Spatial- Temporal Aspects of Drosophila Memory Formation

果蝇记忆形成的时空方面

• 批准号: 7050211
• 负责人: JERRY C YIN
• 金额: $ 31.97万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-08 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7050211
• 关键词: Drosophilidae; anesthesia; behavior test; behavioral /social science research tag; biological models; conditioning; gene expression; gene induction /repression; heat shock proteins; learning; long term memory; memory; neuroanatomy; protein isoforms; protein structure function; tetracyclines; transfection

DESCRIPTION (provided by applicant): Since the dawn of language, one of the most intriguing questions has been the physical location of human memories in the brain. Neurologists have inferred anatomical function from studies of injury and disease to different areas of the brain. Experimental psychologists have used brain lesion as a tool to dissect function in experimental animals. We propose to use genetic tools to address this question in the common fruit fly, Drosophila melanogaster. This genetically tractable, genome-mined and experimentally pliable model organism exhibits complex neuronal functions such as learning and memory formation, circadian biology, sleep, and stereotyped behavioral responses to addictive drugs. Because of the rich history of genetics in this animal, the total access to the genome structure and information-coding capacity, and the variety of molecular tools that can be applied, it is likely that we will achieve a complete, multilevel understanding of complex neuronal function in this organism. There are two types of consolidated memory that exists for an olfactory-avoidance behavior in Drosophila, anesthesia-resistant memory (ARM) and long-term memory (LTM). We have disrupted and enhanced both of these processes through the reverse genetic manipulation of single genes. In parallel, we have developed new technology that allows both spatial (anatomical) and temporal control over the induction of transgenes. In this proposal, we will utilize this technology to conditionally express genes that inhibit each of these types of memory. Because we can control the brain regions where the disrupting genes are expressed, it will be possible to anatomically dissect these memories. This information will provide a first-glimpse of what a memory looks like in the three-dimensional space of the brain. In mammals, there are some very intriguing temporal properties of memory formation, suggesting that memory "consolidation" is not necessarily a process with a fixed starting and ending point in time. Since we can also control when the interfering genes are induced, we will analyze temporal questions about memory formation. These experiments should help us understand the complexity of memory formation and its relationship with on-going neuronal processes. Finally, we will test the feasibility of using the spatialtemporal system to ablate adult brain neurons, providing a totally complementary approach to many of the same issues.

描述（由申请人提供）：自从语言黎明以来，最有趣的问题之一是人类记忆在大脑中的物理位置。神经科医生从损伤和疾病研究到大脑的不同区域推断出解剖功能。实验心理学家已使用脑病变作为剖析实验动物功能的工具。我们建议使用遗传工具在共同的果蝇果蝇中解决这个问题。这种具有遗传障碍，基因组开采和实验性柔韧模型的生物具有复杂的神经元功能，例如学习和记忆形成，昼夜节律生物学，睡眠和对成瘾药物的刻板行为反应。由于这种动物中遗传学的悠久历史，可以全面访问基因组结构和信息编码能力，以及可以应用的各种分子工具，因此我们很可能会在该生物体中获得对复杂神经元功能的完整，多层次的理解。在果蝇，抗麻醉记忆（ARM）和长期记忆（LTM）中，存在两种类型的合并记忆。我们通过单个基因的反向遗传操纵来破坏和增强这两个过程。同时，我们开发了新技术，可以使空间（解剖学）和对转基因诱导的时间控制。在此提案中，我们将利用这项技术来表达抑制这些类型记忆中每一种的基因。因为我们可以控制表达破坏基因的大脑区域，因此可以解剖学剖析这些记忆。这些信息将提供第一张兴奋剂，说明大脑三维空间中的记忆是什么样的。在哺乳动物中，有一些非常有趣的记忆形成时间特性，这表明内存“合并”不一定是一个具有固定的起始和终点的过程。由于我们还可以控制何时诱导干扰基因，因此我们将分析有关记忆形成的时间问题。这些实验应有助于我们了解记忆形成的复杂性及其与持续的神经元过程的关系。最后，我们将测试使用时空系统消融成人脑神经元的可行性，为许多相同问题提供一种完全互补的方法。