REST AND LONG-TERM MEMORY CONSOLIDATION IN DROSOPHILA

描述 （根据申请人的描述改编）尽管几十年来一直专注于 睡眠的功能尚不清楚。最佳支持 一种假说认为睡眠促进了最佳神经可塑性。鉴于 神经可塑性是无脊椎动物以及高等动物所必需的。 脊椎动物，这些研究人员提出，一个可能的功能， 睡眠类休息状态在果蝇中，也是促进 神经可塑性与哺乳动物一样，果蝇的神经可塑性 长期记忆的巩固，其分子基础是 迅速被定性。一种睡眠般的休息状态，具有强劲的反弹 在对果蝇的初步研究中， 因此，拟议的研究将集中在：（1）确定 睡眠样休息的行为和分子特性;以及（2） 测试假设，这种状态是哺乳动物的功能类似物， 睡眠可以促进神经可塑性。之间的关联 睡眠般的休息和学习将通过解剖分子链来研究 之间的休息和表达环AMP反应基因。camp反应 基因和调节它们的结合蛋白（CREB）在这一过程中起着关键作用。 在脊椎动物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，此时是休息期。的 假设休息促进LTM在果蝇将直接测试 操纵休息期和测定长期记忆巩固 行为上拟议的研究带来了分子工具， 可以很容易地在Drosphila开发，因为它作为一个 遗传学和神经生物学研究的研究课题。整体 一种假说认为，果蝇类睡眠休息期的功能是 适应性神经可塑性的促进，特别是 巩固长期记忆。在具体目标1中，将记录 果蝇的睡眠样休息是一种明确的行为综合征。的 重点将放在与哺乳动物睡眠相似的特征上， 开发睡眠样休息的自动化测量方法， 随后的研究。具体目标2将扩大他们的初步调查结果 CREB活性在黑暗阶段增加，并测试假设， 其活性通过特定的分子机制与休息相关联。最后， 在具体目标3中，他们将直接测试最佳预测， 长期记忆巩固（LTM）需要良好的巩固睡眠， 其余国家。

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.