Sleep and Memory Formation in Drosophila

果蝇的睡眠和记忆形成

• 批准号: 7749318
• 负责人: JERRY C YIN
• 金额: $ 30.55万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7749318
• 关键词: Address; Affect; Age; Animals; Behavioral; Binding; Chemosensitization; Circadian Rhythms; Cognition; Cognitive; Cognitive deficits; Complex; Data; Diagnosis; Doxycycline; Drosophila genus; Event; Functional disorder; Future; Genes; Goals; Heat-Shock Response; Hour; Human; Huntington Disease; Impaired cognition; Learning; Link; Literature; Maintenance; Medical; Memory; Mental disorders; Metabolic; Molecular; Mus; Mutation; Nerve Degeneration; Neurobiology; Neurologic; Neurons; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phenotype; Play; Process; Property; RNA Interference; Reagent; Role; Sleep; Sleep Deprivation; Synapses; System; Temperature; Testing; Time; Training; Transgenes; Uncertainty; Work; base; depression; deprivation; fatty acid-binding proteins; fly; improved; interest; knock-down; long term memory; mouse model; neuronal patterning; neurophysiology; neurotransmission; overexpression; public health relevance; research study; sleep regulation; tool; transcription factor

DESCRIPTION (provided by applicant): Sleep and memory formation are both complex neurobiological "emergent" processes of considerable interest. The relationship between them has been a contentious issue-is sleep really necessary for memory formation (the sleep/memory hypothesis)? In this proposal, we will try to answer in a definitive manner this age-old question. Both of these processes are also commonly disrupted in neurological, neurodegenerative, and psychiatric dysfunctions. Whether "improving" one or the other can have broad-spectrum benefits is not clear. It is also unknown if enhancing one process will improve the other. This proposal has three broad parts. In the first, we have identified a gene that is involved in regulating sleep. Mild overexpression of this gene alters sleep, and enhances memory formation. Disrupting the gene has extreme effects on sleep. The tests (increase gene, test sleep and memory; disrupt gene, test sleep and memory) will be repeated using a second inducible system to validate current data. We will also use the gene to try to overcome sleep deprivation's harmful effects on memory formation. In the second part, we test the importance of particular "times of night" in memory formation. Finally, we test the functional and molecular interaction between a newly identified gene that interacts with our sleep-regulating gene. Taken together, this data should provide strong support for the sleep/memory hypothesis. This work has immediate medical impact, since almost all patients diagnosed with neurodegenerative and psychiatric diseases have sleep and cognitive problems. PUBLIC HEALTH RELEVANCE: Most, if not all, patients who suffer from neurodegenerative and psychiatric dysfunctions have problems with both sleep and cognition. Recently (Pallier et al. J Neurosci, 27, 7869-78, 2007), it was shown that a mouse model for Huntington's Disease has sleep and cognition problems. When these mice were treated for 4 weeks with a sleep-promoting drug, it partially reversed their cognitive deficits. This proposal addresses the problem of whether normal sleep contributes to memory formation. Eventually, this work will help identify pharmacological reagents that are countermeasures for sleep-related problems, cognitive deficits, and perhaps, both.

描述（由申请人提供）：睡眠和记忆形成都是相当兴趣的复杂神经生物学“新兴”过程。它们之间的关系是一个有争议的问题 - 记忆形成真正必要的睡眠（睡眠/记忆假设）？在此提案中，我们将尝试以确切的方式回答这个古老的问题。这两个过程在神经，神经退行性和精神病功能障碍中通常也会破坏。 “改善”一个或另一个是否可以具有广泛的福利，尚不清楚。还不知道增强一个过程是否会改善另一个过程。该提议有三个广泛的部分。首先，我们已经确定了一个参与调节睡眠的基因。该基因的轻度过表达改变了睡眠，并增强了记忆形成。破坏基因对睡眠具有极大的影响。测试（增加基因，测试睡眠和记忆力；破坏基因，测试睡眠和记忆）将使用第二个诱导系统重复以验证当前数据。我们还将使用该基因来克服睡眠剥夺对记忆形成的有害影响。在第二部分中，我们测试了特定“夜间”在记忆形成中的重要性。最后，我们在与睡眠调节基因相互作用的新鉴定的基因之间测试了功能和分子相互作用。综上所述，这些数据应为睡眠/记忆假设提供强有力的支持。这项工作立即产生医学影响，因为几乎所有被诊断为神经退行性和精神病患者的患者都有睡眠和认知问题。公共卫生相关性：大多数（如果不是全部）患有神经退行性和精神病性功能障碍的患者在睡眠和认知方面都有问题。最近（Pallier等人J Neurosci，27，7869-78，2007），显示出一种用于亨廷顿氏病的小鼠模型患有睡眠和认知问题。当这些小鼠用促进睡眠药物治疗4周时，它会部分逆转其认知缺陷。该建议解决了正常睡眠是否有助于记忆形成的问题。最终，这项工作将有助于确定药理学试剂，这些试剂是与睡眠有关的问题，认知缺陷以及两者的对策。