AGING, MEMORY AND SEPTOHIPPOCAMPAL FUNCTION

衰老、记忆和七海马功能

• 批准号: 3121983
• 负责人: DAVID S OLTON
• 金额: $ 11.51万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3121983
• 关键词: acetylcholine; aging; anticholinergic agent; behavior test; bicuculline; brain electrical activity; brain septal area; cholinergic agents; electroencephalography; gamma aminobutyrate; hippocampus; laboratory rat; memory; microinjections; molecular psychobiology; muscimol; neural information processing; picrotoxin; scopolamine

The long-term objective of this project is to understand the relation among recent memory, septohippocampal function, and aging. Normal aging and age-related neurodegenerative diseases can both produce impairments of memory. Understanding the neural mechanisms related to these memory impairments, and attempting to alleviate them through neural manipulations, can have a significant impact on the quality of life of the aged population. This project has three specific goals. (1) Determine the extent to which direct microinfusion of substances into the medial septal area (MSA) of rats can improve mnemonic function in aged rats with impaired memory, and examine the correlations among mnemonic improvements, hippocampal electrophysiology as measured by theta, and cholinergic stimulation as measured by hemicholinium-3 (HC-3) binding. (2) Determine the extent to which aging changes the sensitivity of the septohippocampal system to disruption by compounds directly infused into the MSA, producing shifts of the dose-response curve relating the dose of these compounds to the magnitude of the memory impairment. (3) Examine the individual differences in aged populations with respect to the magnitude of the memory impairment, sensitivity to MSA infusions, and activity of the cholinergic system as examined by HC-3 binding. The experimental design tests rats of 4 different ages in two tasks to assess recent memory. Compounds infused into the MSA are designed to stimulate and inhibit, respectively the cholinergic system (scopolamine, oxotremorine) and the GABAergic system (picrotoxin, bicuculline, muscimol). Theta is recorded from the hippocampus to indicate the electrophysiological effects of these compounds. HC-3 is measured to determine the extent to which cholinergic system is affected.

本项目的长期目标是了解 近期记忆隔海马功能和衰老之间的关系 正常老化 和与年龄有关的神经退行性疾病都能导致 记忆。 了解与这些记忆相关的神经机制 并试图通过神经网络来缓解这些障碍 操作，可以对生活质量产生重大影响， 老年人口。 该项目有三个具体目标。（一） 确定直接微量输注物质进入 内侧隔区（MSA）能改善大鼠的记忆功能， 老年大鼠记忆力受损，并检查之间的相关性 记忆改善，海马电生理学， 和胆碱能刺激，如通过半胆碱-3（HC-3）测量的 约束力(2)确定老化改变灵敏度的程度 的隔海马系统的破坏的化合物直接 输注到MSA中，产生剂量-反应曲线的移动 将这些化合物的剂量与记忆的大小联系起来， 损伤(3)研究老年人群的个体差异 关于记忆损伤的程度，对 MSA输注和胆碱能系统的活性，通过 HC-3结合。 实验设计在两个任务中测试4个不同年龄的大鼠， 评估最近的记忆 注入MSA的化合物旨在 分别刺激和抑制胆碱能系统（东莨菪碱， 氧化震颤素）和GABA能系统（印防己毒素，荷包牡丹碱， 蝇蕈醇）。 θ是从海马体记录的， 这些化合物的电生理效应。 HC-3被测量为 确定胆碱能系统受到影响的程度。