Soeter Marieke, Kindt Merel
Department of Clinical Psychology, University of Amsterdam Amsterdam, Netherlands ; Amsterdam Brain and Cognition, University of Amsterdam Amsterdam, Netherlands.
Front Behav Neurosci. 2015 May 18;9:122. doi: 10.3389/fnbeh.2015.00122. eCollection 2015.
Disrupting the process of memory reconsolidation may point to a novel therapeutic strategy for the permanent reduction of fear in patients suffering from anxiety disorders. However both in animal and human studies the retrieval cue typically involves a re-exposure to the original fear-conditioned stimulus (CS). A relevant question is whether abstract cues not directly associated with the threat event also trigger reconsolidation, given that anxiety disorders often result from vicarious or unobtrusive learning for which no explicit memory exists. Insofar as the fear memory involves a flexible representation of the original learning experience, we hypothesized that the process of memory reconsolidation may also be triggered by abstract cues. We addressed this hypothesis by using a differential human fear-conditioning procedure in two distinct fear-learning groups. We predicted that if fear learning involves discrimination on basis of perceptual cues within one semantic category (i.e., the perceptual-learning group, n = 15), the subsequent ambiguity of the abstract retrieval cue would not trigger memory reconsolidation. In contrast, if fear learning involves discriminating between two semantic categories (i.e., categorical-learning group, n = 15), an abstract retrieval cue would unequivocally reactivate the fear memory and might subsequently trigger memory reconsolidation. Here we show that memory reconsolidation may indeed be triggered by another cue than the one that was present during the original learning occasion, but this effect depends on the learning history. Evidence for fear memory reconsolidation was inferred from the fear-erasing effect of one pill of propranolol (40 mg) systemically administered upon exposure to the abstract retrieval cue. Our finding that reconsolidation of a specific fear association does not require exposure to the original retrieval cue supports the feasibility of reconsolidation-based interventions for emotional disorders.
破坏记忆再巩固过程可能为永久性减轻焦虑症患者的恐惧指明一种新的治疗策略。然而，在动物和人体研究中，检索线索通常都涉及再次暴露于最初的恐惧条件刺激（CS）。一个相关的问题是，鉴于焦虑症往往源于替代性或不显眼的学习，而对于这些学习不存在明确的记忆，那么与威胁事件没有直接关联的抽象线索是否也会触发再巩固。就恐惧记忆涉及对原始学习经历的灵活表征而言，我们假设记忆再巩固过程也可能由抽象线索触发。我们通过在两个不同的恐惧学习组中使用差异性人类恐惧条件作用程序来验证这一假设。我们预测，如果恐惧学习涉及基于一个语义类别内的感知线索进行辨别（即感知学习组，n = 15），那么随后抽象检索线索的模糊性将不会触发记忆再巩固。相反，如果恐惧学习涉及在两个语义类别之间进行辨别（即类别学习组，n = 15），一个抽象检索线索将明确地重新激活恐惧记忆，并且随后可能触发记忆再巩固。在这里我们表明，记忆再巩固确实可能由不同于原始学习时出现的线索触发，但这种效应取决于学习历史。通过在暴露于抽象检索线索时全身给予一片普萘洛尔（40毫克）的恐惧消除效应推断出恐惧记忆再巩固的证据。我们的发现，即特定恐惧关联的再巩固不需要暴露于原始检索线索，支持了基于再巩固的情绪障碍干预措施的可行性。
