DIFFUSIBLE MESSENGERS IN LONG TERM POTENTIATION

这项研究计划的主要目标是了解 基本的细胞和生化机制， 增强（LTP）的大脑兴奋性突触传递。 LTP是一个 神经活动依赖性突触增强的形式，已成为一种 哺乳动物记忆储存细胞机制的主要模型 中枢神经系统（CNS）。 LTP是由位于 突触的突触后侧，并表达，至少部分，通过改变 在突触前末梢 有证据表明，一个信号，所以- 称为逆行信使，从突触后传递到 突触的突触前侧以诱导LTP。 这个的身份 信使是有争议的，但领先的候选人是一氧化氮（NO）。 本研究将着重探讨NO和其他潜在的扩散性物质在 逆行信使在产生LTP，使用大鼠海马脑片作为 实验系统。 实验将使用一系列 电生理技术。 具体来说，我们的目标是阐明三个方面的扩散信使 在LTP中的作用 首先，我们将研究激活的过程， 否，特别强调确定这些是否位于 突触前末梢 第二，我们将研究能够 将LTP从受刺激的突触传递到未受刺激的突触。 这 所谓的分布式增强似乎依赖于一个可扩散的 最后，我们将比较NO和非NO。 海马CA 1区的lTP依赖形式作为一种方式 确定NO在LTP中发挥的独特作用。

The broad objective of this research plan is to gain knowledge of the fundamental cellular and biochemical mechanisms underlying long-term potentiation (LTP) of brain excitatory synaptic transmission. LTP is a form of neural activity-dependent synaptic enhancement that has become a leading model for a cellular mechanism of memory storage in the mammalian central nervous system (CNS). LTP is induced by processes residing in the postsynaptic side of synapses, and expressed, at least in part, by changes in the presynaptic terminal. Evidence has mounted that a signal, the so- called retrograde messenger, passes from the postsynaptic to the presynaptic side of the synapse to induce LTP. The identity of this messenger is controversial, but the leading candidate is nitric oxide (NO). This study will focus on the role of NO and other potential diffusible retrograde messengers in producing LTP, using the rat hippocampal slice as the experimental system. Experiments will be conducted using a range of electrophysiological techniques. Specifically, we aim to elucidate three aspects of diffusible messenger function in LTP. First, we will study the processes that are activated by NO, with a particular emphasis on determining if these reside in the presynaptic terminal. Second, we will study the process that can communicate LTP from stimulated synapses to non-stimulated synapses. This co-called distributed potentiation appears to rely on a diffusible messenger and depends on NO. Finally, we will compare NO and non-NO- dependent forms of lTP in the CA1 region of the hippocampus as a way of determining the unique role that NO plays in LTP.