Mechanisms of Long-Term Memory Maintenance in Aplysia.

海兔的长期记忆维持机制。

• 批准号: 8843545
• 负责人: DAVID L GLANZMAN
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843545
• 关键词: Address; Affect; Afferent Neurons; Alzheimer' s Disease; Aplysia; Attention; Behavioral; Belief; Biological; Biological Models; Brain; Brain Diseases; Catalytic Domain; Cell Culture Techniques; Cell physiology; Cells; Cues; Data; Development; Diabetes Mellitus; Disease; Dominant-Negative Mutation; Electroconvulsive Shock; Exhibits; Experimental Models; Explosion; Exposure to; Goals; Individual; Invertebrates; Knowledge; Learning; Maintenance; Marines; Mediating; Memory; Memory Loss; Mental Depression; Molecular; Morphology; Motor Neurons; Neurons; Organism; Patients; Phosphotransferases; Physiologic pulse; Population; Post-Traumatic Stress Disorders; Property; Protein Isoforms; Protein Kinase; Protein Kinase C; Protein Synthesis Inhibition; Protein Synthesis Inhibitors; Reflex action; Reporting; Retrieval; Role; Serotonin; Snails; Staging; Stimulus; Synapses; Synaptic Transmission; Synaptic plasticity; System; Techniques; Testing; Ubiquitin; Uncertainty; United States; Withdrawal; Woman; atypical protein kinase C; effective therapy; experience; fluidity; long term memory; memory consolidation; men; multicatalytic endopeptidase complex; neurobiological mechanism; overexpression; postsynaptic; presynaptic; prevent; stem; therapy development

DESCRIPTION (provided by applicant): A significant percentage of people in the US have disorders of long-term memory; among these are people suffering from Alzheimer's disease (AD), posttraumatic stress disorder (PTSD), diabetes and depression. In addition to problems forming new memories, patients suffering from these diseases can have difficulty accessing older memories, especially in the advanced stages of the diseases, or-in the case of PTSD-patients may have difficulty regulating traumatic long-term memories. An important, and at present unresolved, question is the extent to which the memory difficulties experienced by some patients stem from retrieval problems or to degradation of the physical memory traces themselves. In order to answer this question, neuroscientists must learn more about how the brain maintains long-term memories. Contrary to long-held beliefs, older memories are not stable, even in healthy individuals, but, under some circumstances, can be rendered strikingly labile. Furthermore, once in this labile state the memories can become permanently disrupted. Two phenomena of long-term memory, termed memory reconsolidation and memory erasure, have attracted particular attention in this regard. Memory reconsolidation refers to the finding that, after having been given a reminder cue for a previously learned experience, a previously consolidated memory of that experience can become disrupted by treatments, such as exposure to inhibitors of protein synthesis, that interfere with original memory consolidation. So- called memory erasure has been observed following inhibition of a specific isoform of protein kinase C (PKC), known as PKM¿. PKM¿ contains the catalytic domain of an atypical PKC, but lacks the regulatory domain and is therefore constitutively active. This property, it has been proposed, endows PKM¿ with the capacity mediate memory maintenance. The phenomena of memory reconsolidation and memory erasure remain poorly understood and controversial. In part, these problems stem from the enormous complexity of the mammalian brain, as well as the complexity of the forms of memory that have been examined in studies of reconsolidation and memory erasure. This project will develop a simple model experimental system for a reductionist analysis of memory reconsolidation and memory erasure. The focus of the project will be on a nonassociative form of learning, long-term sensitization (LTS), in the marine snail, Aplysia. This organism offers several major advantages for the study of long-term memory maintenance, including the ability to investigate a form of long-term (>24 hr) synaptic plasticity, known as long-term facilitation, that unambiguously mediates the learning. The PI will use behavioral, cellular and molecular techniques to determine the neurobiological mechanisms that underlie memory reconsolidation and memory erasure. Data from the proposed studies will facilitate the development of treatments for disorders of long-term memory, including AD and PTSD.

描述（由适用提供）：美国很大一部分人患有长期记忆的障碍；其中包括患有阿尔茨海默氏病（AD），创伤后应激障碍（PTSD），糖尿病和抑郁症的人。除了形成新记忆的问题外，患有这些疾病的患者可能很难获得较旧的记忆，尤其是在疾病的高级阶段，或者在PTSD患者的情况下可能会有困难的创伤性长期记忆。一个重要的，目前尚未解决的问题是某些患者遇到的记忆困难在多大程度上是由于检索问题或物理记忆本身降解的程度。为了回答这个问题，神经科学家必须了解更多有关大脑如何保持长期记忆的信息。与长期以来的信念相反，即使在健康的个体中，较旧的记忆也不稳定，但是在某些情况下，可以标记出惊人的标签。此外，一旦在这种不稳定的状态中，记忆就会永久破坏。在这方面引起了两个长期记忆的现象，称为记忆重新整合和记忆擦除，引起了人们的特别关注。记忆重新整合是指以下发现，即在提醒先前学到的经验提醒提醒后，先前对这种经验的合并记忆可能会因治疗而破坏，例如暴露于蛋白质合成的抑制剂，即干扰原始记忆的巩固。所以- 在抑制特定的蛋白激酶C（PKC）（称为pKM pkm的）的同工型后，已经观察到称为记忆擦除。 PKM含有非典型PKC的催化结构域，但缺乏调节域，因此具有组成性活性。已经提出了该属性，它赋予了PKM“容量中值存储器的维护。记忆重新溶解和记忆擦除的现象仍然很广泛且引起争议。在某种程度上，这些问题源于哺乳动物大脑的复杂性增强，以及在重新溶解和记忆擦除研究中已研究的记忆形式的复杂性。该项目将开发一个简单的模型实验系统，以简化记忆重新溶解和记忆擦除的分析。该项目的重点将放在海洋蜗牛，高脂的非缔合性学习，长期敏感性（LTS）的形式上。该生物体为研究长期记忆维持提供了几个主要优势，包括研究长期（> 24小时）突触可塑性形式的能力， 被称为长期设施，它明确地介导了学习。 PI将使用行为，细胞和分子技术来确定记忆重新溶解和记忆擦除的神经生物学机制。拟议研究的数据将支持开发长期记忆障碍的治疗方法，包括AD和PTSD。