The Experts below are selected from a list of 4935 Experts worldwide ranked by ideXlab platform
Karim Nader - One of the best experts on this subject based on the ideXlab platform.
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noradrenergic projections from the locus coeruleus to the amygdala constrain fear memory Reconsolidation
eLife, 2020Co-Authors: Josue Haubrich, Matteo Bernabo, Karim NaderAbstract:Memory Reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we investigated the hypothesis that specific modulatory signals shape memory formation into a state that is Reconsolidation-resistant. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala of rats. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo Reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on Reconsolidation is set at the time of encoding by the action of the NOR-LC.
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noradrenergic projections from the locus coeruleus to the amygdala constrain auditory fear memory Reconsolidation
bioRxiv, 2020Co-Authors: Josue Haubrich, Matteo Bernabo, Karim NaderAbstract:Memory Reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we extend the understanding of the mechanisms implicated in Reconsolidation-resistant memories by investigating the hypothesis that specific modulatory signals shape memory formation into a state that lacks lability. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo Reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on Reconsolidation is set at the time of encoding by the action of the NOR-LC.
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Reconsolidation and the dynamic nature of memory
Cold Spring Harbor Perspectives in Biology, 2015Co-Authors: Karim NaderAbstract:Research on the Reconsolidation effect was greatly revitalized by the highly analytic demonstration of memory Reconsolidation (Nader et al. 2000) in a well-defined behavioral protocol (auditory fear conditioning in the rat). Since this study, Reconsolidation has been demonstrated in hundreds of studies over a range of species, tasks, and amnesic agents. Evidence for Reconsolidation does not come solely from the behavioral level of analysis. Cellular and molecular correlates of Reconsolidation have also been found. In this review I will first define the evidence on which Reconsolidation is concluded to exist. I will then discuss some of the conceptual issues facing the field in determining when Reconsolidation does and does not occur. Lastly I will explain the clinical implications of this effect.
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Reconsolidation of human memory brain mechanisms and clinical relevance
Biological Psychiatry, 2014Co-Authors: Lars Schwabe, Karim Nader, Jens C PruessnerAbstract: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.
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preclinical evaluation of Reconsolidation blockade by clonidine as a potential novel treatment for posttraumatic stress disorder
Neuropsychopharmacology, 2012Co-Authors: Karine Gamache, Roger K Pitman, Karim NaderAbstract:Exposure to traumatic events can lead to posttraumatic stress disorder (PTSD). Current PTSD treatments typically only produce partial improvement. Hence, there is a need for preclinical research to identify new candidate drugs and to develop novel therapeutic approaches. Animal studies have indicated that fear memories can be weakened by blocking restabilization after retrieval, a process known as Reconsolidation. Furthermore, evidence suggests that there are important alterations of the noradrenergic system in PTSD, and hence it may be of interest to study drugs that target this pathway. Here, we investigated the efficacy of clonidine, an α2-adrenoreceptor agonist, to block Reconsolidation in an animal model of persistent traumatic memories. Using an auditory fear conditioning paradigm in rats, we tested the efficacy of clonidine to weaken fear memory retention when administered systemically after retrieval. We evaluated dosage, number of treatments, and specificity in Reconsolidation blockade. We found that postretrieval administration of clonidine disrupts fear-related memories in a dose-dependent manner and that two treatments are sufficient for maximal memory impairment. Furthermore, we determined that this effect is long lasting and specific to Reconsolidation processes as shown by the selectivity to affect reactivated memories and the absence of spontaneous recovery and of postreactivation short-term memory impairment. Our results demonstrate the efficacy of systemic administration of clonidine following retrieval to persistently disrupt fear memory retention through Reconsolidation blockade. This study provides important preclinical parameters for future therapeutic strategies involving clonidine to block Reconsolidation as a novel treatment for PTSD symptoms.
Jonathan L C Lee - One of the best experts on this subject based on the ideXlab platform.
