Memory reconsolidation may be disrupted by a distractor stimulus presented during reactivation

Abstract

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.

Calcium/calmodulin‐dependent kinase II and memory destabilization: a new role in memory maintenance

“…A GluN2B-induced memory destabilization was also later described by Crestani et al (2015) and Ferrer Monti et al (2016). Both used a distractor stimulus to erase memory in a memory retrieval-dependent matter.…”

“…Aside from the involvement of Ca 2+ influx, which is mediated by L‐type voltage‐gated calcium channels (Crestani et al . ), not much is known about the mechanism.…”

“…A GluN2B‐induced memory destabilization was also later described by Crestani et al . () and Ferrer Monti et al . ().…”

“…Both used a distractor stimulus to erase memory in a memory retrieval-dependent matter. Crestani et al (2015) used an air puff during retrieval as a distractor to induce contextual fear memory impairment. This impairment could be blocked by intra-CA1 injection of the GluN2B antagonist ifenprodil, prior to retrieval session.…”

Interference Conditions of the Reconsolidation Process in Humans: The Role of Valence and Different Memory Systems

“…Animal studies showed that the reconsolidation of a fearful memory could be disrupted after its reactivation followed by a distractor stimuli (air puff) or the exploration of a hole board (Boccia et al, 2005; Crestani et al, 2015). In humans, for example, Schwabe and Wolf (2009) showed that learning a neutral story after reactivation of different autobiographical memories (positive, negative, or neutral), reduced specifically the retention of neutral memories.…”