αCaMKII在记忆不同阶段的作用及机制

项目名称： αCaMKII在记忆不同阶段的作用及机制

项目编号： No.31471077

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 曹晓华

作者单位： 华东师范大学

项目金额： 90万元

中文摘要： Alpha 钙离子/钙调蛋白依赖性蛋白激酶Ⅱ（Alpha Ca2+/calmodulin - dependent protein kinase II，αCaMKII）在记忆和突触可塑性中发挥重要作用。记忆是一个包括获得、巩固、储存和提取不同阶段的动态过程。然而目前的基因敲除技术不能实时控制蛋白质的活性，传统药理学方法又缺乏分子和区域特异性，制约了αCaMKII 在记忆各阶段作用及机制的研究。本项目选用可逆和可诱导αCaMKII 蛋白敲除小鼠αCaMKIIF89G/F89G，能够在体快速可逆、特异性地将前脑内源αCaMKII活性下调至不同水平，结合分子生物学、离体电生理学、在体多通道记录技术和整体行为学，从分子、细胞突触、神经网络和整体行为不同层次，系统地研究αCaMKII活性下调对记忆不同阶段的影响及机制，以揭示αCaMKII在记忆各阶段，以及在短时记忆不稳定性和记忆抹除中的作用机制。

中文关键词： Alpha钙调蛋白激酶II；学习记忆；突触可塑性；神经机制；海马

英文摘要： Alpha Ca2+/calmodulin-dependent protein kinase II(αCaMKII) plays an important role in synaptic plasticity and memory. Memory is considered to be a process that has several stages, including acquisition, consolidation,storage and retrieval. Due to the shortcomings of current genetic techniques (e.g., lack of precise temporal control of protein activity) and pharmacological methods (e.g., lack of the true molecular and regional specificity), the mechanism underlying the involvement of αCaMKII in the distinct stages of memory has not been well investigated. Here, We will take advantage of inducible and reversible protein knockout mice (αCaMKIIF89G/F89G),in which αCaMKII activity levels in forebrain can be manipulated on the scale of minutes inducibly and reversibly during each specific stage of memory processes. we will assess how various αCaMKII activity levels influence memory acquisition, consolidation,storage and retrieval by using molecular biological, in vitro electrophysiological, multi-channel recording and behavioral techniques. Our aim is to reveal the mechanisms underlying the involvement of αCaMKII in the distinct stages of memory, lability of short-term memory and memory erasure.

英文关键词： αCaMKII;Learning and memory;Synaptic plasticity;Neuromechanism;Hippocampus