Haubrich Josue, Crestani Ana P, Cassini Lindsey F, Santana Fabiana, Sierra Rodrigo O, Alvares Lucas de O, Quillfeldt Jorge A
1] Psychobiology and Neurocomputation Lab, Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil [2] Neurosciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Neuropsychopharmacology. 2015 Jan;40(2):315-26. doi: 10.1038/npp.2014.174. Epub 2014 Jul 15.
The capacity to adapt to new situations is one of the most important features of memory. When retrieved, memories may undergo a labile state that is sensitive to modification. This process, called reconsolidation, can lead to memory updating through the integration of new information into a previously consolidated memory background. Thus reconsolidation provides the opportunity to modify an undesired fear memory by updating its emotional valence to a less aversive level. Here we evaluated whether a fear memory can be reinterpreted by the concomitant presentation of an appetitive stimulus during its reactivation, hindering fear expression. We found that memory reactivation in the presence of appetitive stimuli resulted in the suppression of a fear response. In addition, fear expression was not amenable to reinstatement, spontaneous recovery, or rapid reacquisition. Such effect was prevented by either systemic injection of nimodipine or intra-hippocampal infusion of ifenprodil, indicating that memory updating was mediated by a reconsolidation mechanism relying on hippocampal neuronal plasticity. Taken together, this study shows that reconsolidation allows for a 're-signification' of unwanted fear memories through the incorporation of appetitive information. It brings a new promising cognitive approach to treat fear-related disorders.
适应新情况的能力是记忆最重要的特征之一。当记忆被提取时，可能会经历一个对修改敏感的不稳定状态。这个过程称为重新巩固，它可以通过将新信息整合到先前巩固的记忆背景中，从而实现记忆更新。因此，重新巩固提供了一个机会，通过将不想要的恐惧记忆的情感效价更新到不那么厌恶的水平来修改它。在这里，我们评估了在恐惧记忆重新激活期间伴随呈现一个愉悦刺激，是否可以重新解释该恐惧记忆，从而抑制恐惧表达。我们发现，在有愉悦刺激的情况下进行记忆重新激活会导致恐惧反应受到抑制。此外，恐惧表达对恢复、自发恢复或快速重新习得均不敏感。全身注射尼莫地平或海马内注射ifenprodil均可阻止这种效应，这表明记忆更新是由一种依赖海马神经元可塑性的重新巩固机制介导的。综上所述，本研究表明重新巩固通过纳入愉悦信息，实现了对不想要的恐惧记忆的“重新赋义”。它为治疗恐惧相关障碍带来了一种新的、有前景的认知方法。
