Guo Wen-Ting, Li Wen-Xing, Liu Yu-Chen, Zhao Ya-Bo, Xu Lin, Zhou Qi-Xin
Key Laboratory of Animal Models and Human Disease Mechanisms, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650204, China.
Neurosci Bull. 2025 Jan;41(1):16-32. doi: 10.1007/s12264-024-01324-w. Epub 2024 Dec 2.
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.
众多关于记忆形成和巩固的研究表明，记忆过程具有阶段依赖性和动态调节的特点。记忆提取作为记忆内容的唯一表征以及诱导记忆重新巩固的记忆处理的一种活跃形式，近年来受到了越来越多的关注。尽管记忆提取诱导的重新巩固所特有的分子机制已逐渐被揭示，但对这一过程的时间依赖性调节机制仍缺乏了解。在本研究中，我们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。差异表达分析和描绘时间基因表达模式的短时序列表达挖掘器（STEM）表明，大多数差异基因表达发生在48小时，并且在48小时显示出最大转录上调的STEM簇表现出最显著的差异。然后，我们筛选出与除二肽基肽酶9（DPP9）之外已报道参与学习和记忆过程的那些簇识别基因的表达模式相符的差异表达基因。进一步的定量聚合酶链反应验证和药理学干预表明，DPP9参与48小时恐惧记忆提取，并且病毒载体介导的DPP9过表达抵消了48小时提取诱导的恐惧记忆减弱。综上所述，我们的研究结果表明，近期记忆提取可诱导时间基因表达模式，并提供了迄今未记录的证据证明DPP 在提取诱导的恐惧记忆重新巩固中的作用。
