Differential neurophysiological correlates of retrieval of consolidated and reconsolidated memories in humans: An ERP and pupillometry study.

Consolidated memories can return to a labile state if they are reactivated by unpredictable reminders. To persist, active memories must be re-stabilized through a process known as reconsolidation. Although there is consistent behavioral evidence about this process in humans, the retrieval process of reconsolidated memories remains poorly understood. In this context, one fundamental question is whether the same or different neurophysiological mechanisms are involved in retrieval of consolidated and reconsolidated memories. Because it has been demonstrated that the exposure to the reconsolidation process may restructure and strengthen memories, we hypothesized distinct neurophysiological patterns during retrieval of reconsolidated memories. In addition, we hypothesized that interfering with the reconsolidation process using a new learning can prevent these neurophysiological changes. To test it, consolidated, reconsolidated and declarative memories whose reconsolidation process was interfered (i.e., picture-word pairs) were evaluated in humans in an old/new associative recall task while the brain activity and the pupillary response were recorded using electroencephalography and eyetracking. Our results showed that retrieval of reconsolidated memories elicits specific patterns of brain activation, characterized by an earlier peak latency and a smaller magnitude of the left parietal ERP old/new effect compared to memories that were only consolidated or whose reconsolidation process was interfered by a new learning. Moreover, our results demonstrated that only retrieval of reconsolidated memories is associated with a late reversed mid-frontal effect in a 600-690 time window. Complementarily, memories that were reactivated showed an earlier peak latency of the pupil old/new effect compared to non-reactivated memories. These findings support the idea that reconsolidation has an important impact in how memories are retrieved in the future, showing that retrieval of reconsolidated memories is partially supported by specific brain mechanisms.

Enhancing a declarative memory in humans: the effect of clonazepam on reconsolidation.

A consolidated memory recalled by a specific reminder can become unstable (labile) and susceptible to facilitation or impairment for a discrete period of time. This labilization phase is followed by a process of stabilization called reconsolidation. The phenomenon has been shown in diverse types of memory, and different pharmacological agents have been used to disclose its presence. Several studies have revealed the relevance of the GABAergic system to this process. Consequently, our hypothesis is that the system is involved in the reconsolidation of declarative memory in humans. Thus, using our verbal learning task, we analyzed the effect of benzodiazepines on the re-stabilization of the declarative memory. On Day 1, volunteers learned an association between five cue- response-syllables. On Day 2, the verbal memory was labilized by a reminder presentation, and then a placebo capsule or 0.25 mg or 0.03 mg of clonazepam was administered to the subjects. The verbal memory was evaluated on Day 3. The volunteers who had received the 0.25 mg clonazepam along with the specific reminder on Day 2, exhibited memory improvement. In contrast, there was no effect when the drug was given without retrieval, when the memory was simply retrieved instead of being reactivated or when short-term memory testing was performed 4 h after reactivation. We discuss the GABAergic role in reconsolidation, which shows a collateral effect on other memories when the treatment is aimed at treating anxiety disorders. Further studies might elucidate the role of GABA in the reconsolidation process associated with dissimilar scenarios. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Human reconsolidation does not always occur when a memory is retrieved: the relevance of the reminder structure.

Memory reconsolidation is defined as a process in which the retrieval of a previously consolidated memory returns to a labile state which is then subject to stabilization. The reminder is the event that begins with the presentation of the learned cue and triggers the labilization-reconsolidation process. Since the early formulation of the hypothesis, several controversial items have arisen concerning the conditions that define reconsolidation. It is herein proposed that two diagnostic features characterize reconsolidation, namely: the labilization of the reactivated memory and the specificity of the reminder structure. To study this proposal, subjects received two different training sessions on verbal material on Day 1 and Day 2, respectively. Finally, they were tested for the first and second acquired memories on Day 3. It is demonstrated that the human declarative memory fulfills the two requirements that define the process. First, the reactivated memory is impaired by a new learning only when it is given closely after the reminder, revealing that the memory is labilized. Second, the omission of at least one of the reminder's components prevents labilization. Therefore, results show that the new learning fails to produce an amnesic effect on the target memory either when the reminder omits the learned cue or includes the beginning of the reinforcement.