On the Destabilization of Maladaptive Memory: Updates and Future Perspectives

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Background

Memories define who we are, without them we would be unable to behaviorally express what we learn. However, throughout life, we confront events that can cause the formation of persistent distressing memories. These maladaptive representations are a hallmark of several psychiatric conditions, such as posttraumatic stress disorder, anxiety, addictions, and mood disorders. Patients suffering from these disorders share a common feature: their pathological memories are resistant to modification and prone to relapse after psychotherapeutic interventions. Therefore, with the purpose of developing new strategies to attenuate the recurrent, undesirable thoughts and feelings afflicting these patients, much effort from basic and clinical research has been dedicated to understanding the neural mechanism underlying the expression of dysfunctional memories.

Newly acquired information is initially labile, requiring a time-dependent stabilization process called consolidation to be stored as long-term memory. Traditionally, it has been thought that consolidated memories are immutable. However, research in the last two decades shows that, under appropriate conditions, long-term memories can become unstable again when reactivated and to persist must undergo a restabilization process called reconsolidation. During this destabilization/re-stabilization cycle, long-term memories can be changed, updated with new information or erased. That is why reconsolidation has gained much attention in the last few years, given that behavioral and pharmacological manipulation of dysfunctional memories following retrieval could help attenuate their expression. However, memories are not always destabilized when recalled, which limits the therapeutic value of reconsolidation-based strategies.

Memory destabilization cannot be behaviorally expressed and its induction can only be evaluated in combination with pharmacological treatments that interrupt memory restabilization after recall. Because of this, most research on memory reconsolidation has focused on understanding the molecular mechanisms responsible for restabilizing reactivated memories. Therefore, characterizing the molecular and behavioral triggers of reactivation-induced memory destabilization may open new opportunities to modulate maladaptive memories and help us to understand why some mnemonic representations, such as those related to compulsions, traumas and phobias are resistant to modification and less responsive to pharmacological treatments.

The main aim of this Research Topic is to highlight latest findings of basic, translational, and clinical research studies on maladaptive memories destabilization. We would like to include in this issue, manuscripts addressing the memory reactivation boundary conditions that trigger memory destabilization as well as the current state of knowledge on neurotransmitter systems and signal transduction pathways regulating this process. Original Research articles, Mini Reviews, opinions and perspectives in humans or animal models are welcome.

The scope of this Research Topic encompasses, but is not limited to, the following themes:

• Conditions that constrain/facilitate retrieval-induced memory destabilization;
• Molecular mechanisms of memory destabilization: signaling pathways and neural circuits;
• Neurophysiological signatures of memory destabilization;
• Non-invasive interventions aimed to induce maladaptive memory destabilization;
• Memory destabilization in reactivation–extinction procedures.

Keywords: fear memory, addiction, reconsolidation, reactivation, extinction

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