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updating memories the role of prediction errors in memory Reconsolidation
Behavioural Brain Research, 2015Co-Authors: Marc T J Extonmcguinness, Jonathan L C Lee, Amy C ReicheltAbstract:Memories are not static imprints of past experience, but rather are dynamic entities which enable us to predict outcomes of future situations and inform appropriate behaviours. In order to maintain the relevance of existing memories to our daily lives, memories can be updated with new information via a process of Reconsolidation. In this review we describe recent experimental advances in the Reconsolidation of both appetitive and aversive memory, and explore the neuronal mechanisms that underpin the conditions under which Reconsolidation will occur. We propose that a prediction error signal, originating from dopaminergic midbrain neurons, is necessary for destabilisation and subsequent Reconsolidation of a memory.
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divergent cellular pathways of hippocampal memory consolidation and Reconsolidation
Hippocampus, 2013Co-Authors: Jonathan L C Lee, Robert E HyndsAbstract:The Reconsolidation of memories after their retrieval involves cellular mechanisms that recapitulate much of the initial consolidation process. However, we have previously demonstrated that there are independent cellular mechanisms of consolidation and Reconsolidation in the dorsal hippocampus for contextual fear memories. Expression of BDNF was required for consolidation, while Zif268 expression was necessary for Reconsolidation. Given the dichotomy between the obvious mechanistic similarity and notable dissociations between consolidation and Reconsolidation, we sought to determine whether the separation at the level of gene expression reflected either parallel and independent upstream signaling pathways, or common upstream mechanisms that diverge by the level of transcriptional activation. Here we show that while consolidation and Reconsolidation are commonly dependent upon NMDA receptor activation in the dorsal hippocampus there is a double dissociation between the effects of the MEK inhibitor U0126 and the IKK inhibitor sulfasalazine. Moreover, rescue experiments and western blot analyses show that there are functional NMDA receptor-ERK1-BDNF and NMDA receptor-IKKα-Zif268 pathways for consolidation and Reconsolidation, respectively. Therefore, there are divergent pathways of hippocampal memory consolidation and Reconsolidation, involving commonality at the cell surface, but separable downstream kinase cascades and transcriptional regulation.
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The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory Reconsolidation.
Learn Mem, 2010Co-Authors: Florence R M Théberge, Jonathan L C Lee, Amy L Milton, David Belin, Barry J. EverittAbstract:A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and Reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory Reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the basolateral amygdala in the Reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory Reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the Reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where Reconsolidation of a cue-drug memory occurs. However Reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.
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appetitive memory Reconsolidation depends upon nmda receptor mediated neurotransmission
Neurobiology of Learning and Memory, 2008Co-Authors: Jonathan L C Lee, Barry J. EverittAbstract:Abstract Memory persistence is a dynamic process involving the Reconsolidation of memories after their reactivation. Reconsolidation impairments have been demonstrated for many types of memories in rats, and signaling at N -methyl- d -aspartate (NMDA) receptors appears often to be a critical pharmacological mechanism. Here we investigated the Reconsolidation of appetitive pavlovian memories reinforced by natural rewards. In male Lister Hooded rats, systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro- SH -dibenzo{ a , d }cyclohepten-5,10-imine maleate (MK-801, 0.1 mg/kg i.p.) either before or immediately following a brief memory reactivation session abolished the subsequent acquisition of a new instrumental response with sucrose conditioned reinforcement. However, only when injected prior to memory reactivation was MK-801 effective in disrupting the maintenance of a previously-acquired instrumental response with conditioned reinforcement. These results demonstrate that NMDA receptor-mediated signaling is required for appetitive pavlovian memory Reconsolidation.
