记忆提取及再巩固是记忆动态存储的重要阶段。记忆提取后，已经巩固的记忆被再次激活，原先稳定的记忆变得脆弱易变，在再巩固后重新形成稳定的记忆。在此时间窗内进行干预，记忆能被擦除、强化、修改或更新。因此理解记忆提取-再巩固的机制具有重要的科学意义，对于治疗相关疾病也具有重要的价值。我们在前期工作中发现，记忆的再巩固并不依赖于G蛋白信号通路，而是由β-arrestin偏向性蛋白合成信号通路所介导；联合型记忆的提取和再巩固可能依赖于特定脑区的少量神经元（痕迹细胞）。本项目将在此基础上，采用条件性恐惧和位置偏爱记忆模型，运用即早基因启动子驱动的转基因鼠以及Cre/loxp病毒表达体系，结合转录组和翻译组分析，探讨联合型记忆提取-再巩固依赖的信号转导网络，揭示记忆提取-再巩固的痕迹细胞的作用和分子标记物，解析记忆痕迹细胞的神经环路组成和功能重塑，阐述记忆再巩固的分子和环路机制。

Memory reconsolidation, a rebuilding process triggered by recall of an established memory, depends on de novo protein synthesis and β-adrenergic signaling, but the underlying mechanisms have not been identified. Our previous study demonstrates that β-arrestin-biased β-adrenergic signaling regulates reconsolidation of object recognition memory and reveals the potential for β-arrestin-biased ligands in the treatment of memory-related disorders. Our preliminary study also indicates that a small population of neurons correspond to associative memory storage, suggesting a cellular correlate of a memory engram. However, many questions, including what proteins are synthesized during memory reconsolidation process, whether the de novo protein synthesis occurs in the engram cell, and whether β-arrestin-biased signaling in these cells mediates memory reconsolidation and synaptic remodeling through regulation of protein synthesis, are to be addressed. In this project, we plane to use conditioned fear memory and conditioned place preference memory as models of associative memory and focus our study on basic scientific questions about the molecular and circuitry mechanisms of associative memory reconsolidation, and reveal the key role of β-arrestin-biased β-adrenergic translational signaling pathway in regulation of gene expression in reconsolidation-related engram cells and the reconsolidation of associative memory.