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FUNCTIONAL ANALYSIS OF SLEEP HOMEOSTASIS IN DROSOPHILA

果蝇睡眠稳态的功能分析

基本信息

批准号：
10434653
负责人：
PAUL J SHAW
金额：
$ 34.45万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434653
关键词：
Ablation Address Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid beta-Protein Behavioral Genetics Biological Assay Biological Process Birth Brain Brain Injuries CREBBP gene Calcium Cells Choline phosphatase Coupled Data Defect Degenerative Disorder Development Dopamine Dopamine D1 Receptor Dopamine Receptor Drosophila genus Elements Exhibits Gene Targeting Genes Genetic study Genomics Goals Homeostasis Homologous Gene Human Image Impaired cognition Impairment Learning Length Lesion Lighting Maps Memory Memory impairment Metabolic Metabolic stress Microscopy Molecular Monitor Mushroom Bodies Neurodegenerative Disorders Neuroglia Neurons Oxidative Stress Pathology Pathway interactions Performance Production Property Proteins Receptor Signaling Role Serine Short-Term Memory Signal Transduction Sleep Sleep Architecture Time Variant biological adaptation to stress biological systems cell type experimental study fly knock-down loss of function nervous system disorder neuronal excitability overexpression prevent protective effect receptor expression response restoration serine racemase sleep physiology tau Proteins tool

项目摘要

Although the precise function of sleep remains unknown, there is little question that sleep is required for maintaining optimal performance in a large and diverse number of biological systems. Indeed, cognitive impairments associated with aging and neurodegenerative disorders are frequently accompanied by deficits in sleep physiology and architecture. We have previously shown that enhanced sleep can reverse memory deficits even in flies with catastrophic lesions to their primary memory center. We have now mapped a minimal circuitry required by this memory assay. Using genomics and behavioral genetics we have identified genes that can restore memory when they are modulated in a single circuit-component in a similar fashion as that produced by sleep. In this proposal we will determine the molecular pathways that regulate these genes. In addition, we will use calcium imaging to determine how restoring a single circuit component modulates the activity of other circuit components to restore memory during brain damage or the expression of Human Alzheimer's' related genes.

尽管睡眠的确切功能仍不清楚，但毫无疑问睡眠是维持大量不同数量的最佳表现所必需的生物系统。事实上，认知障碍与衰老和神经退行性疾病经常伴有睡眠生理缺陷和建筑。我们之前已经证明，增强睡眠可以逆转记忆即使果蝇的主要记忆中枢受到灾难性损伤，也会出现缺陷。我们有现在绘制了该内存分析所需的最小电路。利用基因组学和通过行为遗传学，我们已经鉴定出可以在记忆丧失时恢复记忆的基因以与睡眠产生的类似方式在单个电路组件中进行调制。在本提案中，我们将确定调节这些基因的分子途径。在此外，我们将使用钙成像来确定如何恢复单个电路组件调制其他电路组件的活动以恢复内存脑损伤或人类阿尔茨海默病相关基因的表达。