The Neuropsychology of Retrograde Amnesia

描述(由申请人提供)： 人类记忆功能障碍的一个显著特征是逆行性健忘症，指的是在健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按时间分级的。也就是说，与最近学到的信息相比，远程记忆(在记忆受损之前很久就学到的信息)通常是幸免于难的，或者受到的损害要小得多。人们认识到，对逆行性健忘症的研究可以揭示出关于正常长期记忆组织的大量信息。该提案要求支持三个概念上有关组织远程记忆的项目。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体功能与最近记忆和远程记忆提取的关系。这些项目代表了对远程记忆的严格评估，其结果将对有关记忆组织的理论产生重要影响。第一个项目1)《重新评估远距离情境恐惧记忆和海马体》将系统而严格地检验这一假说，即最近的情境恐惧记忆容易受到海马体损伤，而远距离情境恐惧记忆在海马体损伤后不受影响。所有的老鼠都会经历情境恐惧条件反射。皮损将在条件化后1天或100天发生。损伤的位置和范围将被操纵(完整的海马区病变、背侧海马区病变或腹侧海马区)。将使用两种不同的损伤方法(兴奋性毒性或热凝法)。第二个项目“远程空间记忆的组织”将评估空间记忆随着时间的推移进行重组的可能性，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个月将应用破坏性的LTP逆转药物输注程序。这一过程使海马体在保持测试期间保持不变，因此可以独立于表现来研究记忆。第三个项目“海马体、周围皮质和远程识别记忆”将评估海马体和周围皮质对最近和远程识别记忆的独立贡献--这是一种经常在人类、非人类灵长类动物和啮齿类动物身上研究的记忆形式。学习后1天或2个月将应用破坏性的LTP逆转药物输注程序。目标将是海马体的背侧和腹侧区域，或海马区周围皮质。

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.