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[Display omitted] The persistence of pathological memory is the basis of several psychiatric disorders. Memory retrieval induces "reconsolidation", a time interval during which the original memory becomes labile and destabilized. Time- and retrieval-dependent processes and memory reconsolidation are critical periods for memory interference. Modulating memory reconsolidation has received considerable research attention as a treatment protocol for several psychiatric conditions such as posttraumatic stress disorder, addiction, anxiety, and trauma-related disorders. This specific time window provides an opportunity for intervention regarding mental diseases. This article reviews the effect of modulating memory reconsolidation using behavioral-, brain stimulation-, and pharmacological-based interventions, which may help bridge the gap between intervention in laboratories and application in clinical practice. The potential advantages, limitations, challenges, and opportunities for memory reconsolidation manipulations were discussed. [ABSTRACT FROM AUTHOR]

Experiments demonstrating post-reactivation amnesia for learned fear in animals have generated a novel and influential hypothesis on the plasticity of memory, usually referred to as memory reconsolidation. The clinical potential of pharmacologically disrupting the process of memory reconsolidation has sparked a wave of interest into whether this phenomenon can also be demonstrated in humans, and ultimately harnessed for therapeutic purposes. In this essay we outline how the work of Karim Nader and colleagues has moved the field forward from a focus on extinction learning to the prospect of disrupting memory reconsolidation. We then review some promising findings on the necessary conditions, as well as potential boundary conditions, of pharmacologically disrupting the process of memory reconsolidation obtained in our laboratory. Even though laboratory experiments in animals and humans suggest that we may be at the brink of a breakthrough in fundamentally changing emotional memories, the necessary and sufficient conditions for targeting and disrupting memory reconsolidation in clinical practice are largely unknown. There is likely no universally effective reactivation procedure for triggering the reconsolidation of clinically significant emotional memories, and the impact of subtle boundary conditions observed in basic experiments compounds this issue. Notwithstanding these challenges, the discovery of changing emotional memory through disrupting the process of memory reconsolidation has unquestionably invigorated the field. [ABSTRACT FROM AUTHOR]

Current theoretical models of emotional processing rely mainly on detecting emotional processing through verbal, conscious, and cognitive processes. However, artmaking can potentially reveal embodied and implicit processes that may otherwise remain hidden in verbal expression. This paper attempts to close the scholarly gap by introducing a novel art-based emotional processing model that integrates emotional processing and art therapy literature, incorporating emotional meaning-making, awareness, acceptance, and memory consolidation. The art-based EP model explains the processes through which art creation may benefit emotional processing. It also elucidates the ways in which art therapy can be used to enhance therapeutic outcomes. • The proposed novel art-based emotional processing (EP) model closes a theory gap. • The model explains how art creation benefits EP. • Two art therapy cycles promote EP, by physical interaction with art materials. • Cycle 1 helps make sense of emotions and change dysfunctional EP patterns. • Cycle 2 helps memory reconsolidation for verbal/visual expression. [ABSTRACT FROM AUTHOR]

Background: Intrusive memories (IMs) of traumatic events are a key symptom of posttraumatic stress disorder (PTSD), and contribute to its maintenance. This translational proof-of-principle study tested whether a single-session behavioural intervention reduced the number of childbirth-related IMs (CB-IMs) and childbirth-related PTSD (CB-PTSD) symptoms, in women traumatised by childbirth. The intervention was assumed to disrupt trauma memory reconsolidation.Methods: In this pre-post study, 18 participants, whose traumatic childbirth had occurred between seven months and 6.9 years before, received an intervention combining childbirth-related reminder cues (including the return to maternity unit) with a visuospatial task. They recorded their daily CB-IMs in the two weeks pre-intervention (diary 1), the two weeks post-intervention (diary 2; primary outcome), and in week 5 and 6 post-intervention (diary 3). CB-PTSD symptom severity was assessed five days pre-intervention and one month post-intervention.Results: Compared to diary 1, 15/18 participants had ≥ 50% fewer CB-IMs in diary 2. The median (IQR) reduction of the number of CB-IMs was 81.89% (39.58%) in diary 2, and persisted in diary 3 (n = 17). At one month post-intervention, CB-PTSD symptom severity was reduced by ≥ 50% in 10/18 participants. Of the 8 participants with a CB-PTSD diagnosis pre-intervention, none met diagnostic criteria post-intervention. The intervention was rated as highly acceptable.Limitations: The design limits the causal interpretation of observed improvements.Conclusion: This is the first time such a single-session behavioural intervention was tested for old and real-life single-event trauma. The promising results justify a randomized controlled trial, and may be a first step toward an innovative CB-PTSD treatment. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder is a major public health problem and has a high rate of treatment resistance. Fear conditioning has been proposed as a potential mechanism sustaining negative affect in mood disorders. With the aim of exploring cognitive effects of rapid-acting antidepressant treatments as a potential mechanism of action that can be targeted by neuromodulation, we performed a narrative review of the extant literature on effects of electroconvulsive therapy, ketamine or esketamine, and sleep deprivation on emotional/fear memory retrieval-reconsolidation. We explore interference with reconsolidation as a potential common pathway that explains in part the efficacy of rapid-acting antidepressant treatments with disparate mechanisms of action. We propose the testable hypothesis that fear learning circuits can be specifically targeted by neuromodulation to attempt rapid amelioration of depressive symptoms (especially repetitive negative thinking) while limiting unspecific, untoward cognitive side effects. • Electroconvulsive therapy, ketamine, and sleep deprivation interfere with reconsolidation of emotional memories after retrieval. • Repetitive negative thinking can be conceptualized as a cycle of emotional memory retrieval-reconsolidation. • Emotional memory reconsolidation can be a direct target of neuromodulation in depression. [ABSTRACT FROM AUTHOR]

Pharmacologic and behavioral interventions that block reconsolidation of reactivated fear memory have demonstrated only limited success in modifying stronger and long-standing fear memories. Given the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) in treating PTSD, pursuit eye movements are a promising and novel intervention for studies of human memory reconsolidation. Here, we examined the efficacy of pursuit eye movements in interfering with reconsolidation of conditioned fear memories. We conducted a 3-day differential Pavlovian fear conditioning procedure in healthy adults, using videos of biologically prepared stimuli (tarantulas), partly reinforced with electrical shocks while recording skin conductance response (SCR) as a measure of autonomic conditioned responses. Fear conditioning was performed on Day 1. On Day 2, 38 participants were randomized into groups performing pursuit eye movements either immediately after fear memory reactivation, when the fear memory was stable, or 10 min later, when the fear memory was assumed to be more labile. On Day 3, fear memory strength was assessed by SCR to both reactivated and nonreactivated fear memories. Strong differential conditioning to the spider stimuli were observed during both fear acquisition and fear memory reactivation. Reactivated fear memory conditioned responses of participants performing pursuit eye movements after a 10-min delay were significantly smaller in the reinstatement phase (0.16 μS; 95% CI [0.02, 0.31]). Pursuit eye movements were effective in reducing fear-conditioned SCR in reinstatement. This result supports the theoretical proposition that EMDR can interfere with reactivated fear memory reconsolidation. • Pursuit eye movements 10min after reactivation of a conditioned fear memory reduce fear-conditioned skin conductance response • Pursuit eye movements, a core component of EMDR, may be effective in interfering reconsolidation of a reactivated fear memory • Eye movement effects may be one mechanism of successful EMDR treatment of traumatic fear memory in PTSD patients [ABSTRACT FROM AUTHOR]

