CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
Neuropsychopharmacology. 2023 Jan;48(2):327-340. doi: 10.1038/s41386-022-01477-0. Epub 2022 Oct 27.
Extinction training during the reconsolidation window following memory recall is an effective behavioral pattern for promoting the extinction of pathological memory. However, promoted extinction by recall-extinction procedure has not been universally replicated in different studies. One potential reason for this may relate to whether initially acquired memory is successfully activated. Thus, the methods for inducing the memory into an active or plastic condition may contribute to promoting its extinction. The aim of this study is to find and demonstrate a manipulatable neural circuit that engages in the memory recall process and where its activation improves the extinction process through recall-extinction procedure. Here, naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice was mainly used as a pathological memory model. We found that the locus coeruleus (LC)-dentate gyrus (DG) circuit was necessary for CPA memory recall and that artificial activation of LC inputs to the DG just prior to initiating a recall-extinction procedure significantly promoted extinction learning. We also found that activating this circuit caused an increase in the ensemble size of DG engram cells activated during the extinction, which was confirmed by a cFos targeted strategy to label cells combined with immunohistochemical and in vivo calcium imaging techniques. Collectively, our data uncover that the recall experience is important for updating the memory during the reconsolidation window; they also suggest a promising neural circuit or target based on the recall-extinction procedure for weakening pathological aversion memory, such as opioid withdrawal memory and fear memory.
在记忆回忆后的再巩固窗口期间进行灭绝训练是促进病理性记忆灭绝的有效行为模式。然而，在不同的研究中，回忆-灭绝程序促进的灭绝并没有被普遍复制。造成这种情况的一个潜在原因可能与最初获得的记忆是否被成功激活有关。因此，将记忆诱导到活跃或可塑状态的方法可能有助于促进其灭绝。本研究的目的是寻找和证明一个可操纵的神经回路，该回路参与记忆回忆过程，并且其激活通过回忆-灭绝程序改善了灭绝过程。在这里，纳洛酮诱发的吗啡依赖小鼠条件性位置厌恶（CPA）主要用作病理性记忆模型。我们发现蓝斑（LC）-齿状回（DG）回路是 CPA 记忆回忆所必需的，并且在开始回忆-灭绝程序之前，人工激活 LC 对 DG 的输入显著促进了灭绝学习。我们还发现，激活该回路导致在灭绝过程中激活的 DG 印记细胞的集合大小增加，这通过结合 cFos 靶向策略标记细胞的免疫组织化学和体内钙成像技术得到证实。总之，我们的数据揭示了回忆体验对于在再巩固窗口期间更新记忆很重要；它们还基于回忆-灭绝程序，为削弱病理性厌恶记忆（如阿片类药物戒断记忆和恐惧记忆）提供了一个有前途的神经回路或靶点。
