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

• 批准号: 7672630
• 负责人: Jeffrey Michael Donlea
• 金额: $ 2.76万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672630
• 关键词: Adenylate Cyclase; Area; Biological Assay; Biological Models; Brain; Bulla; Cells; Circadian Rhythms; Confocal Microscopy; Courtship; Data; Dopamine Receptor; Drosophila genus; Elements; Environment; Exhibits; Gene Expression; Genes; Genetic; Homologous Gene; Hour; Housing; Human; Label; Lateral; Learning; Maps; Measures; Memory; Mutation; Neurons; Olfactory Learning; Phenotype; Phosphorus; Pigments; Play; Positioning Attribute; Presynaptic Terminals; Process; Proteins; Rattus; Regulation; Research; Role; Rutabaga; Serum Response Factor; Signal Transduction; Sleep; Synaptic plasticity; Testing; Training; circadian pacemaker; conditioning; experience; fly; long term memory; mutant; novel; prevent; receptor; research study; sleep regulation; social; tool; transcription factor; vesicle-associated membrane protein

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）：已经证明睡眠在人类，大鼠和苍蝇的记忆巩固中起着重要作用（Stickgold et-Al，2000，Ganguly-Fitzgerald等，2006）。最近的研究表明，除了在睡眠调节中发挥重要作用外，昼夜节律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电路在协调睡眠与记忆之间的相互作用中起着重要作用。我们以前已经表明，在富含社会的环境中饲养几天后，野生型果蝇表现出增加的睡眠，并且在训练条件调节测定法中训练后，睡眠也增加了，从而导致长期记忆形成（Ganguly-Fitzgerald等人，2006年）。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rutabaga，在灯光亮起后的最初几个小时，这表明昼夜节律的参与。尽管我还发现，在调节突触可塑性的两个基因中的突变，DDA1多巴胺受体和起泡的转录因子。这两个基因均在昼夜节律起搏器细胞中表达。因此，提出的实验将检验以下假设：昼夜节律时钟电路调节社会富集后的睡眠增加，并且该调节需要已知与记忆形成有关的基因的表达。首先，我将测试昼夜节律中多巴胺受体DDA1的表达是否参与了经验依赖性睡眠的调节。其次，我将检查果蝇同源物与昼夜节奏起搏器细胞中的哺乳动物血清反应因子的表达是否参与控制经验依赖性睡眠。最后，我将测试以下假设：昼夜节律细胞中突触终端数的经验依赖性增加是必需的。研究相关性：睡眠对于将新形成的记忆巩固到人类和果蝇中持久的持久关联中是必要的。鉴于人类和苍蝇的睡眠与可用于研究果蝇的遗传工具之间的相似之处，我建议将果蝇用作模型系统，以识别在新型社交体验后与睡眠相关的脑电路。我假设先前已确定为昼夜节律振荡器的细胞参与了经验依赖性睡眠的控制。