β-arrestin在记忆再巩固中的作用及机制研究

研究发现部分G蛋白偶联受体参与记忆再巩固的形成，但具体的分子机制还不清楚。β-arrestin参与调控G蛋白偶联受体内吞和信号转导，然而β-arrestin biased信号通路的激活在中枢神经系统的作用不清楚。申请人前期研究工作首次发现β-arrestin通过调控杏仁核PKA的活性参与恐惧条件记忆的巩固。基于本项目申请人一直以来在学习记忆领域的研究兴趣和前期研究结果，旨在探求β-arrestin参与记忆再巩固的调控作用及调控的分子机制。本研究将采用β-arrestin全身敲除小鼠和条件性敲除小鼠，并结合慢病毒shRNA和腺相关病毒系统对β-arrestin表达进行干预，观察β-arrestin对物体辨别记忆和空间记忆的再巩固的影响，并试图阐述β-arrestin biased分子信号通路的激活如何调控记忆再巩固，从而发现β-arrestin在脑内的新功能。

Up to now the molecular mechanisms that regulate memory reconsolidation are still largely unknown. As the critical downstream negative regulator of G protein coupled receptor (GPCR), β-arrestin attenuates GPCR-mediated signal transduction and induce receptor internalization in an agonist-dependent manner. Due to the great distribution in the brain, the functions of β-arrestin in central nerves system attract more attention now. We have been focusing on the research of the neurological roles of β-arrestin for several years. We found that the negative regulation of PKA in amygdale by β-arrestin 2 / phosphodiesterase-4 complex was critical for fear conditioning. Based on our previous research interests and results, we try to demonstrate the role of β-arrestin in the reconsolidation of object recognition memory and spatial memory, then try to find out the new function of β-arrestin in the central nerves system. In this research, the β-arrestin global knockout mice and conditional knockout mice are used to perform the object recognition memory tasks. The lentivirus and associated adenovirus system to knockdown or expression β-arrestin are also introduced in this study to test the role of β-arrestin in memory reconsolidation. Then the neural plasticity and molecular mechanism regulated by β-arrestin in memory reconsolidation will be focused. This research will supply some neurobiological clues for the memory dynamic storage dependent neurocircuits and molecular mechanism.