DIFFUSIBLE MESSENGERS IN LONG TERM POTENTIATION

这项研究计划的总体目标是了解 长期致病的基本细胞和生化机制 脑兴奋性突触传递的增强(LTP)LTP是一种 一种依赖神经活动的突触增强形式，已成为 哺乳动物记忆存储细胞机制的领先模型 中枢神经系统(CNS)。LTP由驻留在 突触的突触后侧，并至少部分通过变化表达 在突触前终末。越来越多的证据表明，有一个信号，所以- 被称为逆行信使，从突触后传递到 突触前侧的突触，以诱导LTP。这件事的身份 Messenger备受争议，但领先的候选者是一氧化氮(NO)。 这项研究将集中在NO和其他潜在的可扩散的作用上 大鼠海马片LTP产生过程中的逆行信使 实验系统。实验将使用一系列 电生理技术。 具体地说，我们的目标是阐明可扩散信使的三个方面 在LTP中的功能。首先，我们将研究由 否，特别强调确定这些是否驻留在 突触前终末。第二，我们将研究能够 将LTP从受刺激的突触传递到非刺激的突触。这 所谓的分布式增强似乎依赖于可扩散的 Messenger，并依赖于No.最后，我们将比较NO和Non-No- LTP在海马CA1区的依赖形式作为一种 确定NO在LTP中所起的独特作用。

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.