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Terrestrial gastropods have evolved new structures in the nervous system compared to marine and aquatic snails in order to adapt to their new habitat. The behavior of these animals is qualitatively different from the behavior of aquatic gastropods and includes not only the possibility of active interaction with other animals but also the demonstration of interest by active approach, avoidance, or escape in certain cases. The "arrow of love" used in copulation is unique to nature. Almost all types of associative memory can be formed in these animals, consolidation and reconsolidation of memory can be demonstrated, and mechanisms of memory maintenance and modification can be analyzed. At the level of functionally identified neurons and neural clusters, it is possible to study associative processes in vitro; a 3-neural model of associative long-term changes in synaptic efficiency has been developed. [ABSTRACT FROM AUTHOR]

Previously consolidated memories can become temporarily labile upon reactivation. Reactivation-based memory updating is chiefly studied in young subjects, so we aimed to assess this process across the lifespan. To do this, we developed a behavioural paradigm wherein a reactivated object memory is updated with contextual information; 3-month-old and 6-month-old male C57BL/6 mice displayed object memory updating, but 12-month-old mice did not. We found that M1 muscarinic acetylcholine receptor signaling during reactivation was necessary for object memory updating in the young mice. Next, we targeted this mechanism in an attempt to facilitate object memory updating in aging mice. Remarkably, systemic pharmacological M1 receptor activation reversed the age-related deficit. Quantification of cholinergic system markers within perirhinal cortex revealed subtle cellular changes that may contribute to differential performance across age groups. These findings suggest that natural cholinergic change across the lifespan contributes to inflexible memory in the aging brain. • Memory reactivation can signal an opportunity to update previously stored memory. • Muscarinic receptor activity gates post-reactivation object memory updating in mice. • Healthy and moderately aged mice display an object memory updating impairment. • An M1 muscarinic receptor agonist can reverse age-related memory updating deficits. [ABSTRACT FROM AUTHOR]

The post-retrieval extinction paradigm, rooted in reconsolidation theory, holds promise for enhancing extinction learning and addressing anxiety and trauma-related disorders. This study investigates the impact of two reminder types, mild US-reminder (US-R) and CS-reminder (CS-R), along with a no-reminder extinction, on fear recovery prevention in a categorical fear conditioning paradigm. Scalp EEG recordings during reminder and extinction processes were conducted in a three-day design. Results show that the US-R group exhibits a distinctive extinction learning pattern, characterized by a slowed-down yet successful process and pronounced theta-alpha desynchronization (source-located in the prefrontal cortex) during CS processing, followed by enhanced synchronization (source-located in the anterior cingulate) after shock cancellation in extinction trials. These neural dynamics correlate with the subtle advantage of US-R in the Day 3 recovery test, presenting faster spontaneous recovery fading and generally lower fear reinstatement responses. Conversely, the CS reminder elicits CS-specific effects in later episodic tests. The unique neural features of the US-R group suggest a larger prediction error and subsequent effortful conflict learning processes, warranting further exploration. [ABSTRACT FROM AUTHOR]

Experimental findings showing that retrieved memories are labile and vulnerable to disruption have led to important theoretical ideas at a basic science level that have been applied to the clinic at a translational level. At a theoretical level, these findings suggest that retrieved memories can be modulated by behavioral or pharmacological treatments as they are reconsolidated and returned to storage. At a clinical level, these findings suggest that treatments that target reconsolidation may help dampen or even erase especially problematic memories, such as those associated with trauma. However, there are many caveats to these effects and issues that need to be considered when thinking broadly about retrieval-induced plasticity and extensions into the clinic. First, performance during a memory test often does not reflect the entirety of the animal's knowledge about a situation; asking questions in different ways may reveal the presence of a memory that was thought to be eliminated. Second, although reconsolidation and extinction are often treated as competing processes, there is abundant evidence that extinction can progress through associative and nonassociative changes in the original memory that are often described in terms of reconsolidation effects. Third, targeting a reconsolidation process as a therapeutic may not be helpful in disorders like posttraumatic stress disorder, in which traumatic experiences induce a cascade of symptoms that are self-perpetuating and may ultimately maintain themselves long after trauma. Underlying all of these challenges is the need for a rich theoretical framework focused on retrieval-induced plasticity that is informed by developments in associative learning theory. [ABSTRACT FROM AUTHOR]

Introduction: Reactivation of already consolidated memory can initiate its destabilization, making the memory trace labile. Normally, this destabilization is followed by reconsolidation of the memory trace, enriched by newly acquired experience. Disrupting the reconsolidation process, for example, by inhibiting protein synthesis, impairs subsequent memory retrieval, leading to reminderrelated amnesia. Previous studies in various species have shown that this impairment can be prevented by using NMDA receptor antagonists, which interfere with memory destabilization. Methods: In the present study we examined this phenomenon using a one-trial passive avoidance learning model in newborn chicks, the hypothesis being that inactivation of the NMDA-mediated transmission during memory reactivation would inhibit the memory trace labilization and thus prevent the reminderrelated amnesia. Results: We found that reminder-associated administration of the NMDA receptor antagonist MK-801 or one of the protein synthesis inhibitors (anisomycin, cycloheximide, 2-deoxygalactose) each alone produced amnesia. However, when combined, injection of MK-801 before the reminder prevented amnesia induced by protein synthesis inhibitors. Discussion: We suggest that the observed paradoxical effect implicates the involvement of NMDA receptors in both protein synthesis-independent engram destabilization upon its retrieval and protein synthesismediated engram stabilization after its updating. This puzzling dual role of NMDA receptors in memory destabilization/restabilization requires further investigation. [ABSTRACT FROM AUTHOR]

