The Neuropsychology of Retrograde Amnesia

逆行性遗忘症的神经心理学

• 批准号: 8140379
• 负责人: Robert E Clark
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8140379
• 关键词: Address; Age; Age-associated memory impairment; Alzheimer' s Disease; American; Amnesia; Animal Experimentation; Animals; Attention; Basic Science; Behavioral; Behavioral Paradigm; Benchmarking; Biological Models; Brain; Dorsal; Elderly; Electrocoagulation; Evaluation; Financial cost; Fright; Functional disorder; Healthcare Systems; Hippocampus (Brain); Human; Impairment; Incidence; Infusion procedures; Injection of therapeutic agent; Laboratories; Learning; Left; Lesion; Link; Location; Medial; Memory; Memory Loss; Memory impairment; Methods; Mission; Neuropsychology; Operative Surgical Procedures; Paper; Performance; Pharmaceutical Preparations; Population; Procedures; Publications; Publishing; Pump; Rattus; Relative (related person); Reporting; Request for Proposals; Research; Retrieval; Retrograde Memory Losses; Retrograde amnesia; Risk Factors; Rodent; Science; Series; Structure; Temporal Lobe; Testing; Time; Training; Veterans; Water; Work; classical conditioning; combat; conditioned fear; conditioning; experience; long term memory; memory process; memory recognition; memory retention; nonhuman primate; novel; object recognition; prevent; radiofrequency; relating to nervous system; theories; trend

DESCRIPTION (provided by applicant): A prominent feature of human memory dysfunction is retrograde amnesia, which refers to a loss of memories that were acquired before the onset of amnesia. In humans retrograde memory loss is often temporally graded. That is, remote memory (information learned long before the onset of memory impairment) is often spared, or much less impaired, relative to information learned recently. It is recognized that the study of retrograde amnesia can reveal an enormous amount about the organization of normal long-term memory. The proposal requests support for three, conceptually related projects concerning the organization of remote memory. All three projects will examine the relationship of hippocampal function to the retrieval of recent memory and remote memory using rats as the model system and sophisticated, modern experimental methods. These projects represent a rigorous evaluation of remote memory and the results will be important for theories concerning the organization of memory. The first project 1) "Reevaluating Remote Context Fear Memory and the Hippocampus" will systematically and rigorously test the hypothesis that recent context fear memory is vulnerable to hippocampal damage, but remote context fear memory is spared following hippocampal damage. All rats will undergo context fear conditioning. The lesions will be made 1 day or 100 days after conditioning. The location and extent of the lesions will be manipulated (full hippocampal lesions, dorsal hippocampal lesions, or ventral hippocampal). Two different lesions methods will be used (excitotoxic or thermocoagulation). The second project 2) "The Organization of Remote Spatial Memory" will evaluate the possibility that spatial memory reorganizes over time, like other forms of nonspatial memory, but that the hippocampus is always required for the behavioral expression of spatial memory. A disruptive, LTP reversing drug infusion procedure will be applied 1 day or 2 months after learning. This procedure leaves the hippocampus intact during the retention test so memory can be studied independent of performance. The third project 3) "The Hippocampus, Perirhinal Cortex, and Remote Recognition memory" will evaluate the independent contributions the hippocampus and perirhinal cortex make to both recent and remote recognition memory-a form of memory that is frequently studied in humans, non-human primates, and rodents. A disruptive, LTP reversing drug infusion procedure will be applied 1 day or 2 months after learning. The dorsal and ventral regions of the hippocampus, or the perirhinal cortex will be targeted. PUBLIC HEALTH RELEVANCE: By the age of 70 years, 60% of the population will experience significant memory related problems including Alzheimer's (30%) and Benign Senescent Forgetfulness (30%). If current trends continue, by the year 2050, 14 million older Americans are expected to have AD. Given that close to 40% of the population served by the VA is elderly and age is the greatest risk factor for AD and other memory problems, the increasing incidence of memory related problems in veteran's healthcare systems will significantly impact the VA's mission. One of the most fundamental questions in brain science is how the brain stores and reorganizes memory over time. Basic research on memory processes and identifying the neural structures involved in memory storage are critical steps for developing treatments to ameliorate or prevent memory problems and to combat the personal and financial cost of memory loss.

描述（由申请人提供）： 人类记忆功能障碍的一个突出特征是逆行性遗忘症，这是指在遗忘症发作之前获得的记忆的丧失。在人类中，逆行性记忆丧失通常是暂时分级的。也就是说，相对于最近学到的信息，远程记忆（早在记忆障碍发生之前学到的信息）通常不会受到影响，或者受到的损害要小得多。人们认识到，对逆行性遗忘症的研究可以揭示大量关于正常长期记忆组织的信息。该提案要求支持三个概念上相关的关于远程记忆组织的项目。所有这三个项目都将使用大鼠作为模型系统和先进的现代实验方法来研究海马功能与最近记忆和远程记忆检索的关系。这些项目代表了对远程记忆的严格评估，其结果对记忆组织理论具有重要意义。第一个项目1）“重新评估远程背景恐惧记忆和海马”将系统和严格地测试假设，即最近的背景恐惧记忆容易受到海马损伤，但远程背景恐惧记忆在海马损伤后幸免。所有大鼠都将经历情境恐惧条件反射。将在处理后1天或100天进行损伤。将操作病变的位置和范围（全海马病变、背侧海马病变或腹侧海马）。将使用两种不同的损伤方法（兴奋性毒性或热凝）。第二个项目2）“远程空间记忆的组织”将评估空间记忆随着时间的推移而重组的可能性，就像其他形式的非空间记忆一样，但海马体总是需要空间记忆的行为表达。学习后1天或2个月将应用破坏性LTP逆转药物输注程序。这个过程在保持测试期间使海马体保持完整，因此可以独立于表现来研究记忆。第三个项目3）“海马，嗅周皮层和远程识别记忆”将评估海马和嗅周皮层对最近和远程识别记忆的独立贡献-一种经常在人类，非人类灵长类动物和啮齿动物中研究的记忆形式。学习后1天或2个月将应用破坏性LTP逆转药物输注程序。海马体的背侧和腹侧区域或嗅周皮质将被靶向。 公共卫生相关性： 到70岁时，60%的人口将经历重大的记忆相关问题，包括阿尔茨海默氏症（30%）和良性衰老健忘症（30%）。如果目前的趋势继续下去，到2050年，预计将有1400万美国老年人患有AD。鉴于VA服务的人口中有近40%是老年人，年龄是AD和其他记忆问题的最大风险因素，退伍军人医疗保健系统中记忆相关问题的发病率不断增加将显著影响VA的使命。脑科学中最基本的问题之一是大脑如何随着时间的推移存储和重组记忆。对记忆过程的基础研究和识别参与记忆存储的神经结构是开发治疗方法以改善或预防记忆问题以及对抗记忆丧失的个人和经济成本的关键步骤。