Retrieval-dependent mechanisms affecting emotional memory persistence: reconsolidation, extinction, and the space in between

Maladaptive emotional memories contribute to the persistence of many mental health disorders, and therefore the prospect of disrupting these memories to produce long-term reductions in relapse is of great clinical appeal. Reducing the impact of maladaptive emotional memories on behaviour could be achieved by two retrieval-dependent manipulations that engage separate mnemonic processes: “reconsolidation disruption” and “extinction enhancement.” Extinction occurs during a prolonged re-exposure session in the absence of the expected emotional outcome and is widely accepted as reflecting the formation of a new, inhibitory memory that prevents behavioural expression of the original trace. Reconsolidation, by contrast, involves the destabilisation of the original memory, allowing for subsequent updating and restabilisation in specific brain regions, unless the re-stabilization process is prevented through specific pharmacological or behavioural interventions. Both destabilisation of the original memory and memory extinction require that re-exposure induces prediction error—a mismatch between what is expected and what actually occurs—but the parameters that allow reconsolidation and extinction to occur, and control the transition between them, have not been well-characterised. Here, we review what is known about the induction of memory destabilisation and extinction, and the transition period that separates these mnemonic processes, drawing on preclinical and clinical examples. A deeper understanding of the processes that determine the alternative routes to memory persistence or inhibition is critical for designing new and more reliable clinical treatments targeting maladaptive emotional memories.