The retrieval–extinction paradigm based on memory reconsolidation can prevent fear memory recurrence more effectively than the extinction paradigm. High-intensity fear memories tend to resist reconsolidation. Novelty–retrieval–extinction can promote the reconsolidation of fear memory lacking neuroplasticity in rodents; however, whether it could effectively promote high-intensity fear memory reconsolidation in humans remains unclear. Using 120 human participants, we implemented the use of the environment (novel vs. familiar) with the help of virtual reality technology. Novelty environment exploration was combined with retrieval–extinction in fear memory of two intensity levels (normal vs. high) to examine whether novelty facilitates the reconsolidation of high-intensity fear memory and prevents recurrence. Skin conductance responses were used to clarify novelty–retrieval–extinction effects at the behavioral level across three experiments. Retrieval–extinction could prevent the reinstatement of normal-intensity fear memory; however, for high-intensity fear memory, only the novelty–retrieval–extinction could prevent recurrence; we further validated that novelty–retrieval–extinction may be effective only when the environment is novel. Although the high-intensity fear memory is higher than normal-intensity in this study, it may be insufficient relative to fear experienced in real-world contexts or by individuals with mental disorders. To some extent, these findings indicate that the novelty–retrieval–extinction paradigm could prevent the recurrence of high-intensity fear memory, and we infer that novelty of environment may play an important role in novelty–retrieval–extinction paradigm. The results of this study have positive implications for the existing retrieval extinction paradigm and the clinical treatment of phobia. • Retrieval-extinction could prevent reinstatement of normal-intensity fear. • Novelty-retrieval-extinction could prevent recurrence of high-intensity fear. • Novelty of environment may play an important role in novelty–retrieval–extinction paradigm. [ABSTRACT FROM AUTHOR]

Here, we describe the efforts we dedicated to the challenge of modifying entrenched emotionally laden memories. In recent years, through a number of collaborations and using a combination of behavioral, molecular, and computational approaches, we: (a) developed novel approaches to fear attenuation that engage mechanisms that differ from those engaged during extinction (Monfils), (b) examined whether our approaches can generalize to other reinforcers (Lee, Gonzales, Chaudhri, Cofresi, and Monfils), (c) derived principled explanations for the differential outcomes of our approaches (Niv, Gershman, Song, and Monfils), (d) developed better assessment metrics to evaluate outcome success (Shumake and Monfils), (e) identified biomarkers that can explain significant variance in our outcomes of interest (Shumake and Monfils), and (f) developed better basic research assays and translated efforts to the clinic (Smits, Telch, Otto, Shumake, and Monfils). We briefly highlight each of these milestones and conclude with final remarks and extracted principles. [ABSTRACT FROM AUTHOR]

Existing simplified procedures for evaluating soil liquefaction potential or for estimating excess pore pressures during earthquakes are typically based on undrained cyclic tests performed on saturated soil samples under controlled loading and boundary conditions. Under such conditions, the effect of excess pore pressure (ue) dissipation and redistribution to neighboring soil layers cannot be accounted for. Existing simplified procedures treat liquefiable layers as isolated soil layers without any boundary conditions even if dense and loose layers are very thin, permeable, and adjacent to each other. However, redistribution is likely to increase and decrease ue in the neighboring dense and loose layers respectively. Until now, no procedure short of fully coupled numerical analysis is available to estimate the importance of redistribution. This paper presents an approximate analytical procedure for assessing the effects of ue redistribution in (1) soil layers that would have liquefied if they were undrained, and (2) soil layers that would have not liquefied even if undrained. It is found that a layer that is initially assumed liquefied under undrained conditions might not even liquefy accounting for the ue redistribution to neighboring layers. On the other hand, a layer initially assumed to not liquefy can develop significant ue and can even liquefy due to pore pressure migration from the neighboring layers. Thus, accounting for redistributed ue is important for liquefaction consequence assessment quantification, particularly in systems that span the depth of these effects like deep foundations. Migration of u toward the tip of a pile can reduce its capacity, even if the tip is embedded in a dense sand layer. On the other hand, if redistribution can result in the reduction of ue in initially assumed liquefied layers, risks associated with liquefaction might be avoided. A criterion is also developed to evaluate the thicknesses of a layer below which redistribution could prevent liquefaction even if the layer is deemed liquefied according to the existing liquefaction-triggering procedures. Finally, the proposed procedure is illustrated by application to selected shaking events of centrifuge tests involving liquefaction of layered soil profiles. The predictions from the procedure matched the centrifuge test results reasonably. [ABSTRACT FROM AUTHOR]

Drug-associated pathological memory remains a critical factor contributing to the persistence of substance use disorder. Pharmacological amnestic manipulation to interfere with drug memory reconsolidation has shown promise for the prevention of relapse. In a rat heroin self-administration model, we examined the impact of rimonabant, a selective cannabinoid receptor indirect agonist, on the reconsolidation process of heroin-associated memory. The study showed that immediately administering rimonabant after conditioned stimuli (CS) exposure reduced the cue- and herion + cue-induced heroin-seeking behavior. The inhibitory effects lasted for a minimum of 28 days. The effect of Rimonabant on reduced drug-seeking was not shown when treated without CS exposure or 6 hours after CS exposure. These results demonstrate a disruptive role of rimonabant on the reconsolidation of heroin-associated memory and the therapeutic potential in relapse control concerning substance use disorder. [ABSTRACT FROM AUTHOR]

Introduction: Reactivation of already consolidated memory can initiate its destabilization, making the memory trace labile. Normally, this destabilization is followed by reconsolidation of the memory trace, enriched by newly acquired experience. Disrupting the reconsolidation process, for example, by inhibiting protein synthesis, impairs subsequent memory retrieval, leading to reminder-related amnesia. Previous studies in various species have shown that this impairment can be prevented by using NMDA receptor antagonists, which interfere with memory destabilization.Methods: In the present study we examined this phenomenon using a one-trial passive avoidance learning model in newborn chicks, the hypothesis being that inactivation of the NMDA-mediated transmission during memory reactivation would inhibit the memory trace labilization and thus prevent the reminder-related amnesia.Results: We found that reminder-associated administration of the NMDA receptor antagonist MK-801 or one of the protein synthesis inhibitors (anisomycin, cycloheximide, 2-deoxygalactose) each alone produced amnesia. However, when combined, injection of MK-801 before the reminder prevented amnesia induced by protein synthesis inhibitors.Discussion: We suggest that the observed paradoxical effect implicates the involvement of NMDA receptors in both protein synthesis-independent engram destabilization upon its retrieval and protein synthesismediated engram stabilization after its updating. This puzzling dual role of NMDA receptors in memory destabilization/restabilization requires further investigation.

