非典型PKC在海马相关突触可塑性和学习记忆中的作用及其机制研究

项目名称： 非典型PKC在海马相关突触可塑性和学习记忆中的作用及其机制研究

项目编号： No.31471032

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： 陆巍

作者单位： 东南大学

项目金额： 87万元

中文摘要： 非典型PKC是PKC这个多基因蛋白激酶家族的一个亚类。在与学习记忆密切相关的脑区海马，非典型PKC包括PKCι/λ和PKMζ两个亚型。PKMζ在突触可塑性及记忆后期维持阶段发挥关键作用，但近两年PKMζ的这种作用受到强烈质疑，提示PKCι/λ可能是真正发挥作用的分子。因此，迫切需要澄清这两种非典型PKC的确切作用，这也是目前认知科学领域密切关注的一个热点问题。本实验室在LTP这个突触可塑性及学习记忆的细胞模型上，发现PKCι/λ通过磷酸化AMPA受体促进其上膜而发挥关键作用，提示其在学习记忆中的可能作用。本项申请拟在此基础上，综合使用脑片电生理、海马相关学习记忆行为测试及生化等实验方法，通过在体海马转染病毒以急性敲减PKCι/λ或PKMζ，以及采用条件性敲除小鼠，试图明确PKCι/λ或PKMζ在突触可塑性及学习记忆中的作用，并阐明其作用机制，为将来以非典型PKC为靶标的记忆干预提供新思路。

中文关键词： 突触可塑性；学习和记忆

英文摘要： The atypical PKCs (aPKCs) is one of the subgroups of PKC multigene family. In hippocampus, the brain region that is highly associated with learning and memory, only PKCι/λ and PKMζ of the aPKC are expressed. Numerous studies have found that PKMζ plays a critical role in the maintenance of late long-term plasticity (LTP) and long-term memory, thus is considered as a unique and important memory molecule. However, very recently the role of PKMζ has been strongly questioned, and the role of PKCι/λ is suggested. Thus, it is tempting to clarify the exact roles of these two isoforms of aPKCs, which is also a hot question receiving extensive attention and badly need to be addressed. Our recent study has found that PKCι/λ is the critical signaling molecule responsible for GluA1-containing AMPAR phosphorylation and synaptic incorporation at activated synapses during LTP expression. These findings suggest the potential role of PKCι/λ in learning and memory. Based on these findings, our present proposal aim to elucidate the role of atypical PKCs in hippocampal synaptic plasticity, learning and memory as well as their underlying mechanisms, employing a bunch of methods or animals including electrophysiological recording in acute brain slices, behavioral test of hippocampal-associated learning and memory, in vivo transfection of recombinant adeno-associated virus (rAAV2/8) containing PKCι/λ- or PKMζ-shRNA to specially knockdown either PKCι/λ or PKMζ, PKCι/λ or PKMζ knockdown animals. The present study will provide new insights to intervene memory process by targeting aPKCs.

英文关键词： synaptic plasticity;learning and memory