Maladaptive emotional memories are a transdiagnostic feature of mental health problems. Therefore, understanding whether and how emotional memories can change might help to prevent and treat mental disorders. We tested whether neutral memories of naturalistic events can retroactively acquire positive or negative affect, in a preregistered three-day Modification of Valence in Episodes (MOVIE) paradigm. On Day 1, participants (N = 41) encoded memories of neutral movie scenes, representing lifelike naturalistic experiences. On Day 2, they retrieved each episode before viewing a happy, sad, or neutral scene from the same movie (yielding a within-subjects design with a neutral-negative, neutral-positive, and neutral-neutral condition). On Day 3, participants again retrieved each memory from Day 1. We assessed the affective tone of episodes through facial expressions of positive and negative affect (using facial electromyography, fEMG) and through self-reported feelings. Positive updating of neutral episodes led to increased expressions of positive affect, whereas negative updating led to increased self-reported negative feelings. These results suggest that complex neutral episodic memories can retroactively acquire an affective tone, but the effects were modest and inconsistent across affect readouts. Future research should investigate alternative approaches to updating emotional memories that produce more profound changes in the valence of memories. • We tested if neutral episodic memories can acquire positive or negative valence. • We developed a naturalistic three-day movie paradigm to investigate memory updates. • Positive updating increased positive affect measured with facial EMG. • Negative updating increased self-reported negative feelings. • Memory updating effects were modest and not consistent across emotion readouts. [ABSTRACT FROM AUTHOR]

• Memory reconsolidation impairment induces amnesia, developing over time. • Injections of protein synthesis inhibitors + reminder led to memory recovery. • Recovered memory can persist for more than 10 days. • Assumed that the reminder induces protein synthesis-dependent amnesia reactivation. • Suggested that amnesia, including its reactivation, is an active process. Memory recovery in amnestic animals is one of the most poorly studied processes. In this paper, we examine the role of protein synthesis and a reminder in the mechanisms of amnesia and memory recovery in grape snails trained to conditioned food aversion. Amnesia was induced by the impairment of memory reconsolidation using NMDA (N-methyl d -aspartate) glutamate receptor antagonists. In an early stage of amnesia (day 3), injections of protein synthesis inhibitors into animals combined with a reminder by a conditioned stimulus (CS) led to the recovery of aversive reactions to its presentation. Two types of changes in reactions to CS were revealed. In most animals, a persistent recovery of memory retrieval was found that lasted for at least 10 days. In other snails, aversive responses to CS persisted for 24 h. Isolated injections of inhibitors, injections of inhibitors and a reminder by the learning environment (without presenting a CS), usage of a differentiating stimulus instead of a CS, or inhibitor injections after the reminder did not affect the development of amnesia. The administration of protein synthesis inhibitors and a reminder in the late period after amnesia induction (10 days) did not affect its development or caused a short-term memory recovery. We suggest that amnesia is an active process that develops over time. The reminder induces the reactivation of the amnesia process dependent on protein synthesis, while the administration of protein synthesis inhibitors leads to the impairment of amnesia reactivation and recovery of the state formed before amnesia induction (i.e., recovery of conditioned food aversion memory). [ABSTRACT FROM AUTHOR]

• Memory engrams are dynamically modified in consolidation–reconsolidation processes. • Concepts of cell assembly and engram cell are different to reveal memory engrams. • Experimental strategies and background assumptions for future research are discussed. In this update article, we focus on "memory engrams", which are traces of long-term memory in the brain, and emphasizes that they are not static but dynamic. We first introduce the major findings in neuroscience and psychology reporting that memory engrams are sometimes diffuse and unstable, indicating that they are dynamically modified processes of consolidation and reconsolidation. Second, we introduce and discuss the concepts of cell assembly and engram cell, the former has been investigated by psychological experiments and behavioral electrophysiology and the latter is defined by recent combination of activity-dependent cell labelling with optogenetics to show causal relationships between cell population activity and behavioral changes. Third, we discuss the similarities and differences between the cell assembly and engram cell concepts to reveal the dynamics of memory engrams. We also discuss the advantages and problems of live-cell imaging, which has recently been developed to visualize multineuronal activities. The last section suggests the experimental strategy and background assumptions for future research of memory engrams. The former encourages recording of cell assemblies from different brain regions during memory consolidation–reconsolidation processes, while the latter emphasizes the multipotentiality of neurons and regions that contribute to dynamics of memory engrams in the working brain. [ABSTRACT FROM AUTHOR]

• Protein and RNA syntheses are necessary for amnesia induction. • The sensitivity of amnesia to retraining and reminders is reorganized over time. • Amnesia can be reactivated by a reminder presentation. • Late-stage amnesia that is resistant to retraining can be defined as specific anterograde amnesia. • The key characteristics of amnesia and memory formation are similar. According to a common perspective, amnesia is a passive consequence of memory consolidation or reconsolidation impairment. The results of our own study, as well as literature data, allowed us to offer an interpretation of amnesia. Amnesia is an active process whose key characteristics are similar to those of other long-term plastic rearrangements of the brain, including learning processes. In accordance with this hypothesis, the review considers the data we obtained on the mechanisms of amnesia induction and development caused by impairment of conditioned food aversion memory consolidation or reconsolidation. In particular, experimental data indicating the dependence of amnesia induction on protein and RNA syntheses are described. After amnesia induction, a time-dependent reorganization of its processes is shown to occur. In early amnesia stages (< 10 days), a gradual decrease in the possibility of memory formation during a second training was observed. In late stages of amnesia (10 days or more), an unusual physiological phenomenon was revealed—the second training did not lead to the formation of long-term memory. This effect was specific, as memory for a new type of food could possibly be formed in these animals. The described properties of amnesia facilitate its characterization as specific anterograde amnesia. In addition, at an early but not late amnesia stages, reminder presentation caused amnesia reactivation, impairment of which by DNA methyltransferase inhibitors caused memory recovery. The results obtained allow us to characterize amnesia as a specific, time-dependent, separate process. In conclusion, the potential biological significance of the described type of amnesia is considered, and we discuss the possible molecular mechanisms underlying it. [ABSTRACT FROM AUTHOR]

Memory reconsolidation is a process by which labile drug memories are restabilized in long-term memory stores, permitting their enduring control over drug-seeking behaviors. In the present study, we investigated the involvement of the dorsal raphé nuclei (DRN) in cocaine-memory reconsolidation. Sprague-Dawley rats (male, female) were trained to self-administer cocaine in a distinct environmental context to establish contextual drug memories. They then received extinction training in a different context. Next, the rats were re-exposed to the cocaine-predictive context for 15 min to reactivate their cocaine memories or remained in their home cages (no-reactivation control). Memory reactivation was sufficient to increase c-Fos expression, an index of neuronal activation, in the DRN, but not in the median raphé nuclei, during reconsolidation, compared to no reactivation. To determine whether DRN neuronal activity was necessary for cocaine-memory reconsolidation, rats received intra-DRN baclofen plus muscimol (BM; GABA B/A agonists) or vehicle microinfusions immediately after or 6 h after a memory reactivation session conducted with or without lever access. The effects of DRN functional inactivation on long-term memory strength, as indicated by the magnitude of context-induced cocaine seeking, were assessed 72 h later. Intra-DRN BM treatment immediately after memory reactivation with or without lever access attenuated subsequent context-induced cocaine-seeking behavior, independent of sex. Conversely, BM treatment in the adjacent periaqueductal gray (PAG) immediately after memory reactivation, or BM treatment in the DRN 6 h after memory reactivation, did not alter responding. Together, these findings indicate that the DRN plays a requisite role in maintaining cocaine-memory strength during reconsolidation. • Labile associative memories are maintained via a reconsolidation process. • DRN exhibits c-Fos expression during memory reconsolidation. • DRN inhibition during reconsolidation reduces cocaine-memory strength. [ABSTRACT FROM AUTHOR]