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disrupting Reconsolidation of drug memories reduces cocaine seeking behavior
Neuron, 2005Co-Authors: Jonathan L C Lee, Kerrie L. Thomas, Patricia Di Ciano, Barry J. EverittAbstract:Maladaptive memories that associate environmental stimuli with the effects of drugs of abuse are known to be a major cause of relapse to, and persistence of, a drug addictive habit. However, memories may be disrupted after their acquisition and consolidation by impairing their Reconsolidation. Here, we show that infusion of Zif268 antisense oligodeoxynucleotides into the basolateral amygdala, prior to the reactivation of a well-learned memory for a conditioned stimulus (CS)-cocaine association, abolishes the acquired conditioned reinforcing properties of the drug-associated stimulus and thus its impact on the learning of a new cocaine-seeking response. Furthermore, we show that Reconsolidation of CS-fear memories also requires Zif268 in the amygdala. These results demonstrate that appetitive CS-drug memories undergo Reconsolidation in a manner similar to aversive memories and that this amygdala-dependent Reconsolidation can be disrupted to reduce the impact of drug cues on drug seeking.
Barry J. Everitt - One of the best experts on this subject based on the ideXlab platform.
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a novel retrieval dependent memory process revealed by the arrest of erk1 2 activation in the basolateral amygdala
The Journal of Neuroscience, 2018Co-Authors: Emiliano Merlo, Amy L Milton, Barry J. EverittAbstract:Fully consolidated fear memories can be maintained or inhibited by retrieval-dependent mechanisms depending on the degree of re-exposure to fear cues. Short exposures promote memory maintenance through Reconsolidation and long exposures promote inhibition through extinction. Little is known about the neural mechanisms by which increasing cue exposure overrides Reconsolidation and instead triggers extinction. Using auditory fear conditioning in male rats, we analysed the role of a molecular mechanism common to Reconsolidation and extinction of fear, ERK1/2 activation within the basolateral amygdala (BLA), after intermediate CS exposure events. We show that an intermediate re-exposure (4 CS presentations) failed to activate ERK1/2 in the BLA, suggesting the absence of Reconsolidation or extinction mechanisms. Supporting this hypothesis, pharmacologically inhibiting the BLA ERK1/2-dependent signalling pathway in conjunction with 4 CS presentations had no effect on fear expression, and the NMDA receptor partial agonist D-cycloserine, which enhanced extinction and ERK1/2 activation in partial extinction protocols (7 CSs), had no behavioural or molecular effect when given in association with 4 CS presentations. These molecular and behavioural data reveal a novel retrieval-dependent memory phase occurring along the transition between conditioned fear maintenance and inhibition. CS-dependent molecular events in the BLA may arrest Reconsolidation intracellular signalling mechanism in an extinction-independent manner. These findings are critical for understanding the molecular underpinnings of fear memory persistence after retrieval both in health and disease. SIGNIFICANCE STATEMENT Consolidated fear memories can be altered by retrieval-dependent mechanisms. Whereas a brief conditioned stimulus (CS) exposure promotes fear memory maintenance through Reconsolidation, a prolonged exposure engages extinction and fear inhibition. The nature of this transition and whether an intermediate degree of CS exposure engages Reconsolidation or extinction is unknown. We show that an intermediate cue exposure session (4 CSs) produces the arrest of ERK1/2 activation in the basolateral amygdala, a common mechanism for Reconsolidation and extinction. Amnestic or hypermnestic treatments given in association with 4 CSs had no behavioural or molecular effects, respectively. This evidence reveals a novel retrieval-dependent memory phase. Intermediate degrees of CS exposure fail to trigger Reconsolidation or extinction, leaving the original memory in an insensitive state.
