BIOCHEMICAL MECHANISMS FOR LONG-TERM POTENTIATION

海马区突触传递的长时程增强 是一个特征良好、易于处理的模型系统，用于研究 哺乳动物的学习和记忆。不仅有各种各样的证据 支持LTP在内存获取中的作用，离散的、紧凑的 海马体的结构允许方便地监测 电生理反应，和相对容易的体外 操纵。海马区脑片制备技术的研究进展 研究LTP的手段提供了一个研究分子的系统 以及这种效应的生物物理基础。在这篇文章中描述的研究 应用的重点是维持的分子机制 LTP在大鼠海马区CA1区的表达。使用各种不同的 生化和药理学的方法和途径，我们将 探讨蛋白激酶C在维持性心肌梗死中的作用 LTP。具体而言，这些研究将涉及以下问题： 蛋白激酶C在体内持续激活的机制是什么？ NMDA受体依赖性LTP的维持期？执着是怎么回事 去增强刺激能逆转PKC的激活吗？这些研究 将作为未来研究探索更大 详细说明促成这种形式突触的生化机制 可塑性，并应提供洞察参与机制的长期- 哺乳动物中枢神经系统神经元功能的持久变化。这又反过来 要提高对发展机制的认识， 延长各种神经精神障碍的时间。

Long-term potentiation of synaptic transmission in the hippocampus (LTP) is a well-characterized, tractable model system for the study of mammalian learning and memory. Not only does a wide variety of evidence support a role for LTP in memory acquisition, the discrete, compact structure of the hippocampus allows for convenient monitoring of electrophysiological responses, and relative ease of in vitro manipulation. The development of the hippocampal slice preparation as a means to study LTP has provided a system in which to study the molecular and biophysical basis for this effect. The studies described in this application focus on the molecular mechanisms underlying the maintenance of LTP in the CA1 region of rat hippocampus. Using a variety of biochemical and pharmacological methods and approaches, we will investigate the involvement of protein kinase C in the maintenance of LTP. Specifically, the studies will address the following questions: By what mechanism is protein kinase C persistently activated in the maintenance phase of NMDA receptor-dependent LTP? How is the persistent activation of PKC reversed by depotentiating stimulation? These studies will serve as the foundation for future studies exploring in greater detail the biochemical mechanisms contributing to this form of synaptic plasticity, and should provide insight into mechanisms involved in long- lasting changes in neuronal function in the mammalian CNS. This in turn should increase our understanding of mechanisms for the development and prolongation of a variety of neuropsychiatric disorders.