Memory Reconsolidation and Extinction Have Distinct Temporal and Biochemical Signatures

Mappe: Boundaties/2004 a

Akinobu Suzuki, 1 Sheena A. Josselyn, 3,4Paul W. Frankland,3,4 Shoichi Masushige,1,2 Alcino J. Silva, 4 and Satoshi Kid


Reonsolidation and extinction, two opposing processes triggered by memory retrieval, have distinct biochemical signatures: cannabinoid receptor 1 or L-type voltage-gated calcium channels blocks extinction but not reconsolidation. These studies demonstrate the dynamic nature of memory processing after retrieval and represent a first step toward a molecular dissection of underlying

Experimental extinction does not reflect forgetting of the original memory trace but rather reflects new learning.

Memory retrieval may initiate two potentially dissociable but opposite processes: reconsolidation and extinction. Re-consolidation acts to stabilize, whereas extinction tends to weaken, the expression of the original memory. The duration of a reminder event may be an important determinant of subsequent memory processing: brief reminders lead to reconsolidation, whereas longer reminders result in memory extinction (Debiec et al., 2002; Eisenberg et al., 2003; Pedreira and Maldonado, 2003).

There has been renewed interest in memory processing after retrieval: brief exposure to the CS seems to trigger a second wave of memory consolidation (reconsolidation), whereas prolonged exposure to the CS leads to the formation of a new memory that competes with the original memory (extinction)

We provided a systematic demonstration of how reexposure duration, the age of the memory, and the strength of the memory interact to influence behavior in tasks that model declarative memory.

The results presented here reveal three distinct timedependent phases of memory processing after memory retrieval. 

During the first phase, the retrieved memory is in a state that precedes both the reconsolidation and extinction processes. Further extending reexposure, however, initiates the protein synthesis-dependent reconsolidation processes required for the stability of the memory trace. Hence, blocking protein synthesis during this second phase compromises the long-term stability of the trace. Finally, prolonged reexposures to the CS in the absence of the US trigger the formation of a new memory trace that encodes the dissociation between the CS and the US (CS–no US; extinction memory), therefore competing with the original memory (CS–US). Inhibition of protein synthesis at this stage blocks the formation of this new extinction memory, leaving expression of the original memory unchanged. It is important to note that our results also indicate that there is an interaction between the extinction and reconsolidation processes: although blocking protein synthesis during short reexposures (reconsolidation) disrupts the original memory, blocking protein synthesis during prolonged reexposure, conditions in which both reconsolidation and extinction would be expected to be initiated, leaves the original memory unaffected.

Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Mappe: Authors/D.Schiller/ 2013 a

Daniela Schiller a,1 , Jonathan W. Kanen b , Joseph E. LeDoux c,d,1 , Marie-H. Monfils e , and Elizabeth A. Phelps

Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the non-reminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders.


Memory Reconsolidation Interference as an Emerging Treatment for Emotional Disorders: Strengths, Limitations, Challenges, and Opportunities


Mappe: Boundaries 2017 a + Merenl Kindt

Tom Beckers and Merel Kindt

Experimental research on emotional memory reconsolidation interference, or the induction of amnesia for previously established emotional memory, has a long tradition, but the potential of that research for the development of novel interventions to treat psychological disorders has been recognized only recently. Here we provide an overview of basic research and clinical studies

on emotional memory reconsolidation interference. We point out specific advantages of interventions based on memory reconsolidation interference over traditional treatment for emotional disorders. We also explain how findings from basic research suggest limitations and challenges to clinical translation that may help to understand why clinical trials have met with mixed success so far and how their success can be increased. In closing, we preview new intervention approaches beyond the induction of amnesia that the phenomenon of memory reconsolidation may afford for alleviating the burden imposed by emotional memories and comment on theoretical controversies regarding the nature of memory reconsolidation.

Extinction during memory reconsolidation blocks recovery of fear in adolescents


Mappe: anden Rec/2015 a

D. C. Johnson & B. J. Casey

Adolescence is a time of intensified emotional experiences, during which anxiety and stress-related disorders peak. The most effective behavioral therapies for treating these disorders share exposure-based techniques as a core component. Exposure-based therapies build on the principles of fear extinction learning and involve desensitizing the individual to cues that trigger anxiety. Yet, recent evidence shows an adolescent-specific diminished capacity to extinguish fear responses, suggesting that adolescents may respond less well to exposure-based therapies than other age groups. Here we demonstrate an alternative method for blocking the recall of fear memories in adolescents, building on principles of memory reconsolidation in adults. During memory reconsolidation, a memory that is recalled becomes labile during which time it can be updated. Prior research has shown that extinction training during memory reconsolidation attenuates the recovery of fear memory in human adults and in rodents. Using this method, we show attenuation of fear memory in adolescent humans. These findings have significant implications for treating one of the most vulnerable populations to anxiety and stress related disorders – adolescents – by optimizing exposure therapy based on principles of memory reconsolidation.

Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial

Mappe: Authors/Alain Brunet/2018 a

Alain Brunet, Ph.D., Daniel Saumier, Ph.D., Aihua Liu, Ph.D., David L. Streiner, Ph.D., Jacques Tremblay, M.D., Roger K. Pitman, M.D.

Objective: The authors assessed the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker, in reducing symptoms of posttraumatic stress disorder (PTSD).

Method:Thiswasa6-week,double-blind,placebo-controlled, randomized clinical trial in 60 adults diagnosed with longstanding PTSD. Propranolol or placebo was administered 90 minutes before a brief memory reactivation session, once a week for 6 consecutive weeks. The hypothesis predicted a significant treatment effect of trauma reactivation with propranolol compared with trauma reactivation with placebo in reducing PTSD symptoms on both the ClinicianAdministered PTSD Scale (CAPS) and the patient-rated PTSD Checklist–Specific (PCL-S) in an intention-to-treat analysis.

Results: The estimated group difference in posttreatment CAPS score, adjusted for pretreatment values (analysis of covariance), was a statistically significant 11.50. The within-group pre- to posttreatment effect sizes (Cohen’s d) were 1.76 for propranolol and 1.25 for placebo. For the PCL-S, the mixed linear model’s estimated time-by-group interaction yielded an average decrease of 2.43 points per week, for a total significant difference of 14.58pointsabovethatofplacebo.Thepre-toposttreatmenteffect sizes were 2.74 for propranolol and 0.55 for placebo. Per protocol analyses for both outcomes yielded similar significant results.

Conclusions: Pre-reactivation propranolol, a treatment protocol suggested by reconsolidation theory, appears to beanovel and efficacious treatment for PTSD. Replication studies using a long-termfollow up in various trauma populations are required.