COMPONENTS OF HIPPOCAMPAL SYNAPTIC PLASTICITY

海马突触可塑性的组成部分

• 批准号: 2431216
• 负责人: PAUL E SCHULZ
• 金额: $ 10.26万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2431216
• 关键词: NMDA receptors; bicuculline; calcium flux; electrostimulus; enzyme activity; excitatory aminoacid; extracellular; hippocampus; laboratory rat; long term potentiation; microelectrodes; nerve threshold; neural facilitation; neural plasticity; neuropharmacology; nifedipine; picrotoxin; protein kinase A; synapses; voltage /patch clamp; voltage gated channel

Memory dysfunction is one of the earliest and most debilitating features of Alzheimer's disease (AD). To eventually improve or reverse memory dysfunction, and to understand why it is so prominently involved in AD, it will be necessary to better understand mechanisms underlying memory. Long- term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as part of the cellular basis of memory storage. It is a sustained increase in synaptic efficacy. As a step in identifying its underlying mechanisms, the goal of this project is to test the hypothesis that LTP is not a unitary process, but consists of 4 distinct components. Identification of its components will be followed in the future by further study of the mechanisms underlying each component, as well as how they may be altered by aging and in AD. Extracellular and whole-cell patch clamp recordings will be made from area CA1 in the rat hippocampal slice preparation. Short-term potentiation (STP) is an increase in synaptic efficacy that returns to baseline in approximately 15 minutes. It has been assumed to be a decremental form of LTP induced by subthreshold stimulation. Preliminary data, however, suggest that STP may be a separately expressed component of plasticity. Specific Aim 1 is to test the hypothesis that STP is a separate, but related, component of potentiation from LTP by comparing five steps in STP and LTP induction and expression for areas of overlap and difference. Several types of experiments have suggested that LTP may consist of early (< 1/2-2hrs) and late phases. Preliminary data suggests that early LTP expression alters paired-pulse facilitation (PPF), a presynaptic form of potentiation, suggesting that early LTP expression includes the presynaptic locus. Specific Aim 2 is to use PPF to test the hypothesis that sustained LTP consists of two components: an early, second messenger mediated, presynaptic component, and a late postsynaptic component. Long-term depression (LTD) is a sustained decrease in synaptic efficacy that may extend the capacity for learning or underlie forgetting. Its underlying mechanism may simply be a reversal of LTP, or it may be a separate component of synaptic plasticity. Preliminary data suggest that LTD increases PPF suggesting that its loci of expression, like LTP, includes the presynaptic site. Specific Aim 3 is to test the hypothesis that LTP and LTD are two independent components of synaptic plasticity by examining two interactions between them, and their effects on PPF. If LTP consists of several components, it would be important to identify and characterize them because each might provide unique sites for therapeutic intervention in synaptic plasticity and memory.

记忆功能障碍是最早，最令人衰弱的功能之一 阿尔茨海默氏病（AD）。最终改善或反向内存 功能障碍，并了解为什么它如此突出参与广告 为了更好地理解内存的机制是必要的。长的- 术语增强（LTP）是一种使用的突触可塑性形式 作为存储器存储的蜂窝基础的一部分，这引起了人们的极大兴趣。 这是突触功效的持续增加。作为识别的一步 它的基本机制，该项目的目的是测试 假设LTP不是一个统一的过程，而是由4个不同的 成分。将遵循其组件的识别 通过进一步研究每个组件的基础机制， 以及如何通过衰老和AD改变它们。细胞外和 全细胞贴片夹记录将由大鼠区域CA1进行 海马切片准备。 短期增强（STP）是突触功效的提高 大约15分钟内返回基线。被认为是 亚阈值刺激引起的LTP的降低形式。初步的 但是，数据表明STP可能是单独表达的组成部分 可塑性。具体目的1是测试STP是一个假设 通过比较LTP分开但相关的功能的组成部分 重叠区域的STP和LTP诱导和表达五个步骤 和差异。 几种类型的实验表明LTP可能由早期组成 （<1/2-2小时）和晚期。初步数据表明早期LTP 表达变化配对脉冲促进（PPF），一种突触前的形式 增强，表明早期LTP表达包括 突触前基因座。具体目标2是使用PPF检验假设 持续的LTP由两个组成部分组成：早期，第二使者 介导的，突触前成分和后突触后成分。 长期抑郁（LTD）是突触功效的持续降低 这可能会扩大学习或遗忘的能力。它是 基本机制可能只是LTP的逆转，也可能是 突触可塑性的单独组成部分。初步数据表明 LTD增加了PPF，表明其表达基因座，例如LTP， 包括突触前部位。特定目的3是检验假设 该LTP和LTD是两个独立的突触可塑性组成部分 检查它们之间的两个相互作用及其对PPF的影响。 如果LTP由几个组件组成，则必须确定 并将它们特征为特征，因为每个人都可以提供独特的网站 突触可塑性和记忆的治疗干预。