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Reconsolidation and extinction are dissociable and mutually exclusive processes behavioral and molecular evidence
The Journal of Neuroscience, 2014Co-Authors: Emiliano Merlo, Amy L Milton, Zara Y Goozee, David E H Theobald, Barry J. EverittAbstract:Memory persistence is critically influenced by retrieval. In rats, a single presentation of a conditioned fear stimulus induces memory Reconsolidation and fear memory persistence, while repeated fear cue presentations result in loss of fear through extinction. These two opposite behavioral outcomes are operationally linked by the number of cue presentations at memory retrieval. However, the behavioral properties and mechanistic determinants of the transition have not yet been explored; in particular, whether Reconsolidation and extinction processes coexist or are mutually exclusive, depending on the exposure to non-reinforced retrieval events. We characterized both behaviorally and molecularly the transition from Reconsolidation to extinction of conditioned fear and showed that an increase in calcineurin (CaN) in the basolateral amygdala (BLA) supports the shift from fear maintenance to fear inhibition. Gradually increasing the extent of retrieval induces a gradual decrease in freezing responses to the conditioned stimulus and a gradual increase in amygdala CaN level. This newly synthesized CaN is required for the extinction, but not the Reconsolidation, of conditioned fear. During the transition from Reconsolidation to extinction, we have revealed an insensitive state of the fear memory where NMDA-type glutamate receptor agonist and antagonist drugs are unable either to modulate CaN levels in the BLA or alter the Reconsolidation or extinction processes. Together, our data indicate both that Reconsolidation and extinction are mutually exclusive processes and also reveal the presence of a transitional, or “limbo,” state of the original memory between these two alternative outcomes of fear memory retrieval, when neither process is engaged.
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The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory Reconsolidation.
Learn Mem, 2010Co-Authors: Florence R M Théberge, Jonathan L C Lee, Amy L Milton, David Belin, Barry J. EverittAbstract:A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and Reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory Reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the basolateral amygdala in the Reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory Reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the Reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where Reconsolidation of a cue-drug memory occurs. However Reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.
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appetitive memory Reconsolidation depends upon nmda receptor mediated neurotransmission
Neurobiology of Learning and Memory, 2008Co-Authors: Jonathan L C Lee, Barry J. EverittAbstract:Abstract Memory persistence is a dynamic process involving the Reconsolidation of memories after their reactivation. Reconsolidation impairments have been demonstrated for many types of memories in rats, and signaling at N -methyl- d -aspartate (NMDA) receptors appears often to be a critical pharmacological mechanism. Here we investigated the Reconsolidation of appetitive pavlovian memories reinforced by natural rewards. In male Lister Hooded rats, systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro- SH -dibenzo{ a , d }cyclohepten-5,10-imine maleate (MK-801, 0.1 mg/kg i.p.) either before or immediately following a brief memory reactivation session abolished the subsequent acquisition of a new instrumental response with sucrose conditioned reinforcement. However, only when injected prior to memory reactivation was MK-801 effective in disrupting the maintenance of a previously-acquired instrumental response with conditioned reinforcement. These results demonstrate that NMDA receptor-mediated signaling is required for appetitive pavlovian memory Reconsolidation.
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disrupting Reconsolidation of drug memories reduces cocaine seeking behavior
Neuron, 2005Co-Authors: Jonathan L C Lee, Kerrie L. Thomas, Patricia Di Ciano, Barry J. EverittAbstract:Maladaptive memories that associate environmental stimuli with the effects of drugs of abuse are known to be a major cause of relapse to, and persistence of, a drug addictive habit. However, memories may be disrupted after their acquisition and consolidation by impairing their Reconsolidation. Here, we show that infusion of Zif268 antisense oligodeoxynucleotides into the basolateral amygdala, prior to the reactivation of a well-learned memory for a conditioned stimulus (CS)-cocaine association, abolishes the acquired conditioned reinforcing properties of the drug-associated stimulus and thus its impact on the learning of a new cocaine-seeking response. Furthermore, we show that Reconsolidation of CS-fear memories also requires Zif268 in the amygdala. These results demonstrate that appetitive CS-drug memories undergo Reconsolidation in a manner similar to aversive memories and that this amygdala-dependent Reconsolidation can be disrupted to reduce the impact of drug cues on drug seeking.