The most well known forms of "energy psychology" combine cognitive and exposure techniques with the stimulation of selected acupuncture points (acupoints) by tapping on them. Most clinicians who learn and utilize an acupoint tapping protocol integrate the approach within their existing clinical frameworks rather than using it as a stand-alone therapy. The method has been highly controversial, with its efficacy, purported speed, and explanatory models all questioned. Nonetheless, its utilization within clinical settings and as a self-help method has continued to expand since it was introduced more than three decades ago. This paper reviews the most salient criticisms of the method and presents research and empirically based theoretical constructs that address them. More than 100 peer-reviewed outcome studies-51 of which are randomized controlled trials-provide an evidential base for evaluating the claims and criticisms surrounding the approach. This review concludes that a growing body of evidence indicates that acupoint-based energy psychology protocols are rapid and effective in producing beneficial outcomes in the treatment of anxiety, depression, PTSD, and possibly other conditions. Mechanisms by which acupoint tapping might bring about these treatment outcomes are also proposed. [ABSTRACT FROM AUTHOR]

• Memory reconsolidation and updating occurs during retrieval. • Art based therapies are likely advantageous for MR processing. • A sample protocol illustrates the integration of arts psychotherapy and memory reconsolidation research. Novel and rewarding experiences can reconsolidate people's memories and recalibrate their reactions to past events. Memory reconsolidation (MR) is a positive process whereby as autobiographical memories are recalled, they return to a labile state, and can be either reinforced or updated before reconsolidation. Thus, updating fear-based memories with non-fearful information may lead to permanent reduction in automatic responses and lasting changes to distressing memories. During recall, both implicit and explicit memories may be updated. The arts therapies offer rewarding and creative access to nonverbal autobiographical memories, as well as mitigate habitual reactions. When informed by the neuroscience of MR, art therapy relational neuroscience (ATR-N) practices support therapeutic MR dynamics. In support of these theoretical claims, the relevant literature is reviewed and then illustrated by a MR-ATR-N trauma-based protocol. [ABSTRACT FROM AUTHOR]

Highlights • Repeated MOR treatments induced both sensitization and conditioned hyper-locomotion. • A low dose of APO given during reconsolidation eliminated MOR conditioning. • The same low dose of APO given after reconsolidation had no effect on MOR conditioning. Abstract Morphine has potent pro-dopamine effects that can be manifested as hyper-locomotion and these behavioral effects can undergo conditioning and sensitization. The aim of the present study was to assess whether an inhibitory dopaminergic post-trial treatment (0.05 mg/kg apomorphine) given during re-consolidation could reduce morphine conditioning. To induce conditioned morphine hyperactivity and control for morphine exposure, a paired/unpaired Pavlovian conditioning protocol was used. The morphine paired groups received morphine in the open-field test arena and the unpaired groups received the same morphine (10 mg/kg) treatments but in a different environment. The morphine treatments were administered once per day for 5 days. With repeated treatments, the paired morphine groups developed a sensitized hyper-locomotion response whereas the unpaired morphine groups did not differ from vehicle groups. Subsequently, the paired, unpaired and vehicle groups were given four daily non-drug 5 min conditioning tests. In these conditioning tests, the paired but not the unpaired and vehicle groups exhibited a conditioned locomotor stimulant response. These groups were subdivided into matched groups and received either vehicle or 0.05 mg/kg apomorphine either during re-consolidation immediately post-test or after re-consolidation 15 min post-test. In the immediate post-trial treatment groups, the morphine conditioned response in the paired group was eliminated after only one post-trial apomorphine treatment. The same immediate 0.05 mg/kg apomorphine post-trial treatments had no effect on the unpaired morphine or vehicle groups. In the paired group that received vehicle immediately post-trial, the conditioned response remained robust and unchanged over the four conditioning tests. In the post-trial 15 min delay treatment groups, the post-trial apomorphine treatments had no effect on the morphine conditioned response. These results showed that the inhibition of dopamine activity by apomorphine during the re-consolidation of a cue activated morphine conditioned response eliminated morphine conditioned effects. In that morphine conditioned effects are important for the initiation of addiction and in triggering drug craving and relapse, this finding has potential relevance to opioid addiction treatment. [ABSTRACT FROM AUTHOR]

Can mental imagery rather than external stimulation reactivate an aversive conditioned memory for the purposes of attenuating fear with subsequent extinction training? To answer this question participant underwent a three-day protocol: Day 1 entailed fear acquisition training in which two conditioned stimuli were paired with mild shock (US), while a CS- never was; day 2 included imagery-based reactivation of only one of the two CS+ followed by standard extinction training within the reconsolidation ten minutes later; day 3 included reinstatement by the unsignaled presentation of the US followed by a re-extinction phase. We observed no evidence of fear recovery on the first trial of re-extinction for the reminded, mentally imaged, CS+, whereas fear returned for the non-reminded CS+. Thus, mental imagery was sufficient to reactivate a fear memory thereby opening the reconsolidation window and facilitating fear suppression via extinction training. The clinical implications of this are potentially far-reaching as it allows for in vivo reconsolidation procedures in exposure therapy. [ABSTRACT FROM AUTHOR]

Abstract This investigation was undertaken to compare the sensitization/conditioned effects induced by apomorphine given pre-trial versus administered immediately post-trial or 15 min post-trial. We measured the effects on locomotor activity of 5 daily apomorphine treatments induced by an inhibitory low auto-receptor dose (0.05 mg/kg) and a stimulatory high postsynaptic dose (2.0 mg/kg). Three sets of four groups were used and each set of four groups was comprised of two vehicle and two apomorphine groups (0.05/2.0 apomorphine). The only difference among the three sets of four groups was when the treatments were administered relative to placement in the novel environment. One set received the treatment pre-test, another set was injected immediately after and the third set injected 15 min after 5 min test sessions in a novel environment. The repeated pre and immediate post-test apomorphine treatments induced locomotor sensitization over the 5 days of treatment. The low dose pre and immediate post-test treatments progressively decreased locomotion and the high dose pre and immediate post-test progressively increased locomotion. Critically, the tests for the immediate post-test groups were non-drug and for both the pre-test and immediate post-test groups, sensitization effects did not occur until the second test day. To control for non-associative apomorphine effects, the same apomorphine treatments were given post-test after a 15 minute delay and were found to be equivalent to vehicle. In a subsequent conditioning test, both the pre and immediate post-test low dose apomorphine groups showed conditioned behavioral inhibition and the pre and immediate post-test high dose apomorphine groups showed conditioned behavioral stimulation. We propose that the inhibitory low dose apomorphine decreased the salience/incentive of the novel environment association and thereby decreased the behavioral response and conversely that the high dose excitatory apomorphine treatment increased the salience/incentive value of the novel environment association and potentiated the behavioral response. Highlights • Repeated apomorphine treatment effects on behavior in a novel environment • Low and high dose apomorphine conditioned and sensitized locomotor effects • Similar sensitization effects of pre versus immediate post-trial apomorphine • Similar conditioned effects of pre versus immediate post-trial apomorphine • No conditioned or sensitization effects with delayed post-trial apomorphine [ABSTRACT FROM AUTHOR]