Rationale: The mammalian target of rapamycin (mTOR) kinase is known to mediate consolidation and reconsolidation of aversive memories. Most studies in this area use a forward conditioning paradigm in which the conditioned stimulus (CS) precedes the unconditioned stimulus (US). Little is known, however, about the neurobiological underpinnings of backwards (BW) conditioning paradigms, particularly in female mice. In BW conditioning, the CS does not become directly associated with the US; it instead evokes conditioned fear by reactivating a memory of the conditioning context and indirectly retrieving a memory of the aversive US. Objectives: We sought to examine BW conditioned fear memory processes in female mice. First, we examined whether freezing to a BW CS is mediated by fear to the conditioning context. Second, we tested whether blocking consolidation of a BW CS attenuated memory of the CS and conditioning context. Finally, we tested whether blocking reconsolidation of a BW CS attenuated memory of the conditioning context. Results: We show that conditioned freezing to a BW CS is mediated by fear to the conditioning context. Furthermore, rapamycin—an mTOR inhibitor, when given immediately following BW conditioning, impairs consolidation of both cued and contextual fear memory. Similarly, rapamycin given following retrieval of a BW CS blocks context recall. Rapamycin is acting on reconsolidation as CS retrieval is necessary to see the effects of rapamycin on context memory recall. Conclusions: Our study provides novel evidence that indirect retrieval cues are sensitive to rapamycin in female mice. The capacity to indirectly reactivate memories and render them susceptible to disruption is critical in the translation of reconsolidation-based approaches to the clinic. [ABSTRACT FROM AUTHOR]

Sometimes referred to as a memory reconsolidation treatment, Muss Rewind Therapy (MRT) is a brief psychological intervention which has shown promise in treating symptoms related to some forms of traumatic experience. This study aimed at adding to minimal existing research by exploring the experiences of UK participants who have chosen to self‐refer for MRT for help with symptoms they attributed to some form of previous traumatic experience. Ten participants were interviewed online, and qualitative data were collected using video recordings and transcription. A semistructured framework was employed to explore participants' individual experiences of MRT. All participants rated MRT as helping alleviate the symptoms they related to a previous traumatic experience. Several key themes emerged regarding the participants' experiences of the treatment, including the overall role of the therapist; participants being at the end of their tether before seeking help; experiencing negative emotions during the intervention; repetition of the MRT process in the therapy room; and experiencing some positive outcomes. However, it was unclear whether positive impacts reported after MRT were due specifically to MRT or nonspecific therapy factors because of variations in the way the MRT protocol was delivered and inclusion of other techniques in or before the MRT sessions. Whilst more rigorous research is needed, including research which follows a strict protocol when MRT is provided, to compare MRT versus control group, this novel addition to the existing research, which looks at clients' perspectives on their experiences and their perceived effectiveness of MRT, can add to and inform further research development. [ABSTRACT FROM AUTHOR]

This review examines cognitive and neural mechanisms underlying social influence on autobiographical memory. We aim for this review to serve as a bridge between researchers who focus on veridicality (e.g., eyewitness memory) and those who give primacy to meaning, especially given the elusive nature of measuring veridicality in uncontrolled personal experiences. We assess whether mechanisms are similar for three aspects of memories, namely facts, interpretations, and autobiographical reasoning. We present a model of memory change in facts and interpretations that is incidental and time-bound, in contrast to change in autobiographical reasoning that is more deliberate and open to influence. We emphasize the empirical challenges of studying memory that is truly autobiographical alongside the compromise to experimental control required to answer certain questions. We finally argue that autobiographical memory represents a naturalistic domain where memory processes, reasoning processes, and conversational influences collide, with potential implications for applied research on veridicality. General Audience Summary: Memory researchers have long understood that memories can be influenced by various social factors, including things said in conversations with others. The most prominent findings relate to eyewitness memory, when people include details from conversations after an event occurs that were not in their initial memory. In order to conduct these studies, researchers often achieve experimental control by showing all participants the same event, through videos or simulations, and take charge to introduce the false information themselves. This paradigm has been powerful in showing how memory can change, but we ask whether the findings from these studies can be applied to the strong emotions and confused conversations that often accompany highly salient personal experiences. We especially note that people often talk with others after important experiences, and so when researchers study personal experiences, or autobiographical memories, we lose the same experimental control of other studies. Our review may be especially relevant to considering eyewitnesses speaking with each other after an event, parents discussing events with their children, and cognitive interview techniques. In this review, we consider whether the cognitive and neural mechanisms used to understand social influences on memory can be applied to research on autobiographical memory. We divide autobiographical memories into three categories, facts, interpretations, and autobiographical reasoning, and review research on all three, considering how they are similar, different, and how they influence each other. While we conclude that many aspects of controlled memory studies can be applied to autobiographical memory, we argue that much more can still be learned from nonexperimental approaches that study memory in more naturalistic contexts, especially with regard to how these different components of autobiographical memory influence each other. [ABSTRACT FROM AUTHOR]

Fear memory formation and retention rely on the activation of distributed neural circuits. The basolateral amygdala (BLA) and ventral hippocampus (VH) in particular are two regions that support contextual fear memory processes and share reciprocal connections. The VH → BLA pathway is critical for increases in fear after initial learning, in both fear renewal following extinction learning and during fear generalization. This raises the possibility that functional changes in VH projections to the BLA support increases in learned fear. In line with this, fear can also be increased with alterations to the original content of the memory via reconsolidation, as in fear elevation procedures. However, very little is known about the functional changes in the VH → BLA pathway supporting reconsolidation-related increases in fear. In this study, we used in vivo extracellular electrophysiology to examine the functional neuronal changes within the BLA and in the VH → BLA pathway as a result of fear elevation and standard fear retrieval procedures. Elevated fear expression was accompanied by higher BLA spontaneous firing compared to a standard fear retrieval condition. Across a range of stimulation frequencies, we also found that VH stimulation evoked higher BLA firing following fear elevation compared to standard retrieval. These results suggest that fear elevation is associated with an increased capacity of the VH to drive neuronal activity in the BLA, highlighting a potential circuit involved in strengthening existing fear memories. [ABSTRACT FROM AUTHOR]

