SYNAPTIC SUBSTRATES OF AGE-DEPENDENT MEMORY DEFICITS

年龄依赖性记忆缺陷的突触基质

• 批准号: 6169472
• 负责人: YURI GEINISMAN
• 金额: $ 33.33万
• 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/6169472
• 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(改编自申请人的摘要)：失忆，尤其是 新获得的信息，是正常衰老的标志之一。然而，它 很早就注意到，有些人甚至保持着非常完好的记忆力 在年龄较高的时候。一个重要但仍未解决的问题 衰老的神经生物学是如何解释为什么某些老年人的记忆会被保留 个人和他人的遗失或受损。拟议的项目旨在 通过检验以下假设来研究这个问题：记忆缺陷通常是 大多数老年人是由于相关的突触丢失所致 大脑区域。对幼年、中年和老年大鼠进行检查。一个 一组行为任务将被用来将老年大鼠分成 基于存在或不存在记忆受损和记忆完好的亚组 与青壮年大鼠和中年大鼠相比，记忆缺陷。这个 将使用的行为任务包括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。将分析CA1区海马区的两个亚区的突触 亚野和齿状回。电生理学上，脉冲的功效 传输将在Schaffer侧支-锥体细胞突触进行评估 在CA1亚区和内侧穿通径-颗粒细胞突触 齿状回，使用活体中的场电位记录。在电子 在微观层面，现代体视学的无偏见技术将被应用于 获得对CA1总体积中突触总数的估计 放射层和齿状中分子层。此外，这样的 还将在光学显微镜水平上使用技术，以使 不同海马区主神经元总数的估计 子区域。将获得的结果将最终证明 海马区依赖记忆功能明显受损的老年动物 是那些表现出海马区突触丢失和脑内 与记忆完好的老年人、中年人或年轻人的突触疗效比较 动物。这些结果还将表明，如果海马神经元发生丢失 在记忆受损的老年动物中，但在记忆完好的不同种类的动物中 年龄。这些数据对于更好地理解细胞 导致正常学习和记忆缺陷的机制 衰老，以及阿尔茨海默病等记忆障碍。此外， 这些数据可能有助于设计预防衰老的措施 “成功了。”