Antoine Besnard - One of the best experts on this subject based on the ideXlab platform.
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comparative dynamics of mapk erk signalling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval
Brain Structure & Function, 2014Co-Authors: Antoine Besnard, Serge Laroche, Jocelyne CabocheAbstract:Over the past few years multiple studies have attempted to uncover molecular signatures of memory Reconsolidation when compared to consolidation. In the present study we used immunocytochemical detection of the MAPK/ERK1/2 pathway, to track activated neuronal circuits in the hippocampus and amygdala recruited during the consolidation and Reconsolidation of a contextual fear conditioning (CFC) memory. We report selective differences in magnitude and temporal dynamics of activated ERK1/2 signalling in different subregions of these two structures between the post-training and post-retrieval periods, except in the dentate gyrus, where the patterns of activation were similar. We then focused on this brain area to dissect out the patterns of downstream ERK1/2 signalling components, including the phosphorylation of MSK-1 and histone H3 on ser10, along with the induction of the Immediate Early Genes (IEGs) Arc/Arg3.1, c-Fos and Zif268/Egr1 following CFC training and retrieval. We found that the completion of the nucleosomal response as well as the induction of IEGs shorter during the Reconsolidation period as compared to consolidation. Our results shed new light on the cellular mechanisms underlying the consolidation and Reconsolidation processes engaged following CFC training and retrieval and further extend the notion that memory Reconsolidation is not mechanistically a repetition of consolidation. In addition, we provide evidence that the strength of a previously established CFC memory is characterized by distinct patterns of ERK1/2 activation in different hippocampal and amygdalar subfields upon CFC memory recall. Our results emphasize the differences between consolidation and Reconsolidation processes in relation to contextual fear memories.
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Recall and Reconsolidation of contextual fear memory : differential control by ERK and Zif268 Expression Dosage.
PLoS ONE, 2013Co-Authors: Antoine Besnard, Jocelyne Caboche, Serge LarocheAbstract:Compelling evidence points to the existence of independent cellular processes involved in the consolidation and Reconsolidation of memory. For instance, a double dissociation has been reported between hippocampal Extracellular-Regulated Kinase-1/2 (ERK1/2) activity being necessary for contextual fear conditioning (CFC) consolidation but not Reconsolidation. Conversely, hippocampal expression of the immediate early gene Zif268 is necessary for CFC Reconsolidation but not consolidation. Since we previously reported that ERK1/2 controls the transcription of Zif268 in the hippocampus, we examined the precise role of ERK1/2 activity and Zif268 gene expression dosage in CFC memory processing. For this, we first assessed performance of Zif268 homozygous and heterozygous mutant mice in a CFC paradigm. Whereas Zif268−/− mice displayed a deficit of both consolidation and Reconsolidation, Zif268+/− mice displayed a selective deficit of Reconsolidation only, therefore pointing to the relationship between Zif268 gene expression dosage and CFC memory processing. Zif268 gene expression dosage interfered with the Reconsolidation process if and only if CFC memory was relatively recently encoded and directly reactivated. Furthermore, CFC memory strengthening previously reported to involve Zif268 expression in the hippocampus was spared in Zif268+/− mice. Finally, blocking ERK1/2 activity prior to CFC retrieval prevented the deficit of Reconsolidation observed in Zif268+/− mice. Collectively, these results highlight a tight relationship between Zif268 gene expression dosage and CFC memory processing. They also suggest that ERK1/2 activity upon CFC memory recall is necessary for its retrieval, a prerequisite for its reactivation and subsequent Reconsolidation.