Long-term memories are not stored in a stable state but must be flexible and dynamic to maintain relevance in response to new information. Existing memories are thought to be updated through the process of reconsolidation, in which memory retrieval initiates destabilization and updating to incorporate new information. Memory updating is impaired in old age, yet little is known about the mechanisms that go awry. One potential mechanism is the repressive histone deacetylase 3 (HDAC3), which is a powerful negative regulator of memory formation that contributes to age-related impairments in memory formation. Here, we tested whether HDAC3 also contributes to age-related impairments in memory updating using the Objects in Updated Locations (OUL) paradigm. We show that blocking HDAC3 immediately after updating with the pharmacological inhibitor RGFP966 ameliorated age-related impairments in memory updating in 18-m.o. male mice. Surprisingly, we found that post-update HDAC3 inhibition in young (3-m.o.) male mice had no effect on memory updating but instead impaired memory for the original information, suggesting that the original and updated information may compete for expression at test and HDAC3 helps regulate which information is expressed. To test this idea, we next assessed whether HDAC3 inhibition would improve memory updating in young male mice given a weak, subthreshold update. Consistent with our hypothesis, we found that HDAC3 blockade strengthened the subthreshold update without impairing memory for the original information, enabling balanced expression of the original and updated information. Together, this research suggests that HDAC3 may contribute to age-related impairments in memory updating and may regulate the strength of a memory update in young mice, shifting the balance between the original and updated information at test.

Introduction. To study the regularities of formation of individual experience we summarize the results of research in consolidation, reconsolidation of memory, extinction and forgetting within a unified idea that considers them in the frames of systems psychophysiology as manifestations of two coordinated processes: formation of new experience and modification of previously formed experience. Theoretical Justification. Within the framework of the theory of functional systems, it had been proposed that systemogenesis also takes place in adults, since the formation of a new behavioral act is the formation of a new system. In studies with single-neuron activity recording it was shown that during performance of new behavior the simultaneous activation of multiple earlier formed systems occurs along with activation of new systems formed during learning. Therefore, we consider consolidation, reconsolidation, extinction, and forgetting as manifestations of reorganization of individual experience as a whole. The results of research in the neurophysiology of memory show that the processes of memory formation (including its consolidation) and forgetting are not mutually exclusive and can take place independently. Some forms of forgetting are caused by the inability to use memory, rather than by its removal, that makes forgetting similar to the formation of extinction. Discussion. We argue that (re)consolidation, extinction and forgetting may be based on similar long-term changes in previously formed experience, in particular those that do not let some elements of this experience to be utilized further.

Abstract Background Memory impairment caused by Toxoplasma gondii infection has been documented. Berberine (BRB) is well known for its enhancing effects on memory and has shown promising results. However, the impact of BRB on T. gondii infection and schizophrenia-induced consolidation and reconsolidation memory impairment is still unclear. Here; we examined the effect of BRB on the inhibitory avoidance (IA) memory consolidation and reconsolidation impairment induced by T. gondii infection, and ketamine (Ket) as a pharmacological model of schizophrenia. Also; the brain-derived neurotrophic factor (BDNF) levels in the medial prefrontal cortex (mPFC) and hippocampus were analyzed. Methods Rats were infected with T. gondii RH strain or received Ket (30 mg/kg/day) intraperitoneally (i.p) for at least five consecutive days (as the model of schizophrenia). Then followed by oral administration with BRB (25 mg/kg/day) for five days. Finally, the IA memory retention test was examined 48 post-conditioning, and BDNF was measured. Results Results indicated IA memory impairment in T. gondii-infected animals since lower step-through latency (STL) was observed than in control animals. We found significant (P = 0.01, P = 0.001) elevations in STL and a significant decrease (P = 0.001) in total time spent in the dark area following BRB administration in infected and Ket-treated rats, indicating improvement (increased STL) in consolidation and reconsolidation memory. Moreover, BDNF levels were reduced (P = 0.01) in the hippocampus and mPFC regions of both T. gondii- infected and Ket-induced groups, which remarkably enhanced after BRB treatment. Furthermore; we found that BRB administration notably increased the mPFC BDNF levels in mPFC (P

Fear memory formation and retention rely on the activation of distributed neural circuits. The basolateral amygdala (BLA) and ventral hippocampus (VH) in particular are two regions that support contextual fear memory processes and share reciprocal connections. The VH → BLA pathway is critical for increases in fear after initial learning, in both fear renewal following extinction learning and during fear generalization. This raises the possibility that functional changes in VH projections to the BLA support increases in learned fear. In line with this, fear can also be increased with alterations to the original content of the memory via reconsolidation, as in fear elevation procedures. However, very little is known about the functional changes in the VH → BLA pathway supporting reconsolidation-related increases in fear. In this study, we used in vivo extracellular electrophysiology to examine the functional neuronal changes within the BLA and in the VH → BLA pathway as a result of fear elevation and standard fear retrieval procedures. Elevated fear expression was accompanied by higher BLA spontaneous firing compared to a standard fear retrieval condition. Across a range of stimulation frequencies, we also found that VH stimulation evoked higher BLA firing following fear elevation compared to standard retrieval. These results suggest that fear elevation is associated with an increased capacity of the VH to drive neuronal activity in the BLA, highlighting a potential circuit involved in strengthening existing fear memories.