Highlights The results of an art therapy experimental study of the four-drawing trauma and resiliency protocol showed: • A decrease in overall effects of the traumatic event, negative affect, pain endorsement and possibly pain intensity. • An increase in the number of endorsed resources. • The drawings had a positive impact on participants' understanding and meaning-making of the traumatic event. Abstract Resiliency, as fostered by creativity, imagination, and the arts therapies, is a critical factor in managing the impact of adversity. This pilot study investigated the potential effectiveness of a four-drawing art therapy trauma and resiliency protocol for coping with adverse life events. The protocol is designed according to memory reconsolidation research and based in art therapy relational neuroscience (ATR-N) principles and trauma models. The hypotheses were that participation in the four-drawing protocol would result in: decreases in overall effect of the traumatic event (hypothesis one), decreases in negative affect endorsement and rating as expressed by sadness, grief, depression and anxiety (hypothesis two and three), reductions in pain endorsement and rating (hypothesis four and five), increases in resiliency-based resources (hypothesis six), positively rated impact on participants' understanding of the problem and resources (hypothesis seven), increases in posttraumatic growth cognitions (hypothesis eight), and increases in relational security (hypothesis nine). The positive effects of the four-drawing protocol components, including the drawings, questionnaires, and inquiry were examined. Main findings included significant decreases in the rating of the effect of the traumatic event (hypothesis one), self-reported endorsement and ratings of negative affect (hypothesis two and three), trends in pain reduction ratings (hypothesis five), significant increases in endorsed resiliency resources (hypothesis six), and positive ratings of the impact of the drawing activity (hypothesis seven), but no significant changes in endorsement of pain (hypothesis four), posttraumatic growth cognitions (hypothesis eight), or relational security (hypothesis nine). Additional results revealed that decreased endorsement and ratings of negative affect continued to be maintained at follow-up, and that the inquiry had a self-reported positive impact on participants' understanding and meaning-making of the traumatic event. It is possible that memory reconsolidation processes may account for the positive changes. [ABSTRACT FROM AUTHOR]

Abstract Epigenetic remodeling contributes to synaptic plasticity via modification of gene expression, which underlies cocaine-induced long-term memory. A prevailing hypothesis in drug addiction is that drugs of abuse rejuvenate developmental machinery to render reward circuitry highly plastic and thus engender drug memories to be highly stable. Identification and reversal of these pathological pathways are therefore critical for cocaine abuse treatment. Previous studies revealed an interesting finding in which the mRNA of histone lysine demethylase, KDM6B, is upregulated in the medial prefrontal cortex (mPFC) during early cocaine withdrawal. However, whether and how it contributes to drug-seeking behavior remain unknown. Here we used a conditioned place preference paradigm to investigate the potential role of KDM6B in drug-associated memory. We found that KDM6B protein levels selectively increased in the mPFC during cocaine withdrawal. Notably, systemic injection of KDM6B inhibitor, GSK-J4, disrupted both reconsolidation of cocaine-conditioned memory and cocaine-primed reinstatement, suggesting dual effects of KDM6B in cocaine reward memory. In addition, we found that NMDAR expression and function were both enhanced during early cocaine withdrawal in mPFC. Injection of GSK-J4 selectively reversed this cocaine-induced increase of NR2A expression and synaptic function, suggesting that mal-adaptation of cocaine-induced synaptic plasticity in mPFC largely underlies KDM6B-mediated cocaine-associated memory. Altogether, these data suggest that KDM6B plays an essential role in cocaine-associated memory, which mainly acts through enhancing cocaine-induced synaptic plasticity in the mPFC. Our findings revealed a novel role of KDM6B in cocaine-associated memory and inhibition of KDM6B is a potential strategy to alleviate drug-seeking behavior. Highlights • KDM6B protein is selectively increased in the mPFC during cocaine withdrawal. • Inhibiting KDM6B decreases cocaine-conditioned memory reconsolidation. • Inhibiting KDM6B attenuates cocaine-primed reinstatement. • Inhibiting KDM6B specifically blocks the NR2A expression and function. [ABSTRACT FROM AUTHOR]

There is increasing evidence that oxytocin is involved in learning and memory process. This study investigated the effects of blockade of oxytocin receptors using the selective oxytocin receptor antagonist atosiban (ATO) on contextual fear memory consolidation and reconsolidation in male rats. Post-training injections of different doses of ATO (1, 10, 100 or 1000 µg/kg) impaired the 48 h retention performance in a dose-dependent manner. The same doses of ATO following memory reactivation did not impair subsequent expression of contextual fear memories which formed under low or high shock intensities and tested 24 h or one week following memory reactivation. Also, no effect was found when ATO was administrated in the absence of memory reactivation. Our finding is the first report that indicates endogenous oxytocin released during training play an important role in the consolidation, but not reconsolidation of contextual fear memory in rats. [ABSTRACT FROM AUTHOR]

MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers. This review explores the potential role of memory reconsolidation and fear extinction during MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin, norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By reducing activation in brain regions implicated in the expression of fear- and anxiety-related behaviors, namely the amygdala and insula, and increasing connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing of traumatic memories and emotional engagement with therapeutic processes. Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1β (IL-1β) influences hippocampus-dependent memories. We previously reported that administration of IL-1β in dorsal hippocampus impaired contextual fear memory reconsolidation. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (α-MSH). Our results also demonstrated that IL-1β produced a significant decrease in glutamate release from dorsal hippocampus synaptosomes after reactivation of the fear memory. Therefore, we investigated whether IL-1β administration can affect GluA1 AMPA subunit phosphorylation, surface expression, and total expression during reconsolidation of a contextual fear memory. Also, we studied the modulatory effect of α-MSH. We found that IL-1β reduced phosphorylation of this subunit at Serine 831 and Serine 845 60 min after contextual fear memory reactivation. The intrahippocampal administration of IL-1β after memory reactivation also induced a decrease in surface expression and total expression of GluA1. α-MSH prevented the effect of IL-1β on GluA1 phosphorylation in Serine 845, but not in Serine 831. Moreover, treatment with α-MSH also prevented the effect of the cytokine on GluA1 surface and total expression after memory reactivation. Our results demonstrated that IL-1β regulates phosphorylation of GluA1 and may thus play an important role in modulation of AMPAR function and synaptic plasticity in the brain. These findings further illustrate the importance of IL-1β in cognition processes dependent on the hippocampus, and also reinforced the fact that α-MSH can reverse IL-1β effects on memory reconsolidation. [ABSTRACT FROM AUTHOR]

• This study examined whether delivering electroconvulsive therapy (ECT) during the reconsolidation of traumatic memories may enhance its efficacy in posttraumatic stress disorder (PTSD). • Delivering ECT after retrieving the traumatic memory enhanced the improvement of PTSD symptoms and the reduction of subjective reactivity to the traumatic memory. • Reduction in anxiety and mood symptoms and physiological reactivity to the traumatic memory were observed in the sample as a whole regardless of memory retrieval. Delivering electroconvulsive therapy (ECT) during the reconsolidation of traumatic memories may enhance the treatment efficacy in posttraumatic stress disorder (PTSD). To test this, 14 patients with severe and refractory PTSD were randomly allocated to receive ECT sessions either after retrieving the traumatic (n=8) or a neutral (n=6) memory. We found that delivering ECT after retrieving the traumatic memory enhanced the improvement of PTSD symptoms and the reduction of subjective reactivity to the traumatic memory. Reduction in anxiety and mood symptoms and physiological reactivity to the traumatic memory were observed in the sample as a whole regardless of memory retrieval. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that when a memory is reactivated through retrieval, it becomes temporarily vulnerable to environmental or pharmacological manipulation, which can consequently update or strengthen the memory. Physical exercise has been shown to modulate the maintenance of fear memories in animals following memory reactivation. This study investigated the effect of intense exercise in modulating the reconsolidation of trauma memories. Fifty-four undergraduate students watched a trauma film depicting the aftermath of a highway car crash. Two days later, participants engaged in either (a) 20–25 min of incremental cycling following a memory reactivation induction (Reactivation/Exercise), (b) 20–25 min of mild cycling (Reactivation/No Exercise) following memory reactivation, or (c) 20–25 min of incremental cycling but no memory reactivation (No Reactivation/Exercise). Saliva samples were collected to index salivary amylase and cortisol at baseline and post activity. Participants completed memory questionnaires relating to declarative and intrusive memory recall two days after memory reactivation. Reactivation/Exercise participants recalled more central details of the trauma film relative to other participants. Increased cortisol predicted better total memory recall in the Reactivation/Exercise, but not in the other conditions. These findings suggest that intense exercise during the period of memory reactivation enhances subsequent trauma memory, and provides human evidence consistent with recent findings of exercise-induced fear reconsolidation in animals. [ABSTRACT FROM AUTHOR]

