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Role of Drosophila circadian circuitry in experience-dependent sleep

果蝇昼夜节律电路在经验依赖性睡眠中的作用

基本信息

批准号：
7795919
负责人：
Jeffrey Michael Donlea
金额：
$ 1.18万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2010-09-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Sleep has been shown to play an important role in the consolidation of memories in humans, rats and flies (Stickgold et-al, 2000, Ganguly-Fitzgerald et al, 2006). Recent studies have shown that, in addition to playing a strong role in sleep regulation, the circadian clock also influences processes associatedwith learning and;memory (Keisler et al, 2007, Decker et al, 2007). Thus, the neuronal circuits that control circadian rhythms are uniquely positioned to play an important role in coordinating interactions between sleep and memory. We have previously shown that wild-type Drosophila exhibit increased sleep after being housed for several days in a socially-enriched environment and that sleep is also increased following training in a courtship conditioning assay that results in the formation of long-term memories (Ganguly- Fitzgerald et al, 2006). This increase in sleep is dependent on canonical learning and memory genes such as the adenylyl cyclase rutabaga and is largest during the initial hours after lights-on suggesting the involvement of the circadian clock. Although I have also found that mutations in two genes that are involved in regulating synaptic plasticity, the dDA1 dopamine receptor and the blistered transcription factor. Both of these genes are endogenously expressed in circadian pacemaker cells. Thus, the proposed experiments will test the hypothesis that circadian clock circuits regulate increased sleep following social enrichment and that this regulation requires the expression of genes known to be involved in memory formation. First, I will test whether expression of the dopamine receptor dDA1 in circadian circuitry is involved in regulation of experience-dependent sleep. Second, I will examine whether expression of the Drosophila homolog to the mammalian Serum Response Factor, blistered, in circadian pacemaker cells is involved in controlling experience-dependent sleep. Finally, I will test the hypothesis that blistered is required for experience- dependent increase of synaptic terminal number in circadian clock cells. Research Relevance: Sleep is necessary for consolidation of newly formed memories into longer lasting associations in humans and in fruit flies. Given the similarities between sleep in humans and in flies and the genetic tools that are available to study the fruit fly, I propose to use the fruit fly as a model system to identify a brain circuit that is involved in regulating sleep after novel social experiences. I hypothesize that cells that have been previously identified as circadian oscillators are involved in the control of experience-dependent sleep.

描述（由申请人提供）：睡眠已被证明在人类、大鼠和苍蝇的记忆巩固中发挥着重要作用（Stickgold 等人，2000；Ganguly-Fitzgerald 等人，2006）。最近的研究表明，除了在睡眠调节中发挥重要作用外，生物钟还影响与学习和记忆相关的过程（Keisler 等，2007；Decker 等，2007）。因此，控制昼夜节律的神经元回路在协调睡眠和记忆之间的相互作用中发挥着重要作用。我们之前已经表明，野生型果蝇在社交丰富的环境中饲养几天后表现出睡眠增加，并且在求偶条件反射训练后睡眠也会增加，从而形成长期记忆（Ganguly-Fitzgerald 等，2006）。这种睡眠的增加取决于典型的学习和记忆基因，例如腺苷酸环化酶芜菁甘蓝，并且在开灯后的最初几个小时内达到最大，表明生物钟的参与。虽然我还发现了两个参与调节突触可塑性的基因的突变，即dDA1多巴胺受体和水泡转录因子。这两个基因均在昼夜节律起搏细胞中内源表达。因此，拟议的实验将检验这样的假设：生物钟电路在社交丰富后调节睡眠增加，并且这种调节需要已知参与记忆形成的基因的表达。首先，我将测试昼夜节律回路中多巴胺受体 dDA1 的表达是否参与经验依赖性睡眠的调节。其次，我将检查昼夜节律起搏细胞中果蝇与哺乳动物血清反应因子（起泡）同源的表达是否与控制经验依赖性睡眠有关。最后，我将检验以下假设：生物钟细胞中突触末端数量的经验依赖性增加需要水泡。研究相关性：对于人类和果蝇来说，睡眠对于将新形成的记忆巩固为更持久的关联是必要的。考虑到人类和果蝇睡眠之间的相似性以及可用于研究果蝇的遗传工具，我建议使用果蝇作为模型系统来识别在新的社会经历后参与调节睡眠的大脑回路。我假设先前被识别为昼夜节律振荡器的细胞参与了经验依赖性睡眠的控制。