Practicing motor skills stabilizes and strengthens motor memories by repeatedly reactivating and reconsolidating them. The conventional view, by which a repetitive practice is required for substantially improving skill performance, has been recently challenged by behavioral experiments, in which even brief reactivations of the motor memory have led to significant improvements in skill performance. However, the mechanisms which facilitate brief reactivation-induced skill improvements remain elusive. While initial memory consolidation has been repeatedly associated with increased neural excitation and disinhibition, reconsolidation has been shown to involve a poorly understood mixture of both excitatory and inhibitory alterations. Here, we followed a 3-d reactivation-reconsolidation framework to examine whether the excitatory/inhibitory mechanisms which underlie brief reactivation and repetitive practice differ. Healthy volunteers practiced a motor sequence learning task using either brief reactivation or repetitive practice and were assessed using ultrahigh field (7T) magnetic resonance spectroscopy at the primary motor cortex (M1). We found that increased inhibition (GABA concentrations) and decreased excitation/inhibition (glutamate/GABA ratios) immediately following the brief reactivation were associated with overnight offline performance gains. These gains were on par with those exhibited following repetitive practice, where no correlations with inhibitory or excitatory changes were observed. Our findings suggest that brief reactivation and repetitive practice depend on fundamentally different neural mechanisms and that early inhibition--and not excitation--is particularly important in supporting the learning gains exhibited by brief reactivation. [ABSTRACT FROM AUTHOR]

Introduction: Despite the positive outcomes observed in numerous individuals undergoing trauma-focused psychotherapy for PTSD, veterans with this condition experience notably diminished advantages from such therapeutic interventions in comparison to non-military populations. Methods: In a preliminary study we investigated the efficacy of an innovative treatment approach in a small sample of veterans (n = 7). Recognizing that accessing and targeting trauma memory in veterans with PTSD may be more challenging compared to other patient populations, we employed unique and personalized retrieval cues that engaged multiple senses and were connected to the context of their trauma. This was followed by a session focused on memory reconsolidation, which incorporated both psychological techniques (i.e., imagery rescripting) and a pharmacological component (i.e., 40 mg of propranolol). Results: The findings from this small-scale case series cautiously indicate that this brief intervention, typically consisting of only one or two treatment sessions, shows promise in producing significant effects on symptoms of PTSD, distress and quality of life.This is particularly noteworthy given the complex symptomatology experienced by the veterans in this study. Conclusion: To summarize, there are grounds for optimism regarding this brief treatment of combat-related PTSD. It appears that the potential for positive outcomes is far greater than commonly believed, as demonstrated by the encouraging results of this pilot study. [ABSTRACT FROM AUTHOR]

The current study tested the effects of attentive versus distracted listening on both speakers and listeners in recall of an autobiographical memory. Participants included 128 pairs of friends who spoke with each other over a video call about recent negative experience that one of them had. Participants were randomly assigned to be speakers or listeners, and listeners were randomly assigned to an attentive and a distracted condition. Memory narratives were coded for factual and interpretive content. Participants returned approximately 4 weeks later, when both speaker and listener separately reported their memories of the prior conversation. Attentive listening was linked both to greater recall by the speaker at time 1 and greater listener recall at time 2, but not to speaker's recall at time 2. Results show the effects of listener contributions to recall in the moment but raise questions as to whether they persist beyond the conversation in many scenarios. [ABSTRACT FROM AUTHOR]

The susceptibility to drug cravings evoked by stimuli poses a formidable hurdle in the treatment of addiction and the prevention of relapse. Pharmacological interventions targeting drug‐associated memories hold promise for curbing relapse by impeding the process of memory reconsolidation, predominantly governed by cAMP signalling. Exchange Protein Activated by cAMP (Epac) serves as a distinctive mediator of cAMP signalling, which has been implicated in reinforcing the effects of cocaine and facilitating the acquisition. Nonetheless, the role of Epac in heroin‐related memory and the subsequent seeking behaviour remains enigmatic. In this study, we explored the impact of Epac activation on the reconsolidation process of drug‐related memories associated with heroin self‐administration. Over the course of 10 consecutive days, rats underwent training, wherein they acquired the behaviour of nose poking to obtain heroin accompanied by a tone + light cue. This nose‐poking behaviour was subsequently extinguished when heroin infusion and cue presentation were discontinued. Subsequently, we administered 8‐pCPT‐cAMP (8‐CPT), an Epac‐specific activator, into the basolateral amygdala at various time points, either in the presence or absence of a conditioned stimulus. Our findings demonstrate that administering 8‐CPT immediately after memory retrieval effectively reduces cue‐ and heroin‐induced reinstatement, with the observed effects persisting significantly for a minimum of 28 days. However, infusion of 8‐CPT for a duration of 6 h following the memory retrieval trial, or without it altogether, had no discernible impact. Thus, these findings strongly suggest that Epac activation can disrupt the reconsolidation of heroin‐associated memory, thereby diminishing the reinstatement of heroin‐seeking behaviour. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Behavioral Neuroscience. It discusses the destabilization of maladaptive memory and provides updates and future perspectives on this topic. The editorial highlights the importance of understanding the molecular and physiological signatures of memory destabilization and the potential for therapies based on the modulation of this process. It also presents original research articles that explore the boundary conditions and mechanisms underlying memory destabilization, with a focus on fear and anxiety disorders and drug addiction. The editorial concludes by emphasizing the contributions of this research to the theoretical framework and future studies on the modulation of maladaptive memories. [Extracted from the article]

This study investigates whether spermidine (SPD), an endogenous polyamine, alters extinction and reinstatement of alcohol-induced conditioned place preference (CPP) in adult female Swiss mice. CPP was induced by injecting alcohol (1.8 g/kg, i.p.) and placing the animals in the drug-associated compartment for 10 min in four alternate days. During extinction, animals received vehicle or SPD (3, 10 or 30 mg/kg), and were placed in the drug-associated compartment for 10 min in 4 alternate days. Alcohol re-exposure was performed in the alcohol-paired compartment. In a second experiment, after conditioning, animals received vehicle, the N-methyl-d-aspartate (NMDA) receptor polyamine binding site antagonist arcaine (ARC, 0.1 mg/kg), SPD (10 mg/kg) or the association of both (ARC+SDP) in the drug-associated compartment. Animals were then sequentially subjected to alcohol re-exposure and a post-reexposure test. Spermidine did not alter CPP extinction, but prevented the reinstatement of CPP induced by alcohol reexposure. Arcaine prevented the effect of spermidine on alcohol-induced CPP reinstatement. The results suggest that SPD may facilitate the reconsolidation of conditioning memory, disrupting CPP. This effect seems to involve the polyamine binding site at the NMDA receptor, because it is prevented by ARC.

