中国科学院昆明动物研究所周启心等研究人员合作发现，与情境性恐惧记忆提取相关的时间依赖性转录动力学，揭示二肽基肽酶9在记忆再巩固中的功能。2024年12月2日，《神经科学通报》杂志在线发表了这项成果。

研究人员对近期记忆阶段不同时间点的记忆提取进行了转录组分析。差异表达分析和短时间序列表达挖掘器（STEM）描绘的基因表达时间模式表明，大多数差异基因表达发生在48小时，并且在48小时转录上调最显著的STEM簇表现出最大的差异。

随后，研究人员筛选了与此相关的差异表达基因，除了二肽基肽酶9（DPP9）以外，这些基因符合该簇已知涉及学习和记忆过程的基因表达模式。进一步的定量聚合酶链式反应验证和药理干预表明，DPP9参与48小时的恐惧记忆提取，并且病毒载体介导的DPP9过表达抵消了48小时提取引起的恐惧记忆衰减。

综上所述，这些研究结果表明，近期记忆提取诱导了时间依赖性的基因表达模式，并提供了DPP9在恐惧记忆提取诱导的再巩固中作用的新证据。

研究人员表示，关于记忆的形成和巩固的众多研究表明，记忆过程具有阶段性依赖和动态调控的特征。记忆提取作为记忆内容的唯一表现形式，并且是一种诱导记忆再巩固的主动记忆处理方式，近年来受到越来越多的关注。尽管记忆提取诱导的再巩固的分子机制已逐渐被揭示，但对于这一过程的时间依赖性调控机制的理解仍然不足。

附：英文原文

Title: Time-Dependent Transcriptional Dynamics of Contextual Fear Memory Retrieval Reveals the Function of Dipeptidyl Peptidase 9 in Reconsolidation

Author: Guo, Wen-Ting, Li, Wen-Xing, Liu, Yu-Chen, Zhao, Ya-Bo, Xu, Lin, Zhou, Qi-Xin

Issue&Volume: 2024-12-02

Abstract: Numerous studies on the formation and consolidation of memory have shown that memory processes are characterized by phase-dependent and dynamic regulation. Memory retrieval, as the only representation of memory content and an active form of memory processing that induces memory reconsolidation, has attracted increasing attention in recent years. Although the molecular mechanisms specific to memory retrieval-induced reconsolidation have been gradually revealed, an understanding of the time-dependent regulatory mechanisms of this process is still lacking. In this study, we applied a transcriptome analysis of memory retrieval at different time points in the recent memory stage. Differential expression analysis and Short Time-series Expression Miner (STEM) depicting temporal gene expression patterns indicated that most differential gene expression occurred at 48 h, and the STEM cluster showing the greatest transcriptional upregulation at 48 h demonstrated the most significant difference. We then screened the differentially-expressed genes associated with that met the expression patterns of those cluster-identified genes that have been reported to be involved in learning and memory processes in addition to dipeptidyl peptidase 9 (DPP9). Further quantitative polymerase chain reaction verification and pharmacological intervention suggested that DPP9 is involved in 48-h fear memory retrieval and viral vector-mediated overexpression of DPP9 countered the 48-h retrieval-induced attenuation of fear memory. Taken together, our findings suggest that temporal gene expression patterns are induced by recent memory retrieval and provide hitherto undocumented evidence of the role of DPP9 in the retrieval-induced reconsolidation of fear memory.

DOI: 10.1007/s12264-024-01324-w

Source: https://link.springer.com/article/10.1007/s12264-024-01324-w