Identification of the Similarities and Differences of Molecular Networks Associated With Fear Memory Formation, Extinction, and Updating in the Amygdala.
Identification of the Similarities and Differences of Molecular Networks Associated With Fear Memory Formation, Extinction, and Updating in the Amygdala.
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杏仁核中与恐惧记忆形成、消退和更新相关的分子网络的相似性和差异性的识别
DOI：
10.3389/fnmol.2021.778170
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发表时间：
2021
影响因子：
4.8
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Su J;Li P;Zhuang Q;Chen X;Zhang X;Li X;Wang J;Yu X;Wang Y
恐惧记忆异常是导致创伤后应激障碍（PTSD）、焦虑症等精神障碍的重要致病因素之一。临床上，以恐惧记忆消退为原理的暴露疗法虽然对这些疾病有一定疗效，但在某些病例中仍会频繁复发。在恐惧记忆消退前的某个时间窗内进行记忆的提取，可以有效地解决这些问题。因此，一般认为，恐惧记忆的消退是形成新的安全记忆竞争性抑制原有恐惧记忆的结果，而提取-消退操作是对原有恐惧记忆的更新或擦除，因此具有更大的临床治疗潜力。然而，参与恐惧记忆更新的详细分子网络，特别是环状RNA（circRNA），以及与恐惧消退的差异，仍然是未知的。本研究采用全转录测序技术，系统观察了恐惧记忆形成、消退和更新后小鼠基底外侧杏仁核中mRNA、microRNA（miRNA）、长链非编码RNA（lncRNA）和circRNA的表达，并通过多种组间比较和生物信息学分析，寻找差异表达的RNA，丰富其功能，构建分子相互作用网络。此外，竞争内源性RNA（ceRNA）的分子网络和转录调控网络的候选circRNA的构建。通过这些分析，我们发现大约有10%的分子同时参与了恐惧记忆的消退和形成，但在恐惧记忆的消退和更新过程中，分子及其信号通路几乎完全不同。本研究揭示了一个较为详细的恐惧记忆更新的分子网络，为进一步的机制研究提供了新的方向，并有助于开发基于这些关键分子调控的恐惧记忆干预的具体物理方法。
Abnormality of fear memory is one of the important pathogenic factors leading to post-traumatic stress disorder (PTSD), anxiety disorder, and other mental disorders. Clinically, although exposure therapy, which is based on the principle of fear memory extinction, has a certain effect on these diseases, it still relapses frequently in some cases. These troubles can be effectively solved by retrieving the memory in a certain time window before the extinction of fear memory. Therefore, it is generally believed that the extinction of fear memory is the result of forming new safe memory to competitively inhibit the original fear memory, while the retrieval-extinction operation is the updating or erasure of the original fear memory, thus, which has greater clinical therapeutic potential. However, what are the detailed molecular networks, specifically the circular RNAs (circRNAs), involved in fear memory updating, and the differences with fear extinction, are still unknown. In this study, we systematically observed the expression of mRNAs, microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circRNAs in the basolateral amygdala of mice after fear memory formation, extinction, and updating by whole-transcriptional sequencing, then a variety of inter-group comparison and bioinformatics analysis were used to find the differential expressed RNAs, enrich the function of them, and construct the molecular interaction networks. Moreover, competing endogenous RNA (ceRNA) molecular networks and transcriptional regulatory networks for the candidate circRNAs were constructed. Through these analyses, we found that about 10% of molecules were both involved in the fear memory extinction and formation, but the molecules and their signaling pathways were almost completely different between fear memory extinction and updating. This study describes a relatively detailed molecular network for fear memory updating, which might provide some novel directions for further mechanism research, and help to develop a specific physical method for fear memory intervention, based on the regulation of these key molecules.
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