IntroductionDespite the positive outcomes observed in numerous individuals undergoing trauma-focused psychotherapy for PTSD, veterans with this condition experience notably diminished advantages from such therapeutic interventions in comparison to non-military populations.MethodsIn a preliminary study we investigated the efficacy of an innovative treatment approach in a small sample of veterans (n = 7). Recognizing that accessing and targeting trauma memory in veterans with PTSD may be more challenging compared to other patient populations, we employed unique and personalized retrieval cues that engaged multiple senses and were connected to the context of their trauma. This was followed by a session focused on memory reconsolidation, which incorporated both psychological techniques (i.e., imagery rescripting) and a pharmacological component (i.e., 40 mg of propranolol).ResultsThe findings from this small-scale case series cautiously indicate that this brief intervention, typically consisting of only one or two treatment sessions, shows promise in producing significant effects on symptoms of PTSD, distress and quality of life.This is particularly noteworthy given the complex symptomatology experienced by the veterans in this study.ConclusionTo summarize, there are grounds for optimism regarding this brief treatment of combat-related PTSD. It appears that the potential for positive outcomes is far greater than commonly believed, as demonstrated by the encouraging results of this pilot study.

Memory consolidation is the process underlying the stabilization of labile short-term memory and the generation of long-term memory for persistent memory storage. The retrieval of contextual fear memory induces two distinct and opposite memory processes: reconsolidation and extinction. Reconsolidation re-stabilizes retrieved memory for re-storage, whereas memory extinction weakens fear memory and generates a new inhibitory memory. Importantly, the requirement for new gene expression is a critical biochemical feature of the consolidation, reconsolidation, and long-term extinction of memory. The locus coeruleus (LC) is a small nucleus in the brain stem that is composed predominantly of noradrenergic neurons that project to many brain regions. Recent studies have shown that the LC plays modulatory roles in the consolidation and extinction of auditory fear memory through its projections to brain regions contributing to memory storage. Here, we show that the LC is required for the consolidation, reconsolidation, and long-term extinction of contextual fear memory. We first observed that c-fos expression was induced in the LC following contextual fear conditioning to induce consolidation and following short and long re-exposure to the conditioning context to induce reconsolidation and long-term extinction, respectively. More importantly, inhibition of protein synthesis in the LC by a micro-infusion of anisomycin blocked the consolidation, reconsolidation, and long-term extinction of contextual fear memory. Our findings suggest that consolidation, reconsolidation, and long-term extinction occur in the LC and that the LC plays an essential role in memory storage and maintenance.

This work aims to study the epigenetic mechanisms of regulating long-term context memory in the gastropod mollusk: Helix. We have shown that RG108, an inhibitor of DNA methyltransferase (DNMT), impaired long-term context memory in snails, and this impairment can be reversed within a limited time window: no more than 48 h. Research on the mechanisms through which the long-term context memory impaired by DNMT inhibition could be reinstated demonstrated that this effect depends on several biochemical mechanisms: nitric oxide synthesis, protein synthesis, and activity of the serotonergic system. Memory recovery did not occur if at least one of these mechanisms was impaired. The need for the joint synergic activity of several biochemical systems for a successful memory rescue confirms the assumption that the memory recovery process depends on the process of active reconsolidation, and is not simply a passive weakening of the effect of RG108 over time. Finally, we showed that the reactivation of the impaired memory by RG108, followed by administration of histone deacetylase inhibitor sodium butyrate, led to memory recovery only within a narrow time window: no more than 48 h after memory disruption. [ABSTRACT FROM AUTHOR]

• Detection of prediction error is a determining condition for reactivating the recent motor memory. • The level of task variability influences the strengthening of recent motor memory. • The level of prediction error generated influences the reconsolidation process. This study investigated strategies based on the reconsolidation process to promote the strengthening effect of human motor memory. The aim of this study was to evaluate the influence of reactivating the memory of a newly acquired motor skill and performing interventions during its reconsolidation process on motor performance. Sixty healthy participants learned a new Sequential Visual Isometric Pinch Task – SVIPT during the first experimental session. In the second experimental session that was held on the same day, 6 h after session 1, the participants were divided into six different groups. In session 2, there were distinctions between the experimental groups concerning two issues: the presence or absence of a formal memory reactivation session characterized by the execution of repetitions of the learned motor task and the execution of different types of interventions after reactivation (training with the original, slightly modified, or moderately modified motor task). All groups performed the third session to retest the learned motor skill, 24 h after session 1. The results showed that using training with moderate task variability during memory reconsolidation provides greater motor skill performance gain when compared to repetitive training of the same learned task. Furthermore, performing a session exclusively dedicated to reactivation with the practice of the originally learned task was not a determining condition for recent motor memory reactivation, but rather the induction of prediction error during the reactivation. [ABSTRACT FROM AUTHOR]

The classical fear conditioning is extensively used in preclinical studies as an animal model for post-traumatic stress disorder (PTSD). During the reconsolidation process, when memories are retrieved, the memory becomes susceptible to change and amenable to intervention. Interventions applied during the reconsolidation process triggered by exposure to a conditioned stimulus (CS) primarily lead to a decrease in fear responses triggered only by the exposed CS, without generalizing to other fear-related cues. However, in real-life scenarios, multiple CS's can be linked to fear-inducing events. Therefore, recent studies have focused on the reactivation procedure with an unconditioned stimulus (US), which is believed to result in the reconsolidation of the entire fear memory. Interventions applied during the reconsolidation process that are triggered by US-based retrieval are considered more effective. Grounding on the fear memory studies activated by either CS or US, this review study discussed how acquired fear can be extinguished through behavioral and pharmacological interventions. Additionally, the brain regions involved in fear memory and the impact of gender differences on fear memory were also addressed. The aim of this review was to contribute to the field by exploring more effective treatment approaches for fear disorders. [ABSTRACT FROM AUTHOR]