In normal settings, our brain is able to update its stored representations in content, strength, and/or expectations by the memory reconsolidation process. Thus, a reactivated memory enters in a transient labile state (destabilization) followed by a re-stabilization phase in order to persist (memory reconsolidation). Cognitive neuroscience and its insight into psychiatric problems attributed a close relationship between memory (formation, maintenance, and utilization) and several mental disorders. In this framework, the reconsolidation process could be not only the mechanism for maintenance of some psychopathologies, but also open a novel therapeutic window. Here we aim to integrate recent experimental and theoretical research on memory reconsolidation and anxiety disorders maintenance. We propose a bayesian-like model about anxiety disorders persistence and postulate a new theoretical framework for how anxiety disorders are maintained through impaired memory updating due to a dysfunctional prediction error minimization strategy and anticipatory responses to threat. [ABSTRACT FROM AUTHOR]

Background Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During EMDR, patients make horizontal eye movements (EMs) while simultaneously recalling a traumatic memory, which renders the memory less vivid and emotional when it is later recalled again. Recalling highly emotional autobiographical memories enhances noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory (re)consolidation. However, memories become less vivid after recall+EMs. Therefore, NA might either play no significant role or serve to strengthen memories that are degraded by EMs. The present study was designed to test the latter hypothesis. We predicted that blocking NA would abolish the memory degrading effects of EMs. Methods Fifty-six healthy participants selected three negative autobiographical memories. One was then recalled while making EMs, one was recalled without EMs, and one was not recalled. Vividness and emotionality of the memories as well as heart rate and skin conductance level during memory retrieval were measured before, directly after, and 24 hours after the EM task. Before the task, participants received a placebo or the noradrenergic β-receptor blocker propranolol (40 mg). Results There were no effects of EMs on memory emotionality or psychophysiological measures in the propranolol and placebo groups. However, in the placebo group, but not in the propranolol group, memory vividness significantly decreased from pretest to posttest and follow-up after recall+EMs relative to the control conditions. Conclusions Blocking NA abolished the effects of EMs on the vividness of emotional memories, indicating that NA is crucial for EMDR effectiveness and possibly strengthens the reconsolidation of the degraded memory. [ABSTRACT FROM AUTHOR]

The basolateral amygdala (BLA) is a critical site for the reconsolidation of labile contextual cocaine memories following retrieval-induced reactivation/destabilization. Here, we examined whether glucocorticoid receptors (GR), which are abundant in the BLA, mediate this phenomenon. Rats were trained to lever press for cocaine reinforcement in a distinct environmental context, followed by extinction training in a different context. Rats were then briefly exposed to the cocaine-paired context (to elicit memory reactivation and reconsolidation) or their home cages (no reactivation control). Exposure to the cocaine-paired context elicited greater serum corticosterone concentrations than home cage stay. Interestingly, the GR antagonist, mifepristone (3–10 ng/hemisphere), administered into the BLA after memory reactivation produced a further, dose-dependent increase in serum corticosterone concentrations during the putative time of cocaine-memory reconsolidation but produced an inverted U-shaped dose-effect curve on subsequent cocaine-seeking behavior 72 h later. This effect was anatomically selective, dependent on memory reactivation (i.e., not observed after home cage exposure), and did not reflect protracted hyperactivity. However, the effect was also observed when mifepristone was administered after novelty stress that mimics drug context-induced hypothalamic-pituitary-adrenal (HPA) axis activation without explicit memory reactivation. Together, these findings suggest that, similar to explicit memory retrieval, a stressful event is sufficient to destabilize cocaine memories and permit their manipulation. Furthermore, BLA GR stimulation exerts inhibitory feedback upon HPA axis activation and thus suppresses cocaine-memory reconsolidation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Consolidated memories become labile upon reactivation and as a result have to go through reconsolidation to become re-stabilized. This property of memory may potentially be used to reduce the impact of highly negative episodic memories. Because detailed and vivid negative memories are mediated by high arousal, if arousal is lessened during reconsolidation, memory accuracy and vividness should diminish. In this study, we examined this hypothesis.Methods: Participants (N = 72) viewed a stressful, suspenseful video on Day 1 to develop negative episodic memories. Then, 24-29 h later, they saw a brief reminder of the stressful video (or not), and then viewed a neutral, calming (or positive) video. Another 24-29 h later, participants were tested on the accuracy, vividness, and anxiety associated with their memory of the stressful video on Day 1.Results: Participants who watched the reminder and then the neutral video showed reduced memory accuracy compared to participants in the other groups. Despite the reduction in memory accuracy, their memory vividness and anxiety associated with the stressful video did not decrease.Limitations: The use of undergraduates prevents generalizations to clinical populations. Also, the study did not test long-term memories that were more than 2 days old.Conclusions: Neutral mood induction during reconsolidation reduces the accuracy of highly negative episodic memories. [ABSTRACT FROM AUTHOR]

Memories are not set forever, but can be altered following reactivation, which renders memories malleable, before they are again stabilized through reconsolidation. Fear memories can be attenuated by using extinction during the malleable period. The present study adopts a novel form of extinction, using verbal instructions, in order to examine whether fear memory reconsolidation can be affected by an imaginal exposure. The extinction using verbal instructions, called imaginal extinction, consists of a recorded voice encouraging participants to imagine the scene in which fear was acquired, and to envision the stimuli before their inner eye. The voice signals stimuli appearance, and identical to standard (in vivo) extinction, participants discover that the conditioned stimulus no longer is followed by unconditioned stimulus (UCS). In this way, imaginal extinction translates clinically used imaginal exposure into the standard experimental fear conditioning paradigm. Fear was acquired by pairing pictorial stimuli with an electric shock UCS. Then, both standard and imaginal extinction were given following fear memory reactivation, either after 10 min, within the reconsolidation interval, or after 6 h, outside of the reconsolidation interval. In vivo and imaginal extinction produced comparable reductions in conditioned responses during extinction and importantly, both disrupted reconsolidation of conditioned fear and abolished stimulus discrimination between reinforced and non-reinforced cues. Thus, disrupted reconsolidation of fear conditioning can be achieved without in vivo stimulus presentation, through purely cognitive means, suggesting possible therapeutic applications. [ABSTRACT FROM AUTHOR]

Continual relation extraction techniques aim to meet the requirements of real-world applications, in which new data and relations emerge constantly. To strike a balance between continual learning ability and computational cost, many previous works on replay-based methods emphasized on employing different strategies to use a smaller number of stored replay samples to maintain the continual ability of the model. However, catastrophic forgetting is prone to occur if a limited number of previously stored replay samples have been used. In this paper, we proposed a continual learning method which contains three learning phases, namely preliminary learning, memory retention, and memory reconsolidation. In more detail, the model is fine-tuned on the model of the last previous task firstly in the preliminary learning stage. During the memory retention stage, the method utilizes the characteristics of the model's linear mode connectivity between the multi-task learning model and the continual learning model to retain the knowledge of previous tasks as much as possible. At the memory reconsolidation stage, it uses the previously stored samples as well as the ones of the current task for interval cross training to reconsolidate the learned knowledge. In order to evaluate the continual learning ability of the model learning by the proposed method, we tested it on three well-studied benchmarks, and the experimental results show that our algorithm performs better than the other compared algorithms in terms of the average accuracy as well as overall accuracy. [ABSTRACT FROM AUTHOR]

