睡眠可以促进神经的可塑性。两者之间的联系 睡眠般的休息和学习将通过解剖分子链接来研究 REST与环磷酸腺苷反应基因表达之间的关系。阵营反应 基因和调节它们的结合蛋白(CREB)起着至关重要的作用 脊椎动物和脊椎动物在长期记忆巩固中的作用 无脊椎动物，包括果蝇。这些初步研究表明， CREB活性在夜间最高，也就是休眠期。这个 果蝇REST促进LTM的假说将直接通过 操纵休息期和分析长期记忆巩固 从行为上讲。拟议的研究带来了分子工具， 可以很容易地在Drosphila被利用，因为它作为一种 遗传学和神经生物学研究的研究课题。整体而言 假设果蝇的睡眠性休息阶段的功能是 促进适应性神经可塑性，特别是 巩固长期记忆。在具体目标1中，他们将记录 果蝇的睡眠式休息是一种明确的行为综合征。这个 重点将放在与哺乳动物睡眠相似的特征上，以及 开发可作为工具使用的袖珍支撑件的自动化措施 后续研究。《特定目标2》将扩展他们的初步发现 CREB活性在黑暗阶段增加，并检验以下假设 其活性通过特定的分子机制与REST联系在一起。最后， 在具体目标3中，他们将直接测试最优预测 长期记忆巩固(LTM)需要良好巩固的睡眠 休息状态。

DESCRIPTION (Adapted from the applicant's description) Despite decades of focused investigation, the function of sleep is not known. The best-supported hypothesis is that sleep promotes optimal neural plasticity. Given that neural plasticity is a necessity for invertebrates as well as higher vertebrates, these investigators propose that a likely function of a sleeplike rest state in Drosophila melanogaster, is also to promote optimal neural plasticity. As in mammals, neural plasticity Drosophila accompanies the consolidation of long-term memory, the molecular basis of which is rapidly being characterized. A sleeplike rest state, with a robust rebound after deprivation, has been identified in preliminary studies of Drosophila. Therefore, the proposed studies will focus: (1) on determining the behavioral and molecular properties of the sleeplike rest; and (2) on testing the hypothesis that this state is a functional analog of mammalian sleep in that it promotes neural plasticity. The association between sleeplike rest and learning will be studies by dissecting the molecular link between rest and expression of cyclic-AMP responsive genes. cAMP-responsive genes and the binding proteins that regulate them (CREBs) play a critical role in long-term memory consolidation in both vertebrates and invertebrates, including Drosophila. These preliminary studies show that CREB activity is highest during the night, when the rest period occurs. The hypothesis that rest promotes LTM in Drosophila will be tested directly by manipulating the rest period and assaying long term memory consolidation behaviorally. The proposed studies bring to bear the molecular tools that can readily be exploited in Drosphila because of its long history as a research subject in genetic and neurobiological studies. The overall hypothesis is that the function of the sleeplike rest phase in Drosophila is the facilitation of adaptive neural plasticity, specifically the consolidation of Long Term Memory. In Specific Aim 1 they will document that sleeplike rest in Drosophila is a defined behavioral syndrome. The focus will be on features that show analogy to mammalian sleep and on developing automated measures of sleeplike rest for use as tools in the subsequent studies. Specific Aim 2 will extend their preliminary findings that CREB activity increases in the dark phase, and test the hypothesis that its activity is linked to rest by specific molecular mechanisms. Finally, in Specific Aim 3, they will test directly the prediction that optimal long-term memory consolidation (LTM) requires a well-consolidated sleeplike rest states.