The persistence of maladaptive heroin‐associated memory, which is triggered by drug‐related stimuli that remind the individual of the drug's pleasurable and rewarding effects, can impede abstinence efforts. Cyclin‐dependent kinase 5 (Cdk5), a neuronal serine/threonine protein kinase that plays a role in multiple neuronal functions, has been demonstrated to be involved in drug addiction and learning and memory. Here, we aimed to investigate the role of cdk5 activity in the basolateral amygdala (BLA) in relapse to heroin seeking, using a self‐administration rat model. Male rats underwent 10 days of heroin self‐administration training, during which an active nose poke resulted in an intravenous infusion of heroin that was accompanied by a cue. The rats then underwent nose poke extinction for 10 days, followed by subsequent tests of heroin‐seeking behaviour. We found that intra‐BLA infusion of β‐butyrolactone (100 ng/side), a Cdk5 inhibitor, administered 5 min after reactivation, led to a subsequent decrease in heroin‐seeking behaviour. Further experiments demonstrated that the effects of β‐butyrolactone are dependent on reactivated memories, temporal‐specific and long‐lasting on relapse of heroin‐associated memory. Results provide suggestive evidence that the activity of Cdk5 in BLA is critical for heroin‐associated memory and that the specific inhibitor, β‐butyrolactone, may hold potential as a substance for the treatment of heroin abuse. [ABSTRACT FROM AUTHOR]

Newly acquired memory traces have been thought to become stable and resistant to interruption after they are stored in long-term memory. However, according to a recent research drugs such as betaadrenergic receptor antagonists enable memories to be updated and rewritten when administered during consolidation and reconsolidation. Propranolol is a widely used beta-adrenergic receptor antagonist that disrupts the consolidation and reconsolidation processes of memory formation as it inhibits protein synthesis in the central nervous system. This review aims to discuss the memory impairing effect of the systemic and intracerebral administration of propranolol during the consolidation and reconsolidation processes associated with different learning tasks. In doing so, this review will help elucidate the effects of propranolol on different stages of memory formation. Since learning and maladaptive memories underpin some of the most common psychological disorders, such as phobias, post-traumatic stress disorder, addiction, drugseeking behavior, and so on, a thorough understanding of propranolol's memory-impairing effect has significant clinical value and the potential to help people suffering from these disorders. [ABSTRACT FROM AUTHOR]

Background: Memory impairment caused by Toxoplasma gondii infection has been documented. Berberine (BRB) is well known for its enhancing effects on memory and has shown promising results. However, the impact of BRB on T. gondii infection and schizophrenia-induced consolidation and reconsolidation memory impairment is still unclear. Here; we examined the effect of BRB on the inhibitory avoidance (IA) memory consolidation and reconsolidation impairment induced by T. gondii infection, and ketamine (Ket) as a pharmacological model of schizophrenia. Also; the brain-derived neurotrophic factor (BDNF) levels in the medial prefrontal cortex (mPFC) and hippocampus were analyzed. Methods: Rats were infected with T. gondii RH strain or received Ket (30 mg/kg/day) intraperitoneally (i.p) for at least five consecutive days (as the model of schizophrenia). Then followed by oral administration with BRB (25 mg/kg/day) for five days. Finally, the IA memory retention test was examined 48 post-conditioning, and BDNF was measured. Results: Results indicated IA memory impairment in T. gondii-infected animals since lower step-through latency (STL) was observed than in control animals. We found significant (P = 0.01, P = 0.001) elevations in STL and a significant decrease (P = 0.001) in total time spent in the dark area following BRB administration in infected and Ket-treated rats, indicating improvement (increased STL) in consolidation and reconsolidation memory. Moreover, BDNF levels were reduced (P = 0.01) in the hippocampus and mPFC regions of both T. gondii- infected and Ket-induced groups, which remarkably enhanced after BRB treatment. Furthermore; we found that BRB administration notably increased the mPFC BDNF levels in mPFC (P < 0.01) and hippocampus (P = 0.001) in the Ket-treated and rats infected with T. gondii. Conclusion: Taken together; BRB may be a valuable preclinical treatment for improving memory impairment through BDNF expression in PFC and hippocampus, therefore; BRB is suggested for memory disturbances induced by T. gondii infection. [ABSTRACT FROM AUTHOR]

Memory acquisition, formation and maintenance depend on synaptic posttranslational machinery and regulation of gene expression triggered by several transduction pathways. In turns, these processes lead to stabilization of synaptic modifications in neurons in the activated circuits. In order to study the molecular mechanisms involved in acquisition and memory, we have taken advantage of the context-signal associative learning and, more recently, the place preference task, of the crab Neohelice granulata. In this model organism, we studied several molecular processes, including activation of extracellular signal-regulated kinase (ERK) and the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) transcription factor, involvement of synaptic proteins such as NMDA receptors and neuroepigenetic regulation of gene expression. All these studies allowed description of key plasticity mechanisms involved in memory, including consolidation, reconsolidation and extinction. This article is aimed at review the most salient findings obtained over decades of research in this memory model. [ABSTRACT FROM AUTHOR]

The context in which sudden fearful events occur can be poorly encoded into memory. Yet, the consequences of the resulting context-impoverished memories remain unknown. We demonstrate that restricting the time available for context encoding during contextual fear conditioning causes maladaptively overgeneralized and inextinguishable fear. However, post-conditioning context exposure enables further context encoding through hippocampal reconsolidation-dependent memory updating. Updating in the conditioning context alleviates overgeneralization and restores capacity for extinction. However, updating in a similar safe context erroneously shifts fear from the dangerous to the safe context. We argue that these phenomena can be explained by uncertainty about where events occurred. Moreover, we show that a hippocampal-neocortical neurocomputational model based on this assumption successfully simulates and explains our observations. These findings reveal that context-impoverished memories are maladaptive and can be improved or distorted after recall, with implications for basic memory theory, memory distortion, and treatment of disorders like post-traumatic stress disorder.

