Parts of the projects are now at an advanced stage despite the severe setbacks caused by the COVID-19 pandemic and related experimental challenges. The work has led to three manuscripts, one of which is accepted in principle and another currently under revision. Our findings indicate that the neural circuits recruited during learning determine how memory becomes sensitive to destabilization. This suggests that the conditions present during learning set the stage for whether and how memory reconsolidation can be triggered, ultimately influencing memory stability. Importantly, these principles appear to be general and apply across different types of memory. Furthermore, we find that memory reconsolidation is not restricted to accessible memories but can impact the recovery of forgotten memories and change their content.
Although speculative at this stage, if these mechanisms prove to be conserved across species, they could have important translational implications. In human patients, detailed assessment of the learning conditions under which maladaptive memories were formed may improve treatment strategies. For instance, clinical studies have shown that drugs such as propranolol can interfere with memory reconsolidation; however, if destabilization is not triggered, such treatments may be ineffective. Understanding the factors that enable or prevent destabilization could therefore enhance therapeutic outcomes, inform expectation management, and guide the use of alternative interventions. Moreover, if retrieval protocols can address subjectively forgotten memories, strategies to target remote maladaptive memories may need to be reconsidered.
More broadly, the ability to bias memories toward being rewritten has implications beyond clinical contexts. Adjusting learned behaviors and modifying stored information are essential for adaptive decision-making in everyday life. Thus, elucidating how memories can be selectively destabilized and updated may ultimately benefit individuals suffering from traumatic experiences as well as those seeking to overcome maladaptive behavioral routines.