Circadian Influences in Drosophila Memory Formation

昼夜节律对果蝇记忆形成的影响

• 批准号: 6668490
• 负责人: JERRY C YIN
• 金额: $ 16.6万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668490
• 关键词: Drosophilidae; apoptosis; behavior test; behavioral /social science research tag; behavioral genetics; biological models; calcium metabolism; circadian rhythms; developmental neurobiology; drug habituation; functional /structural genomics; gene induction /repression; gene interaction; gene mutation; genetic regulation; genetically modified animals; learning; memory; neural conduction; neural plasticity; time perception; transfection /expression vector

DESCRIPTION: (provided by applicant) Experience-dependent neural plasticity underlies all aspects of an animal's response to drugs of addiction. Whether the animal is undergoing initial responses to the drug, sensitization or habituation of that response, long-term addiction, or withdrawal, the neuronal and molecular mechanisms that are recruited are likely to be similar, if not identical, to those used during normal plasticity. Therefore, a complete understanding of molecules and physiological processes that influence learning and memory formation is likely to help elucidate the roles that these play in responses to drugs of abuse. This proposal focuses on the circadian system, and one particular "circadian" molecule, Per. Our Preliminary Results show that there are time of day effects on learning and memory formation, indicating that circadian factors affect these processes. In addition, genetic analysis shows that mutations in the per gene can either enhance or disrupt memory formation. Therefore, one of the main goals of this proposal is to determine if the central clock is important in the normal processes of learning and memory formation. To answer this question, novel, improved technology will be used to spatially and temporally regulate gene induction and cell ablation. Genetically inducible mosaic animals would be extremely useful for the analysis of any adult, neuronal function, including the anatomical dissection of drug responsiveness, learning and memory formation. In addition, a specific hypothesis, and its test, is proposed for the role of Per in various neuronal physiologies, including memory formation. This hypothesis, if true, may provide novel genetic tools and methodologies into fundamental problems of systems neuroscience, and opens up a new way to think about the cellular basis for plasticity and memory formation. Drosophila melanogaster is an excellent model organism for these studies. The universality of conserved molecules, cassettes of genes, and molecular mechanisms now extends from development to neuronal plasticity, learning, memory formation, circadian rhythms, sleep, neurodegenerative diseases and aging. The proposed work capitalizes on recent advances in genomic information, technological innovations and advances in the analyses of complex behavioral phenotypes in this system, and cannot be else whereat a reasonable pace or cost. Most critically, the work that is proposed would not have been conceptualized outside of the "critical mass" of information that exists for flies.

描述：（由申请人提供）经验依赖性的神经可塑性是动物对成瘾药物反应的各个方面的基础。无论该动物是对药物的初步反应，该反应，长期成瘾还是戒断的敏感性或习惯，被招募的神经元和分子机制都可能与正常可塑性期间使用的神经元和分子机制相似，即使不是相同。因此，对影响学习和记忆形成的分子和生理过程的完全理解可能有助于阐明这些作用在对滥用药物的反应中所扮演的角色。该提议侧重于昼夜节律系统，以及一个特定的“昼夜节律”分子。我们的初步结果表明，一天中有时间对学习和记忆形成影响，表明昼夜节律因素会影响这些过程。此外，遗传分析表明，每个基因的突变可以增强或破坏记忆形成。因此，该提案的主要目标之一是确定中心时钟在正常的学习和记忆形成过程中是否重要。为了回答这个问题，新颖的，改进的技术将用于在空间和时间上调节基因诱导和细胞消融。遗传诱导的摩西动物对于分析任何成年神经元功能的分析，包括药物反应性，学习和记忆形成的解剖学。此外，提出了特定的假设及其检验，即Per在各种神经元生理中的作用，包括记忆形成。该假设（如果为true）可能会为系统神经科学的基本问题提供新颖的遗传工具和方法，并为思考可塑性和记忆形成的细胞基础打开了一种新的方式。 果蝇Melanogaster是这些研究的出色模型生物。现在，保守分子，基因盒和分子机制的普遍性从发育延伸到神经元可塑性，学习，记忆形成，昼夜节律，睡眠，神经退行性疾病和衰老。拟议的工作利用了基因组信息的最新进展，技术创新以及该系统中复杂行为表型的分析的进步，并且不能是合理的速度或成本。最关键的是，提出的工作不会在存在的“临界质量”之外概念化。