When previously consolidated hippocampally dependent memory traces are reactivated they enter a vulnerable state in which they can be altered with new information, after which they must be re-consolidated in order to restabilize the trace. The existing body of literature on episodic reconsolidation largely focuses on the when and how of successful memory reactivation. What remains poorly understood is how the nature of newly presented information affects the likelihood of a vulnerable episodic memory being altered. We used our episodic memory reconsolidation paradigm to investigate if the intention to encode impacts what subsequently becomes attributed to an older, reactivated memory. Participants learned two lists of objects separated by 48 h. We integrated a modified item-list directed-forgetting paradigm into the encoding of the second object list by cueing participants to learn some of the objects intentionally (intentional learning), while other objects were presented without a cue (incidental learning). Under conditions of memory reactivation, subjects showed equal rates of memory modification for intentionally- and incidentally-learned objects. However, in the absence of reactivation we observed high misattribution rates of incidentally-learned objects. We consider two interpretations of these data, with contrasting implications for understanding the conditions that influence memory malleability, and suggest further work that should help decide between them.

Sleep and memory are complex phenomena that are not fully understood, and the underlying mechanisms are still not fully understood. Besides being an adaptive behavior, sleep can modulate plasticity in the brain at the level of synaptic connections between neurons and neuronal plasticity affects sleep. Understanding how sleep is modulated by internal and external stimuli and how sleep modulates memory and plasticity is a key question in neuroscience. Sleep is characterized as a brain state that optimizes the memory consolidation. Although the initial encoding of a memory is a fast process, its long-term maintenance requires processes that continue to replace relevant data for hours or even years. The general name of this process is memory consolidation and the replacement of existing memories is the reconsolidation process. Memory consolidation refers to a process in which unstable newly formed memory traces are progressively transformed into long-term memories and become more resistant to interaction, although they may remain susceptible to further updates and modifications. Consolidation results from the reactivation of recently encoded neuronal memory representations that occur during slow-wave activity and transform the relevant representations into long-term memory for integration. Continued rapid eye movement sleep can stabilize transformed memories. According to recent research, sleep-related consolidation processes can be placed in different sizes for different types of memory. Slow wave activity, which is restorative sleep, is hypothesized to play an important role in memory by processing and consolidating newly acquired information. In this review, general research was conducted on the relationship between sleep and memory.

The purpose of this work is to evaluate the reconsolidation of a carbon fiber composite with poly (aryl ether ketone) (PAEK)/carbon fiber laminates after suffering impacts from different energy levels (5, 10 and 30 J) and being restored by reconsolidation. For this comparison, thermal analysis, and compression after impact tests were performed to evaluate the properties of the material before and after the reconsolidation process. According to the found results, it was observed that with small damages it is possible to fully recover the material after new consolidation and for larger damages there is also a partial recovery compared to the base laminate. The material remains thermally stable in all situations, in other words, its thermal properties remain even after impact tests and reconsolidation process. [ABSTRACT FROM AUTHOR]

Associative learning and memory are fundamental behavioral processes through which organisms adapt to complex environments. Associative memory involves long‐lasting changes in synaptic plasticity. Dendritic spines are tiny protrusions from the dendritic shaft of principal neurons, providing the structural basis for synaptic plasticity and brain networks in response to external stimuli. Mounting evidence indicates that dendritic spine dynamics are crucial in different associative memory phases, including acquisition, consolidation, and reconsolidation. Causally bridging dendritic spine dynamics and associative memory is still limited by the suitable tools to measure and control spine dynamics in vivo under behaviorally relevant conditions. Here, we review data providing evidence for the remodeling of dendritic spines during associative memory processing and outline open questions. [ABSTRACT FROM AUTHOR]

Autobiographical memories are never isolated episodes; they are embedded in a network that is continually updated and prediction driven. We present autobiographical memory as a meaning‐driven process that includes both veridical traces and reconstructive schemas. Our developmental approach delineates how autobiographical memory develops across childhood and throughout adulthood, and our sociocultural approach examines the ways in which autobiographical memories are shaped by everyday social interactions embedded within cultural worldviews. These approaches are enhanced by a focus on autobiographical memory functions, namely self‐coherence, social embeddedness, and directing future behaviors. Neuroscience models of memory outlined in multiple trace and trace transformation theories and perceptual principles of predictive processing establish mechanisms and frameworks into which autobiographical memory processes are incorporated. Rather than conceptualizing autobiographical and episodic memories as accurate versus error‐prone, we frame memory as a dynamic process that is continuously updated to create coherent meaning for individuals living in complex sociocultural worlds. Autobiographical memory is a process of both accuracy and error, an intricate weaving of specific episodic details, inferences and confusions among similar experiences; it incorporates post‐event information through reminiscing and conversations, in the service of creating more meaningful coherent memories that define self, others, and the world. This article is categorized under:Psychology > Memory [ABSTRACT FROM AUTHOR]

• Hippocampal β-adrenergic system modulates reconsolidation of recognition memories. • Infusion of propranolol in the hippocampus impairs updating recognition memory trace. • Propranolol may affect elemental and conjunctive components of the memory. Targeting reconsolidation with propranolol, a blocker of β-adrenergic receptors (β-ARs), emerged as a potential treatment for maladaptive memories such as those involved in posttraumatic stress disorder (PTSD). Reconsolidation targeting treatments for PTSD are becoming a common practice in the clinic and it is important to unveil any side effects upon 'non-targeted' memories. While previous studies have focused on propranolol's effects on the reconsolidation of emotional/distressful memories, the present study asked whether propranolol is involved in the reconsolidation of recognition memories - by assessing its effects on distinct memory components and the role of the dorsal hippocampus. Rats performed an object recognition (OR) task where they were exposed to different objects: A and B presented during the sample phase; A and C presented during the reactivation phase; and D in combination of either A, B, or C during a final test. Intra-hippocampal injections of propranolol (5 µg or 10 µg) were conducted immediately after the reactivation session. Propranolol infusions consistently impaired the addition of novel information to the previously consolidated memory trace regardless of dose, and the retention of familiar objects was not affected. Higher doses of propranolol also hindered memory of a familiar object that was not presented during the reactivation session, but was previously placed at the same location where novel information was presented during reactivation. The present results shed light on the role of β-ARs on the reconsolidation of different memory components and argue for the need for further studies examining possible recognition memory deficits following propranolol treatment. [ABSTRACT FROM AUTHOR]