RESUMO
Consolidation and reconsolidation are independent memory processes. Consolidation stabilizes new memories, whereas reconsolidation restabilizes memories destabilized when reactivated during recall. However, the biological role of the destabilization/reconsolidation cycle is still unknown. It has been hypothesized that reconsolidation links new information with reactivated memories, but some reports suggest that new and old memories are associated through consolidation mechanisms instead. Object-recognition memory (ORM) serves to judge the familiarity of items and is essential for remembering previous events. We took advantage of the fact that ORM consolidation, destabilization, and reconsolidation can be pharmacologically dissociated to demonstrate that, depending on the activation state of hippocampal dopamine D1/D5 receptors, the memory of a novel object presented during recall of the memory of a familiar one can be formed via reconsolidation or consolidation, but only reconsolidation can link them. We also found that recognition memories formed through reconsolidation can be destabilized even if indirectly reactivated. Our results indicate that dopamine couples novelty detection with memory destabilization to determine whether a new recognition trace is associated with an active network and suggest that declarative reminders should be used with caution during reconsolidation-based psychotherapeutic interventions.
Assuntos
Dopamina/metabolismo , Hipocampo/metabolismo , Consolidação da Memória , Rememoração Mental , Animais , Masculino , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D5/metabolismo , Reconhecimento PsicológicoRESUMO
Most memories of life experiences will be forgotten or modified over time. Although several studies have investigated the processes underlying memory formation, the mechanisms behind memory updating and forgetting remain unclear. The endocannabinoid system has been shown to be closely involved in various memory processes such as consolidation, destabilization, and extinction. Here, we investigate the role of the endocannabinoid system in memory updating, behavioral flexibility, and forgetting. We found that the hippocampal infusion of CB1 antagonist prevented memory updating in the immediate footshock (context pre-exposure facilitation effect) and reversal learning. Also, CB1 antagonist accelerated forgetting in inhibitory avoidance. Thus, by indicating the important role played by the endocannabinoid system, our results extend current knowledge of the mechanisms underpinning memory updating and forgetting.
Assuntos
Endocanabinoides , Memória , HipocampoRESUMO
In the last decade it became clear that a previously consolidated memory can be modified during the plastic state induced by retrieval. This updating process opens the possibility to adapt undesired memory. Here we investigated whether fear memory could be updated to less-aversive/positive level by inserting hedonic information during retrieval. Considering that methylphenidate has strong rewarding propriety, we injected 3 or 10 mg/kg pre or post-reactivation in rats previously trained in contextual fear conditioning. We found that memory reactivation under effect of methylphenidate attenuates fear memory within-session and in subsequent tests in a drug-free condition, without presenting spontaneous recovery. Interestingly, methylphenidate impaired memory extinction when injected before, but not after a long reactivation session. We also showed that methylphenidate induces place preference and increases motor activity. Thus, this study provides new insights in the memory updating process and suggests that a previously consolidated fear memory can be attenuated by inserting appetitive information during retrieval.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Medo/efeitos dos fármacos , Medo/psicologia , Memória/efeitos dos fármacos , Metilfenidato/farmacologia , Recompensa , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Masculino , Consolidação da Memória , Rememoração Mental/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Prazer , Ratos , Ratos WistarRESUMO
Consolidated memory can be again destabilized by the presentation of a memory cue (reminder) of the previously acquired information. During this process of labilization/restabilization memory traces can be either impaired, strengthened or updated in content. Here, we study if a consolidated memory can be updated by linking one original cue to two different outcomes and whether this process was modulated by the GABAergic system. To aim that, we designed two experiments carried out in three consecutive days. All participants learned a list of non-sense syllable pairs on day 1. On day 2 the new information was introduced after the reminder or no-reminder presentation. Participants were tested on day 3 for the updated or original list (Exp. 1). In Exp. 2 we tested whether this new information was incorporated by an inhibitory process mediated by the GABAergic system. For that, participants retrieved the original information before being taken Clonazepam 0.25mg (GABAA agonist) or Placebo pill. We found that the groups that received the reminder correctly recalled the old and new information. However, the no reminder groups only correctly recalled the original information. Furthermore, when testing occurred in the presence of Clonazepam, the group that received the reminder plus the new information showed an impaired original memory performance compared to the group that received only Clonazepam (without reminder) or the reminder plus Placebo pill. These results show that new information can be added to a reactivated declarative memory in humans by linking one cue to two different outcomes. Furthermore, we shed light on the mechanisms of memory updating being the GABAergic system involved in the modulation of the old and new information expression.
Assuntos
Clonazepam/farmacologia , Moduladores GABAérgicos/farmacologia , Consolidação da Memória/efeitos dos fármacos , Memória/efeitos dos fármacos , Adolescente , Adulto , Sinais (Psicologia) , Feminino , Humanos , Masculino , Adulto JovemRESUMO
During memory retrieval, consolidated memories are expressed and destabilized in order to maintain or update information through a memory reconsolidation process. Despite the key role of the amygdala during memory acquistion and consolidation, the participation of neurotransmitter signals in memory retrieval is poorly understood. Hence, we used conditioned taste aversion and in vivo microdialysis to evaluate changes in glutamate, norepinephrine and dopamine concentrations within the amygdala during memory retrieval. We observed that exposure to an aversive-conditioned stimulus induced an augmentation in glutamate, norepinephrine and dopamine levels within the amygdala, while exposure to a familiar and safe stimulus did not induce changes in these neurotransmitters levels. Also, we evaluated the amygdalar blockade of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), ß-adrenergic and dopamine D1 receptors in memory retrieval and updating. Results showed that during retrieval, behavioural expression was impaired by intra-amygdalar blockade of AMPA and ß-adrenergic receptors, whereas NMDA, D1 and ß-adrenergic receptors blockade hindered memory updating. In summary, during conditioned taste aversion retrieval there was an increase in the extracellular levels of glutamate, norepinephrine and dopamine within the amygdala, and their receptors activity were differentially involved in the behavioural expression and memory updating during retrieval.