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Reconsolidation of memory: A decade of debate
Progress in Neurobiology, 2012Co-Authors: Antoine Besnard, Jocelyne Caboche, Serge LarocheAbstract:Memory consolidation refers to a slow process that stabilises a memory trace after initial acquisition of novel events. The consolidation theory posits that once a memory is stored in the brain, it remains fixed for the lifetime of the memory. However, compelling evidence has suggested that upon recall, memories can re-enter a state of transient instability, requiring further stabilisation to be available once again for recall. Since its rehabilitation in the past ten years, this process of Reconsolidation of memory after recall stimulated intense debates in the field of cognitive neuroscience In this review we compile this plentiful literature with a particular emphasis on some of the key questions that have emerged from the Reconsolidation theory. We focus on tracing the characterisation of the boundary conditions that constrain the occurrence of memory Reconsolidation. We also discuss accumulating evidence supporting the idea that Reconsolidation, as implied by its definition, is not a mere repetition of consolidation. We review seminal studies that uncovered specific mechanisms recruited during Reconsolidation that are not always crucially involved in consolidation. We next address the physiological significance of Reconsolidation since several lines of evidence support the idea that Reconsolidation, as opposed to consolidation, may offer a unique opportunity to update memories. We finally discuss recent evidence for or against the potential that the process of memory Reconsolidation offers for ongoing efforts to develop novel strategies to combat pathogenic memories.
Jorge Alberto Quillfeldt - One of the best experts on this subject based on the ideXlab platform.
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Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus
Frontiers Media S.A., 2019Co-Authors: Pablo Javier Espejo, Natividade De Sá Couto-pereira, Carine Lampert, Aline Dos Santos Vieira, Camilla Lazzaretti, Grasielle Clotildes Kincheski, Victor Alejandro Molina, Jorge Alberto QuillfeldtAbstract:Early life experiences program lifelong responses to stress. In agreement, resilience and vulnerability to psychopathologies, such as posttraumatic stress disorder (PTSD), have been suggested to depend on the early background. New therapies have targeted memory Reconsolidation as a strategy to modify the emotional valence of traumatic memories. Here, we used animal models to study the molecular mechanism through which early experiences may later affect aversive memory Reconsolidation. Handling (H)—separation of pups from dams for 10 min—or maternal separation (MS) — 3-h separation—were performed from PDN1–10, using non-handled (NH) litters as controls. Adult males were trained in a contextual fear conditioning (CFC) task; 24 h later, a short reactivation session was conducted in the conditioned or in a novel context, followed by administration of midazolam 3 mg/kg i.p. (mdz), known to disturb Reconsolidation, or vehicle; a test session was performed 24 h after. The immunocontent of relevant proteins was studied 15 and 60 min after memory reactivation in the dorsal hippocampus (dHc) and basolateral amygdala complex (BLA). Mdz-treated controls (NH) showed decreased freezing to the conditioned context, consistent with Reconsolidation impairment, but H and MS were resistant to labilization. Additionally, MS males showed increased freezing to the novel context, suggesting fear generalization; H rats showed lower freezing than the other groups, in accordance with previous suggestions of reduced emotionality facing adversities. Increased levels of Zif268, GluN2B, β-actin and polyubiquitination found in the BLA of all groups suggest that memory Reconsolidation was triggered. In the dHc, only NH showed increased Zif268 levels after memory retrieval; also, a delay in ERK1/2 activation was found in H and MS animals. We showed here that Reconsolidation of a contextual fear memory is insensitive to interference by a GABAergic drug in adult male rats exposed to different neonatal experiences; surprisingly, we found no differences in the Reconsolidation process in the BLA, but the dHc appears to suffer temporal desynchronization in the engagement of Reconsolidation. Our results support a hippocampal-dependent mechanism for Reconsolidation resistance in models of early experiences, which aligns with current hypotheses for the etiology of PTSD
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involvement of the infralimbic cortex and ca1 hippocampal area in Reconsolidation of a contextual fear memory through cb1 receptors effects of cp55 940
Neurobiology of Learning and Memory, 2016Co-Authors: Fabiana Santana, Lindsey De Freitas Cassini, Rodrigo O Sierra, Josue Haubrich, Ana Paula Crestani, Lucas De Oliveira Alvares, Johanna M Duran, Jorge Alberto QuillfeldtAbstract:The endocannabinoid system (ECS) has a pivotal role in different cognitive functions such as learning and memory. Recent evidence confirm the involvement of the hippocampal CB1 receptors in the modulation of both memory extinction and Reconsolidation processes in different brain areas, but few studies focused on the infralimbic cortex, another important cognitive area. Here, we infused the cannabinoid agonist CP55,940 either into the infralimbic cortex (IL) or the CA1 area of the dorsal hippocampus (HPC) of adult male Wistar rats immediately after a short (3min) reactivation session, known to labilize a previously consolidated memory trace in order to allow its Reconsolidation with some modification. In both structures, the treatment was able to disrupt Reconsolidation in a relatively long lasting way, reducing the freezing response. To our notice, this is the first demonstration of ECS involvement in Reconsolidation in the Infralimbic Cortex. Despite poorly discriminative between CB1 and CB2 receptors, CP55,940 is a potent agent, and these results suggest that a similar CB1-dependent circuitry is at work both in HPC and in the IL during memory Reconsolidation.
