ERK Regulation of Hippocampal Potassium Channels

海马钾通道的 ERK 调节

• 批准号: 6936799
• 负责人: SHARI G BIRNBAUM
• 金额: $ 3.97万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-18 至 2006-02-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936799
• 关键词: action potentials; antibody; biological signal transduction; dendrites; enzyme activity; genetically modified animals; hippocampus; immunologic substance development /preparation; laboratory mouse; laboratory rat; learning; long term memory; long term potentiation; membrane activity; mitogen activated protein kinase; neural plasticity; phosphorylation; postdoctoral investigator; potassium channel; protein protein interaction; synapses

DESCRIPTION (provided by applicant): ERK/MAPK activation is a critical component of the signaling mechanisms that regulate synaptic plasticity and the formation of long-term memories in a large variety of species. The substrates for ERK phosphorylation that contribute to the induction of LTP and long-term memory formation are largely unknown. One intriguing possibility is the potassium channel, Kv4.2, which forms a transient A-type potassium current (IA) in pyramidal neurons of the hippocampus and regulates membrane excitability. ERK activation decreases IA and enhances the amplitude of back-propagating action potentials in pyramidal cell dendrites. These changes may play an important role in mediating learning-related neuronal plasticity in the brain. This proposal will investigate the role of ERK phosphorylation of Kv4.2 in the hippocampus in the formation of memories and modulation of synaptic plasticity. Antibodies to phosphorylated Kv4.2 will be developed and used to assess any changes in ERK-mediated Kv4.2 phosphorylation following induction of LTP as well as a hippocampus-dependent learning task, contextual fear-conditioning. The role of Kv4.2 in synaptic plasticity and learning and memory will be further evaluated using Kv4.2 knockout mice. This research will enhance our understanding of the molecular changes that support learning and synaptic plasticity, as well as provide insights into disease states such as mental retardation.

描述（由申请人提供）：ERK/MAPK激活是调节突触可塑性和多种物种长期记忆形成的信号传导机制的关键组成部分。ERK磷酸化的底物，有助于诱导LTP和长期记忆的形成在很大程度上是未知的。一个有趣的可能性是钾通道Kv4.2，其在海马锥体神经元中形成瞬时A型钾电流（IA）并调节膜兴奋性。ERK激活降低IA并增强锥体细胞树突中反向传播动作电位的幅度。这些变化可能在介导大脑中与学习相关的神经元可塑性方面发挥重要作用。本研究将探讨海马Kv4.2的ERK磷酸化在记忆形成和突触可塑性调节中的作用。将开发磷酸化Kv4.2的抗体，并用于评估诱导LTP后ERK介导的Kv4.2磷酸化的任何变化以及依赖于校园的学习任务，情境恐惧条件反射。将使用Kv4.2敲除小鼠进一步评估Kv4.2在突触可塑性和学习记忆中的作用。这项研究将增强我们对支持学习和突触可塑性的分子变化的理解，并提供对精神发育迟滞等疾病状态的见解。