SYNAPTIC SUBSTRATES OF AGE-DEPENDENT MEMORY DEFICITS

年龄依赖性记忆缺陷的突触基质

• 批准号: 6615663
• 负责人: YURI GEINISMAN
• 金额: $ 35.84万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6615663
• 关键词: aging; animal age group; conditioning; electron microscopy; electrophysiology; hippocampus; histology; laboratory rat; memory disorders; neural transmission; neuroanatomy; neurobiology; neurons; short term memory; synapses

DESCRIPTION (Adapted from applicant's abstract): Loss of memory, especially for newly acquired information, is one of the hallmarks of normal aging. Yet, it has long been noted that some individuals retain remarkably intact memory even at advanced chronological age. An important and still unresolved problem in the neurobiology of aging is how to explain why memory is preserved in some aged individuals and lost or impaired in others. The proposed project is designed to investigate this problem by testing the hypothesis that memory deficits typical of the majority of aged individuals are due to a loss of synapses in pertinent brain regions. Young adult, middle-aged and old rats will be examined. A battery of behavioral tasks will be used to separate old rats into memory-impaired and memory-intact subgroups based on the presence or absence of memory deficits as compared with young adult and middle aged rats. The behavioral tasks to be employed include the Morris water maze, trace eyeblink conditioning and trace fear conditioning. The structural integrity of the hippocampus is a prerequisite for successful performance of animals on these tasks. Synapses will be analyzed in two hippocampal subregions, in the CA1 subfield and the dentate gyrus. Electrophysiologically, the efficacy of impulse transmission will be evaluated at Schaffer collateral-pyramidal cell synapses in the CA1 subregion and at medial perforant path-granule cell synapses in the dentate gyrus, using field potential recordings in vivo. At the electron microscopic level, unbiased techniques of moderm stereology will be employed to obtain estimates of the total number of synapses in the total volume of the CA1 stratum radiatum and the dentate middle molecular layer. Additionally, such techniques will also be used at the light microscopic level to make unbiased estimates of the total number of principal neurons in various hippocampal subregions. The results to be obtained will definitively demonstrate whether old animals with marked impairments of hippocampus-dependent memory function are the ones that exhibit a loss of hippocampal synapses and a decline in synaptic efficacy when compared with memory-intact old, middle-aged or young animals. These results will also show if a loss of hippocampal neurons occurs in memory-impaired old animals but not in memory-intact animals of different ages. Such data are important for a better understanding of the cellular mechanisms that underlie deficits in learning and memory typical of normal aging, as well as of memory disorders such as Alzheimer's disease. Moreover, the data may be useful for designing preventive measures to make aging "successful."

描述（改编自申请人摘要）：记忆丧失，尤其是 新获得的信息，是正常衰老的标志之一。却 人们早就注意到，有些人即使 年龄偏大一个重要的和尚未解决的问题， 衰老的神经生物学是如何解释为什么记忆在某些老年人中保留下来 在他人身上失去或受损。拟议的项目旨在 通过测试记忆缺陷典型的假设来研究这个问题， 大多数老年人的死亡是由于相关突触的丧失。 大脑区域。将检查青年、中年和老年大鼠。一 一系列的行为任务将被用来将老年大鼠分为 记忆受损和记忆完整的亚组，基于是否存在 与年轻成年和中年大鼠相比，记忆缺陷。的 采用的行为任务包括Morris水迷宫、跟踪眨眼 条件反射和微量恐惧条件反射。的结构完整性 海马体是动物在这些方面成功表现的先决条件。 任务突触将在两个海马亚区进行分析，在CA 1 subfield和齿状回。电生理学，冲动的功效 将在Schaffer侧支-锥体细胞突触处评价传递 在CA 1亚区和内侧穿支-颗粒细胞突触中， 齿状回，在体内使用场电位记录。在电子 微观水平，现代体视学的无偏技术将被用来 获得CA 1总体积中突触总数的估计值 放射层和齿状中分子层。此外，这种 技术也将用于在光显微镜水平，使公正的 不同海马区主要神经元总数的估计 分区域.获得的结果将明确表明， 具有明显的海马依赖性记忆功能障碍的老年动物 是那些表现出海马突触缺失和 与记忆完整的老年人、中年人或年轻人相比， 动物这些结果也将显示海马神经元的损失是否发生 在记忆力受损的老年动物中，但在记忆力完好的不同动物中， 年龄这些数据对于更好地理解细胞内的 正常人的学习和记忆缺陷的基础机制 衰老，以及记忆障碍，如阿尔茨海默氏病。此外，委员会认为， 这些数据可能有助于设计预防措施， “成功。"