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memory Reconsolidation allows the consolidation of a concomitant weak learning through a synaptic tagging and capture mechanism
Hippocampus, 2013Co-Authors: Lindsey De Freitas Cassini, Rodrigo O Sierra, Josue Haubrich, Ana Paula Crestani, Fabiana Santana, Lucas De Oliveira Alvares, Jorge Alberto QuillfeldtAbstract:Motivated by the synaptic tagging and capture (STC) hypothesis, it was recently shown that a weak learning, only able to produce short-term memory (STM), can succeed in establishing long- term memory (LTM) with a concomitant, stronger experience. This is consistent with the capture, by the first-tagged event, of the so-called plasticity-related proteins (PRPs) provided by the second one. Here, we describe how a concomitant session of reactivation/Reconsolidation of a stronger, contextual fear conditioning (CFC) memory, allowed LTM to result from a weak spatial object recognition (wSOR) training. Consist- ent with an STC process, the effect was observed only during a critical time window and was dependent on the CFC Reconsolidation-related protein synthesis. Retrieval by itself (without Reconsolidation) did not have the same promoting effect. We also found that the inactivation of the NMDA receptor by AP5 prevented wSOR training to receive this support of CFC Reconsolidation (supposedly through the production of PRPs), which may be the equivalent of blocking the setting of a learning tag in the dorsal CA1 region for that task. Furthermore, either a Water Maze Reconsolidation, or a CFC extinction session, allowed the forma- tion of wSOR-LTM. These results suggest for the first time that a recon- solidation session can promote the consolidation of a concomitant weak learning through a probable STC mechanism. These findings allow new insights concerning the influence of Reconsolidation in the acquisition of memories of otherwise unrelated events during daily life situations. V C 2013 Wiley Periodicals, Inc.
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reactivation enables memory updating precision keeping and strengthening exploring the possible biological roles of Reconsolidation
Neuroscience, 2013Co-Authors: Lucas De Oliveira Alvares, Lindsey De Freitas Cassini, Josue Haubrich, Ana Paula Crestani, Fabiana Santana, Jorge Alberto QuillfeldtAbstract:Although much has been learned regarding the molecular and cellular mechanisms of memory Reconsolidation, its actual biological function remains unclear. In this work we investigate the possibility that three different mnemonic processes - updating, precision-keeping and trace strengthening - are mediated by Reconsolidation in contextual fear conditioning. Reconsolidation involves the activation of calcium channels for the destabilization during the reactivation. Our results show that when memory is reactivated in a situation that does not match the original information, content is modified, i.e., "updated". However, when the contextual condition matches the original one, memory reactivation contributes either to its strengthening or to the maintenance of its precision content over time. Since the L-type voltage-gated calcium channel antagonist nimodipine blocked these effects, we suggest that Reconsolidation is the mechanism supporting these processes.
