BIOCHEMICAL MECHANISMS FOR LONG-TERM POTENTIATION

长时程增强的生化机制

• 批准号: 2416201
• 负责人: John David Sweatt
• 金额: $ 16.84万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2416201
• 关键词: NMDA receptors; autoradiography; behavioral /social science research tag; biochemistry; electrophysiology; enzyme activity; enzyme induction /repression; enzyme mechanism; hippocampus; immunoprecipitation; isozymes; laboratory rat; learning; long term potentiation; memory; neurophysiology; phosphorylation; protein kinase C; protein structure function; statistics /biometry; western blottings

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.

海马突触传递的长期增强（LTP） 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 在内存采集、离散、紧凑等方面的作用 海马体的结构可以方便地监测 电生理反应和体外相对容易 操纵。海马切片制剂的开发 研究 LTP 的方法提供了一个研究分子的系统 以及这种效应的生物物理学基础。本文中描述的研究 应用重点关注维护的分子机制 大鼠海马 CA1 区 LTP 的变化。 使用各种 生化和药理学方法和途径，我们将 研究蛋白激酶 C 在维持 LTP。具体来说，这些研究将解决以下问题： 蛋白激酶C持续激活的机制是什么 NMDA 受体依赖性 LTP 的维持期？怎样的坚持 去势刺激可逆转 PKC 的激活？ 这些研究 将作为未来研究探索更大范围的基础 详细介绍了这种突触形式的生化机制 可塑性，并且应该提供对长期相关机制的深入了解 哺乳动物中枢神经系统神经元功能的持久变化。 这反过来 应增加我们对发展机制的理解 各种神经精神疾病的延长。