Crestani Ana Paula, Zacouteguy Boos Flávia, Haubrich Josué, Ordoñez Sierra Rodrigo, Santana Fabiana, Molina Johanna Marcela Duran, Cassini Lindsey de Freitas, Alvares Lucas de Oliveira, Quillfeldt Jorge Alberto
Psychobiology and Neurocomputation Lab, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Neurosciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Sci Rep. 2015 Sep 2;5:13633. doi: 10.1038/srep13633.
Memories can be destabilized by the reexposure to the training context, and may reconsolidate into a modified engram. Reconsolidation relies on some particular molecular mechanisms involving LVGCCs and GluN2B-containing NMDARs. In this study we investigate the interference caused by the presence of a distractor - a brief, unanticipated stimulus that impair a fear memory expression - during the reactivation session, and tested the hypothesis that this disruptive effect relies on a reconsolidation process. Rats previously trained in the contextual fear conditioning (CFC) were reactivated in the presence or absence of a distractor stimulus. In the test, groups reactivated in the original context with distractor displayed a reduction of the freezing response lasting up to 20 days. To check for the involvement of destabilization / reconsolidation mechanisms, we studied the effect of systemic nimodipine (a L-VGCC blocker) or intra-CA1 ifenprodil (a selective GluN2B/NMDAR antagonist) infused right before the reactivation session. Both treatments were able to prevent the disruptive effect of distraction. Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon. Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way.
再次暴露于训练环境中会使记忆变得不稳定，并可能重新巩固为经过修改的记忆痕迹。重新巩固依赖于一些特定的分子机制，涉及L型电压门控钙通道（LVGCCs）和含GluN2B的N-甲基-D-天冬氨酸受体（NMDARs）。在本研究中，我们调查了在重新激活阶段存在干扰物（一种短暂的、意外的刺激，会损害恐惧记忆的表达）所造成的干扰，并检验了这一破坏作用依赖于重新巩固过程的假设。先前接受情境恐惧条件反射（CFC）训练的大鼠在有或无干扰刺激的情况下被重新激活。在测试中，在有干扰物的原始环境中重新激活的组表现出持续长达20天的僵住反应减少。为了检查不稳定/重新巩固机制是否参与其中，我们研究了在重新激活阶段之前全身注射尼莫地平（一种L型电压门控钙通道阻滞剂）或在CA1区注射ifenprodil（一种选择性GluN2B/N-甲基-D-天冬氨酸受体拮抗剂）的效果。两种处理都能够防止干扰的破坏作用。ifenprodil的结果也支持了海马体是这种现象所在的假定脑结构的观点。我们的结果为一种行为学的、非侵入性的程序提供了一些证据，该程序能够长期破坏厌恶记忆。