The study of the amnesia mechanisms is of both theoretical and practical importance. The mechanisms of anterograde amnesia are the least studied, due to the lack of an experimental model that allows studying this amnesia type molecular and cellular mechanisms. Previously, we found that conditional food aversion memory reconsolidation impairment in snails by NMDA glutamate receptor antagonists led to the amnesia induction, in the late stages of which (>10 days) repeated training did not cause long-term memory formation. In the same animals, long-term memory aversion to a new food type was formed. We characterized this amnesia as specific anterograde amnesia. In the present work we studied the role of epigenetic DNA methylation processes as well as protein and mRNA synthesis in the mechanisms of anterograde amnesia and memory recovery. DNMT methyltransferase inhibitors (iDNMT: zebularine, RG108 (N-Phthalyl-1-tryptophan), and 5-AZA (5-Aza-2'-deoxycytidine)) were used to alter DNA methylation. It was found that in amnesic animals the iDNMT administration before or after shortened repeated training led to the rapid long-term conditional food aversion formation (Ebbinghaus saving effect). This result suggests that amnestic animals retain a latent memory, which is the basis for accelerated memory formation during repeated training. Protein synthesis inhibitors administration (cycloheximide) before or immediately after repeated training or administration of RNA synthesis inhibitor (actinomycin D) after repeated training prevented memory formation under iDNMT action. The earlier protein synthesis inhibitor effect suggests that the proteins required for memory formation are translated from the pre-existing, translationally repressed mRNAs. Thus, we have shown for the first time that the anterograde amnesia key mechanism is DNMT-dependent suppression of the transcription of genes involved in memory mechanisms. Inhibition of DNMT during repeated training reversed these genes expression blockade, opening access to them by transcription factors synthesized during training from the pre-existing mRNAs. • Memory reconsolidation impairment leads to anterograde amnesia development. • Retraining of amnestic grape snails did not induce long-term memory formation. • DNA methyltransferase inhibitor (iDNMT)+retraining induced memory formation. • The effect of iDNMT on memory formation depended on protein and RNA synthesis. • DNA methylation-dependent gene repression underlies the anterograde amnesia. [ABSTRACT FROM AUTHOR]

The mechanisms underpinning the persistence of emotional memories are inaccurately understood. Advancing the current level of understanding with regards to this aspect is of potential translational value for the treatment of post-traumatic stress disorder (PTSD), which stems from an abnormal aversive memory formation. Tamoxifen (TMX) is a drug used in chemotherapy for breast cancer and associated with poor cognitive performances. The present study investigated whether the systemic administration of TMX (1.0–50 mg/kg) during and/or beyond the reconsolidation time-window could attenuate a reactivated contextual fear memory in laboratory animals. When administered 0, 6 or 9 h (but not 12 h) post-memory retrieval and reactivation, TMX (50 mg/kg) reduced the freezing behavior in male rats re-exposed to the paired context on day 7, but not on day 1, suggesting a specific impairing effect on memory persistence. Importantly, this effect lasts up to 21 days, but it is prevented by omitting the memory retrieval or memory reactivation. When female rats in the diestrous or proestrous phase were used, the administration of TMX 6 h after retrieving and reactivating the fear memory also impaired its persistence. Altogether, regardless of the gender, the present results indicate that the TMX is able to disrupt the persistence of reactivated fear memories in an expanded time-window, which could shed light on a new promising therapeutic strategy for PTSD. [ABSTRACT FROM AUTHOR]

The ability to make predictions based on stored information is a general coding strategy. A Prediction-Error (PE) is a mismatch between expected and current events. It was proposed as the process by which memories are acquired. But, our memories like ourselves are subject to change. Thus, an acquired memory can become active and update its content or strength by a labilization-reconsolidation process. Within the reconsolidation framework, PE drives the updating of consolidated memories. Moreover, memory features, such as strength and age, are crucial boundary conditions that limit the initiation of the reconsolidation process. In order to disentangle these boundary conditions, we review the role of surprise, classical models of conditioning, and their neural correlates. Several forms of PE were found to be capable of inducing memory labilization-reconsolidation. Notably, many of the PE findings mirror those of memory-reconsolidation, suggesting a strong link between these signals and memory process. Altogether, the aim of the present work is to integrate a psychological and neuroscientific analysis of PE into a general framework for memory-reconsolidation. [ABSTRACT FROM AUTHOR]

Memory reconsolidation processes and protein kinase Mzeta (PKMzeta) activity in memory maintenance and reorganization are poorly understood. Therefore, we examined memory reconsolidation and PKMzeta activity during the maintenance and reorganization of a conditioned food aversion memory among snails. These processes were specifically evaluated after administration of a serotonin receptor antagonist (methiothepin), NMDA glutamate receptor antagonist (MK-801), protein synthesis inhibitor (cycloheximide; CYH), or PKMzeta inhibitor (zeta inhibitory peptide; ZIP) either 2 or 10 days after aversion training. Two days post-training, injections of MK-801 or CYH, combined with a conditioned stimulus reminder, caused amnesia development, and a second training 11 days after this induction did not lead to long-term memory formation. Interestingly, MK-801 or CYH injections and the reminder 10 days after training did not affect memory retrieval. Methiothepin and the reminder, or ZIP without the reminder, at 2 and 10 days after training led to memory impairment, while a second training 11 days after amnesia induction resulted in memory formation. These results suggest that the maintenance of a conditioned food aversion involves two different components with variable dynamics. One component could be characterized by memory strengthening over time and involve N -methyl- D -aspartate receptors and protein synthesis reconsolidation at early, but not late, training stages. The other memory component could involve serotonin-dependent reconsolidation and Mzeta-like kinase activity at both early and late stages after learning. Deficiencies within these two components led to various forms of memory impairment, which differed in terms of the formation of a conditioned food aversion during the second training. [ABSTRACT FROM AUTHOR]

Background: The reconsolidation blocker propranolol abolishes alcohol and drug-seeking behavior in rodents and attenuates conditioned emotional responses to drug-cues in humans in experimental settings. This suggests a role for its use in the treatment of substance dependence. In this translational pilot study, we explored the feasibility and efficacy of this procedure as an adjunct treatment for addiction. We hypothesized that guided addiction-related memory reactivation under propranolol would significantly attenuate tonic craving, a central element in relapse following addiction treatment.Methods: Seventeen treatment-seeking adults diagnosed with substance dependence were randomized to receive double-blind propranolol (n = 9) or placebo (n = 8) on six occasions prior to reading a personalized script detailing a drug-using experience. The primary outcome measure was self-reported craving intensity.Results: After controlling for baseline craving scores, intent-to-treat analysis revealed a time by group interaction, F(1, 14) = 5.68, p = .03, η(2) = 0.29; craving was reduced in the propranolol-treated group (Cohen's d = 1.40, p < .05) but not in the placebo group (d = 0.06, n.s.).Limitations: The usual limitations related to small sample size and the lack of a follow-up apply here.Conclusion: Drug-related memory reactivation under propranolol can subsequently reduce craving among substance-dependent individuals. Considering the relapse rate among individuals treated for substance dependence, our study highlights the feasibility of, and need for, more comprehensive trials of this treatment approach. [ABSTRACT FROM AUTHOR]

