Modulation of memory reconsolidation by adjacent novel tasks: timing defines the nature of change.

Reconsolidation turns memories into a responsive state that allows their modulation until they stabilize again. This phenomenon attracted remarkable attention due to its potential impact on therapeutics and education. Recent evidence revealed that different memories undergo reconsolidation via a behavioral tagging process. Thus, their re-stabilization involves setting "reconsolidation-tags" and synthesizing plasticity-related proteins for their capture at the tagged sites. Here, we studied the possibility of affecting these fundamental mechanisms to modulate reconsolidation. Our findings, in laboratory rats, indicate that exploring a novel environment 60 min before or after memory reactivation improves spatial object recognition memory by promoting protein synthesis. Conversely, experiencing novelty immediately after reactivation impairs the reconsolidation by affecting the tags. Similar effects, but with a different optimal time window for improvement, occur in inhibitory avoidance memory. These results highlight the possibility of modulating existing memories using non-invasive interventions that selectively affect the fundamental mechanisms of behavioral tagging during their reconsolidation.

Behavioral tagging underlies memory reconsolidation.

Memory reconsolidation occurs when a retrieving event destabilizes transiently a consolidated memory, triggering thereby a new process of restabilization that ensures memory persistence. Although this phenomenon has received wide attention, the effect of new information cooccurring with the reconsolidation process has been less explored. Here we demonstrate that a memory-retrieving event sets a neural tag, which enables the reconsolidation of memory after binding proteins provided by the original or a different contiguous experience. We characterized the specific temporal window during which this association is effective and identified the protein kinase A (PKA) and the extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathways as the mechanisms related to the setting of the reconsolidation tag and the synthesis of proteins. Our results show, therefore, that memory reconsolidation is mediated by a "behavioral tagging" process, which is common to different memory forms. They represent a significant advance in understanding the fate of memories reconsolidated while being adjacent to other events, and provide a tool for designing noninvasive strategies to attenuate (pathological/traumatic) or improve (education-related) memories.