Abstract
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.
Highlights
To survive and reproduce, animals need to learn about the motivational significance of environmental cues; predicting the presence of a predator or a potential mate based on learned or conditioned stimuli (CSs) in the environment allows animals to prepare a behavioural response rather than reacting to an unpredicted threat or reward, actingMemory Persistence and Inhibition as an unconditioned stimulus (US)
Studies in both vertebrates and invertebrates have shown that destabilisation of the original CS-US memory at retrieval relies upon a specific amount of prediction error—enough for the original memory to be sufficiently inaccurate to require updating, but not so much that the experience is consolidated as a new memory
When the conditions during extinction training are more similar to the original training context, it is more likely that the original memory will be updated or ‘‘unlearned.’’ According to Gershman et al (2017), updating mechanisms depend on the reconsolidation of the original memory, while new learning is dependent upon the extinction processes
Summary
Animals need to learn about the motivational significance of environmental cues; predicting the presence of a predator or a potential mate based on learned or conditioned stimuli (CSs) in the environment allows animals to prepare a behavioural response rather than reacting to an unpredicted threat or reward, acting. Reducing the impact of maladaptive memories on behavior could be achieved by targeting one of two memory retrievaldependent processes that engage different mnemonic processes: disrupting memory reconsolidation or enhancing extinction Both of these processes depend upon re-exposure to the pavlovian CSs or ‘‘trigger stimuli,’’ and on inducing a ‘‘mismatch’’ between what is expected and what occurs (more formally referred to as ‘‘prediction error’’). It is hypothesised that behavioural inhibition results from the formation of a new ‘‘CS-noUS’’ associative memory that prevents expression of the original CS-US memory without erasing it (Bouton, 2004) Both reconsolidation disruption and extinction enhancement are potentially valuable treatment strategies able to reduce the impact of cue-dependent maladaptive memories on behavior (Figure 2). A better understanding of some of the subtleties in boundary conditions—along with a non-behavioural, independent marker of memory destabilisation—would likely provide great insight into the apparent fragility of reconsolidation interference effects
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