Reactivation of consolidated memory initiates a memory reconsolidation process, during which the reactivated memory is susceptible to strengthening, weakening or updating. Therefore, effective interference with the memory reconsolidation process is expected to be an important treatment for drug addiction. The nucleus accumbens (NAc) has been well recognized as a pathway component that can prevent drug relapse, although the mechanism underlying this function is poorly understood. We aimed to clarify the regulatory role of the NAc in the cocaine memory reconsolidation process, by examining the effect of applying different pharmacological interventions to the NAc on Zif 268 and Fos B expression in the entire reward circuit after cocaine memory reactivation. Through the cocaine-induced conditioned place preference (CPP) model, immunohistochemical and immunofluorescence staining for Zif 268 and Fos B were used to explore the functional activated brain nuclei after cocaine memory reactivation. Our results showed that the expression of Zif 268 and Fos B was commonly increased in the medial prefrontal cortex (mPFC), the infralimbic cortex (IL), the NAc-core, the NAc-shell, the hippocampus (CA1, CA2, and CA3 subregions), the amygdala, the ventral tegmental area (VTA), and the supramammillary nucleus (SuM) following memory reconsolidation, and Zif 268/Fos B co-expression was commonly observed (for Zif 268: 51–68%; for Fos B: 52–66%). Further, bilateral NAc-shell infusion of MK 801 and SCH 23390, but not raclopride or propranolol, prior to addictive memory reconsolidation, decreased Zif 268 and Fos B expression in the entire reward circuit, except for the amygdala, and effectively disturbed subsequent CPP-related behavior. In summary, N-methyl- d -aspartate (NMDA) and dopamine D 1 receptors, but not dopamine D 2 or β adrenergic receptors, within the NAc-shell, may regulate Zif 268 and Fos B expression in most brain nuclei of the reward circuit after cocaine memory reactivation. These findings indicated that the NAc played a key role in regulating addictive memory reconsolidation by influencing the function of the entire addictive memory network. [ABSTRACT FROM AUTHOR]

Reconsolidation has been defined as the process of memory stabilization after retrieval involving, among others, gene expression regulation and post-translational modifications. Many of these mechanisms are shared with memory consolidation. Here, we studied hippocampal ERK participation on memory reconsolidation of an inhibitory avoidance task in CF-1 mice. We found a retrieval-induced cytosolic ERK2 activation in the hippocampus (HIP) 15 min after memory reactivation, and an inhibition at 45 min. PD098059, a MEK1/2 (MAPK/ERK kinase) inhibitor, administered in the HIP immediately after retrieval impaired memory in a dose-dependent fashion. However, infusions of the highest dose of PD098059 performed 40 min after retrieval enhanced memory in mice trained with a weaker footshock. These results suggest for the first time that ERK2 is involved in memory reconsolidation in a biphasic fashion. Furthermore, the inhibition of ERK could either impair or enhance mice performance depending on ERK state of activation. [ABSTRACT FROM AUTHOR]

This article reports on a qualitative one-year follow-up for participants from an art therapy pain protocol study (Hass-Cohen et al., 2021). The purpose of the current study was to describe participants' long-term outcomes related to their pain experiences and quality of life, and to identify potential therapeutic memory reconsolidation (MR) change factors. Four semi-structured interviews and response drawings were conducted with participants from the pain protocol study. For the current follow-up study, an inductive analysis of the interview transcripts and response drawings were reported as unique case outcomes and common themes. Positive outcomes included: less physiological pain, psychological and skill-based changes in pain, and more access to coping resources. Art therapy-based MR change factors were also identified, which included creative processes and protocol sequencing. • One-year follow-up qualitative study on an art therapy drawing pain protocol. • Outcomes included reductions in pain and increased access to coping resources. • Creative processes and sequencing of drawing prompts were reported as helpful. • Memory reconsolidation factors were creativity and visuospatial characteristics. • Memory reconsolidation was associated with secondary positive appraisal of coping. [ABSTRACT FROM AUTHOR]

Internal mechanisms of lasting therapeutic change have eluded empirical identification despite decades of outcome research. A breakthrough may be at hand in neurobiological research on memory reconsolidation (MR), which has identified (a) a fundamental mechanism of the brain capable of targeted, profound unlearning and nullification of subcortical emotional learnings and the behaviors and states of mind they generate, and (b) the specific experiences required by the brain for such unlearning. We review the empirically identified process of annulment of emotional learnings, show that it fulfills clinical theorists' criteria for a mechanism of change, and define an empirical study to validate or falsify this MR mechanism's hypothesized clinical occurrence and causal role in therapeutic change. Extensive preliminary clinical observations of transformational change, also described, strongly support the causal role of the mechanism. The MR framework could significantly advance psychotherapy effectiveness and unification, and resolve longstanding clinical conundrums and controversies. [ABSTRACT FROM AUTHOR]

Central cholinergic system is critically involved in all known memory processes. Endogenous acetylcholine release by cholinergic neurons is necessary for modulation of acquisition, encoding, consolidation, reconsolidation, extinction, retrieval and expression. Experiments from our laboratory are mainly focused on elucidating the mechanisms by which acetylcholine modulates memory processes. Blockade of hippocampal alpha-7-nicotinic receptors (α7-nAChRs) with the antagonist methyllycaconitine impairs memory reconsolidation. However, the administration of a α7-nAChR agonist (choline) produce a paradoxical modulation, causing memory enhancement in mice trained with a weak footshock, but memory impairment in animals trained with a strong footshock. All these effects are long-lasting, and depend on the age of the memory trace. This review summarizes and discusses some of our recent findings, particularly regarding the involvement of α7-nAChRs on memory reconsolidation. [ABSTRACT FROM AUTHOR]

The reconsolidation hypothesis posits that the presentation of a specific cue, previously associated with a life event, makes the stored memory pass from a stable to a reactivated state. In this state, memory is again labile and susceptible to different agents, which may either damage or improve the original memory. Such susceptibility decreases over time and leads to a re-stabilization phase known as reconsolidation process. This process has been assigned two biological roles: memory updating, which suggests that destabilization of the original memory allows the integration of new information into the background of the original memory; and memory strengthening, which postulates that the labilization-reconsolidation process strengthens the original memory. The aim of this review is to analyze the strengthening as an improvement obtained only by triggering such process without any other treatment. In our lab, we have demonstrated that when triggering the labilization-reconsolidation process at least once the original memory becomes strengthened and increases its persistence. We have also shown that repeated labilization-reconsolidation processes strengthened the original memory by enlarging its precision, and said reinforced memories were more resistant to interference. Finally, we have shown that the strengthening function is not operative in older memories. We present and discuss both our findings and those of others, trying to reveal the central role of reconsolidation in the modification of stored information. [ABSTRACT FROM AUTHOR]

The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction. [ABSTRACT FROM AUTHOR]

Abstract: Long–Evans rats downshifted from 32% to 4% sucrose solution exhibit lower consummatory behavior during downshift trials than rats exposed only to 4% sucrose. In Experiment 1, this effect, called consummatory successive negative contrast (cSNC), was attenuated by administration of the benzodiazepine anxiolytic chlordiazepoxide (CDP, 5mg/kg, ip) before the second downshift trial (Trial 12), but was not affected when CDP was administered before the first downshift trial (Trial 11). In Experiment 2, CDP administered after Trial 11 actually enhanced the cSNC effect on Trial 12. This posttrial effect of CDP was reduced by delayed administration (Experiment 3). This CDP effect was not present in the absence of incentive downshift (Experiments 4–5), or when animals were tested with the preshift incentive (Experiment 6) or after complete recovery from cSNC (Experiment 7). The posttrial CDP effect was observed after an 8-day interval between Trials 11 and 12 (Experiment 8) and when administered after Trial 12, rather than Trial 11 (Experiment 9). Experiment 10 extended the effect to Wistar rats. Because CDP is a memory interfering drug, it was hypothesized that its posttrial administration interferes with the consolidation of the memory of the downshifted incentive, thus prolonging the mismatch between expected (32% sucrose) and obtained (4% sucrose) incentives that leads to the cSNC effect. [Copyright &y& Elsevier]

