COMPONENTS OF HIPPOCAMPAL SYNAPTIC PLASTICITY

记忆功能障碍是最早和最衰弱的特征之一 老年痴呆症（AD）最终改善或逆转记忆 功能障碍，并了解为什么它是如此突出地参与AD， 将是更好地理解记忆机制所必需的。长- 时程增强（LTP）是突触可塑性的一种使用依赖性形式 作为记忆存储的细胞基础的一部分，这是非常有趣的。 这是突触功效的持续增加。作为确定 其基本机制，该项目的目标是测试 假设LTP不是一个单一的过程，而是由4个不同的过程组成， 件.其组成部分的确定将在 未来通过进一步研究每个组件的机制， 以及它们如何通过衰老和AD改变。细胞外和 将从大鼠的CA 1区进行全细胞膜片钳记录 海马切片制备。 短时程增强（STP）是突触功效的增加， 大约15分钟后恢复到基线。它被认为是 一种由阈下刺激引起的LTP递减形式。初步 然而，数据表明，STP可能是一个单独表达的组成部分， 可塑性具体目标1是检验STP是一种 通过比较，从LTP中分离但相关的增强成分 重叠区域STP和LTP诱导和表达的五个步骤 和差异。 几种类型的实验表明，LTP可能包括早期 （< 1/2- 2 hrs）和晚期阶段。初步数据表明，早期LTP 表达改变成对脉冲易化（PPF），这是一种突触前形式， 增强，表明早期LTP表达包括 突触前位点具体目标2是使用PPF来检验假设 持续的LTP由两部分组成：早期的第二信使， 介导的突触前成分和晚期突触后成分。 长时程抑制（LTD）是突触效能的持续降低 这可能会扩展学习能力或导致遗忘。其 潜在的机制可能只是LTP的逆转，也可能是一种 突触可塑性的独立成分。初步数据显示， LTD增加PPF，表明其表达位点，如LTP， 包括突触前部位具体目标3是检验假设 LTP和LTD是突触可塑性的两个独立成分， 研究它们之间的两种相互作用，以及它们对PPF的影响。 如果LTP由几个组成部分组成，则必须确定 因为每一个都可能提供独特的网站， 突触可塑性和记忆的治疗干预。

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.