Highlights: [•] We investigated the effects of Aβ 25–35 and lithium on object recognition memory reconsolidation. [•] Aβ impairs recognition memory only when is infused in the post-reactivation period. [•] Lithium prevents the negative effects of Aβ on memory reconsolidation. [•] Disturbances in the memory reconsolidation may play a role in Alzheimer's dementia. [ABSTRACT FROM AUTHOR]

Abstract: The alpha-1 adrenergic antagonist prazosin has been used to alleviate the symptoms of PTSD, but the mechanism remains unclear. One possibility is that prazosin may disrupt fear memory reconsolidation, leading to attenuation of fear responses. To test this hypothesis, we administered a single systemic injection of prazosin during the reconsolidation of olfactory fear conditioning in rats. We found that a post-retrieval injection of prazosin disrupted subsequent retrieval of fear. Similarly, intra-prelimbic cortex infusion of prazosin during the reconsolidation period also disrupted subsequent retrieval of fear. These findings suggest that fear memory undergoes reconsolidation through activation of alpha-1 adrenergic receptors in the prelimbic cortex. [Copyright &y& Elsevier]

Abstract: In contrast to neutral events, emotionally arousing events often are remembered vividly and with great detail. Although generally adaptive to survival, this emotional memory enhancement may contribute to psychopathology. Blocking the arousal-related noradrenergic activity with a β blocker shortly after learning prevents the emotional enhancement of memory. In the present experiment, we tested in 48 healthy subjects whether the administration of the β blocker propranolol before the reactivation of already consolidated emotional episodic memories may interfere with their reconsolidation and, thus, reduce the subsequent feeling of remembering associated with these memories. Our results show that propranolol before reactivation abolished the superior memory for emotional relative to neutral stimuli and decreased ‘remember’ judgments for emotional items, suggesting that β-adrenergic blockade during reactivation made emotional memories comparable to neutral memories. [Copyright &y& Elsevier]

Abstract: Memory allows organisms to predict future events based on prior experiences. This requires encoded information to persist once important predictors are extracted, while also being modifiable in response to changes within the environment. Memory reconsolidation may allow stored information to be modified in response to related experience. However, there are many boundary conditions beyond which reconsolidation may not occur. One interpretation of these findings is that the event triggering memory retrieval must contain new information about a familiar stimulus in order to induce reconsolidation. Presently, the mechanisms that affect the likelihood of reconsolidation occurring under these conditions are not well understood. Here we speculate on a number of systems that may play a role in protecting memory from being destabilized during retrieval. We conclude that few memories may enter a state in which they cannot be modified. Rather, metaplasticity mechanisms may serve to alter the specific reactivation cues necessary to destabilize a memory. This might imply that destabilization mechanisms can differ depending on learning conditions. [Copyright &y& Elsevier]

Abstract: Subjects exposed to learning experiences could store the new information through memory consolidation process. If consolidation is interfered by exposing the experimental subjects to another novel stimulus, memory of the first learning situation is sometimes disrupted. The cholinergic system is critically involved in acquisition of new information. Here, we use low doses of the muscarinic cholinergic receptor antagonist scopolamine (SCOP) to disrupt acquisition of new information, but sparing memory consolidation of previous memories. Mice were consecutively exposed to two learning situations: the inhibitory avoidance (IA) and the nose-poke habituation (NPH) tasks. The exposure of mice to the NPH task, after being trained in the IA apparatus, impairs consolidation of the avoidance memory in a manner related to the duration of the exposure to the NPH task. If the exposure to the NPH task occurred after reactivation of the avoidance memory, reconsolidation was impaired. Blockade of acquisition of the NPH task by SCOP allowed consolidation and reconsolidation of the avoidance memory. Results indicate that cholinergic system blockade by SCOP impairs acquisition but is less able to affect memory consolidation. The mere exposure and perception of a novel situation are not sufficient conditions to cause impairment of retention performance about previously learned information, but effective processing leading to acquisition of the NPH task information is necessary to cause the interference between both learning situations. [ABSTRACT FROM AUTHOR]

Abstract: Retrieval of a consolidated memory triggers a number of processes which depend, among other factors, on the duration of the reactivation session: reconsolidation requires a brief reactivation session, and extinction, a prolonged one. The scope of this study is to explore the potential role of the hippocampal endocannabinoid system on reconsolidation and extinction processes. Bilateral infusion of the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) into the CA1 region of the dorsal hippocampus of Wistar rats after memory reactivation facilitated the reconsolidation of the contextual fear conditioning memory. The inhibition of protein synthesis with DRB in the same brain region blocked memory reconsolidation. Both effects were persistent, lasting up to 7 days after the first retrieval experience. In contrast, the local infusion of anandamide blocked memory reconsolidation, an effect that was antagonized by the combined administration of anandamide with a subthreshold dose of a CB1 antagonist, supporting a CB1-mediated role of the hippocampal endocannabinoid system in the modulation of the memory reconsolidation. Local infusion of AM251 into CA1 blocked memory extinction whereas the administration of anandamide facilitated it; however, when combined with a subthreshold concentration of the CB1 antagonist, anandamide did not affect the extinction process. The clear-cut, opposite effects observed in each situation suggest a possible role of the hippocampal endocannabinoid system as a switching mechanism deciding which processes will take place, either maintaining the original memory (reconsolidation) or promoting a new learning (extinction). [Copyright &y& Elsevier]

Abstract: Well-consolidated fear-related memories, once retrieved, are susceptible to disruption and require reconsolidation in order to be maintained. We examined whether reactivated reward-related memories are also susceptible to interference by evaluating the effect of propranolol (PROP), a β-adrenergic antagonist known to impair reconsolidation of fear-related memories, on context-induced sucrose seeking. PROP administration upon reactivation reduced sucrose seeking behaviour 3 weeks post-training, indicating that reconsolidation of reward-related memories can be disrupted after a long post-training interval. [Copyright &y& Elsevier]

Abstract: Although reconsolidation of memory after reminder does not seem to be the simple reiteration of the sequential stages occurring during memory consolidation, both phenomena probably employ similar mechanisms including activation of glutamate receptors and protein synthesis. It is known that group I metabotropic glutamate receptors (mGluRs) are involved in memory consolidation and modulation of protein synthesis. The aim of present study was to investigate the role of mGluR5 in memory consolidation and reconsolidation and to determine whether inhibition of these receptors may affect protein synthesis in these processes. The one-trial passive avoidance task on chicks was used as the experimental model of learning. Injection of the mGluR5 antagonist MPEP into a specific chick brain region IMM resulted in amnesia, provided the injection was made either shortly before or after training, or approximately 4h after training. This amnesia was permanent, resembling the effects of protein synthesis inhibitors. MPEP injection immediately after reminder resulted in only a transient amnesia revealed 1h later. Increased expression of Zif/268 and c-Fos proteins 2h after initial training was abolished bilaterally in chicks injected with MPEP. Injection of MPEP immediately after reminder did not inhibit c-Fos and Zif/268 expression, on the contrary, their expression was increased, specifically in left IMM and was similar to that observed after initial training. These results show that at least in the chick model mGluR5 play an important role in both consolidation and reconsolidation of memory but the mechanisms triggered by their activation in these processes differ. It is suggested that Ca2+ signal derived from mGluR5 stimulation is necessary for complete memory consolidation, whereas during reconsolidation other mGluR5 triggered mechanisms of protein synthesis activation and regulation may be involved. [Copyright &y& Elsevier]