New Episodic Learning Interferes with the Reconsolidation of Autobiographical Memories

It is commonly assumed that, with time, an initially labile memory is transformed into a permanent one via a process of consolidation. Yet, recent evidence indicates that memories can return to a fragile state again when reactivated, requiring a period of reconsolidation. In the study described here, we found that participants who memorized a story immediately after they had recalled neutral and emotional experiences from their past were impaired in their memory for the neutral (but not for the emotional) experiences one week later. The effect of learning the story depended critically on the preceding reactivation of the autobiographical memories since learning without reactivation had no effect. These results suggest that new learning impedes the reconsolidation of neutral autobiographical memories.     

Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories

1. Download : Download high-res image (353KB)
2. Download : Download full-size image

     

Xenon Impairs Reconsolidation of Fear Memories in a Rat Model of Post-Traumatic Stress Disorder (PTSD)

Xenon (Xe) is a noble gas that has been developed for use in people as an inhalational anesthestic and a diagnostic imaging agent. Xe inhibits glutamatergic N-methyl-D-aspartate (NMDA) receptors involved in learning and memory and can affect synaptic plasticity in the amygdala and hippocampus, two brain areas known to play a role in fear conditioning models of post-traumatic stress disorder (PTSD). Because glutamate receptors also have been shown to play a role in fear memory reconsolidation – a state in which recalled memories become susceptible to modification – we examined whether Xe administered after fear memory reactivation could affect subsequent expression of fear-like behavior (freezing) in rats. Male Sprague-Dawley rats were trained for contextual and cued fear conditioning and the effects of inhaled Xe (25%, 1 hr) on fear memory reconsolidation were tested using conditioned freezing measured days or weeks after reactivation/Xe administration. Xe administration immediately after fear memory reactivation significantly reduced conditioned freezing when tested 48 h, 96 h or 18 d after reactivation/Xe administration. Xe did not affect freezing when treatment was delayed until 2 h after reactivation or when administered in the absence of fear memory reactivation. These data suggest that Xe substantially and persistently inhibits memory reconsolidation in a reactivation and time-dependent manner, that it could be used as a new research tool to characterize reconsolidation and other memory processes, and that it could be developed to treat people with PTSD and other disorders related to emotional memory.     

Hippocampus, Temporal Context and Taste Memories

Chemical Senses, 30 (suppl 1): i160–i161, 2005     

Numerical Magnitude Affects Temporal Memories but Not Time Encoding

Previous research has suggested that the perception of time is influenced by concurrent magnitude information (e.g., numerical magnitude in digits, spatial distance), but the locus of the effect is unclear, with some findings suggesting that concurrent magnitudes such as space affect temporal memories and others suggesting that numerical magnitudes in digits affect the clock speed during time encoding. The current paper reports 6 experiments in which participants perceived a stimulus duration and then reproduced it. We showed that though a digit of a large magnitude (e.g., 9), relative to a digit of a small magnitude (e.g., 2), led to a longer reproduced duration when the digits were presented during the perception of the stimulus duration, such a magnitude effect disappeared when the digits were presented during the reproduction of the stimulus duration. These findings disconfirm the account that large numerical magnitudes accelerate the speed of an internal clock during time encoding, as such an account incorrectly predicts that a large numerical magnitude should lead to a shorter reproduced duration when presented during reproduction. Instead, the findings suggest that numerical magnitudes, like other magnitudes such as space, affect temporal memories when numerical magnitudes and temporal durations are concurrently held in memory. Under this account, concurrent numerical magnitudes have the chance to influence the memory of the perceived duration when they are presented during perception but not when they are presented at the reproduction stage.     

Multiple Temporal Cluster Detection

This article proposes a simple method to determine single or multiple temporal clustering on a variable size population. By a transformation of the data set, the method based on a regression model allows consideration of a variable population size during the time of study. A model selection procedure and a resampling method are used to select the number of clusters. The results have applications in epidemiological studies of rare diseases.     

The Decay of Motor Memories Is Independent of Context Change Detection

When the error signals that guide human motor learning are withheld following training, recently-learned motor memories systematically regress toward untrained performance. It has previously been hypothesized that this regression results from an intrinsic volatility in these memories, resulting in an inevitable decay in the absence of ongoing error signals. However, a recently-proposed alternative posits that even recently-acquired motor memories are intrinsically stable, decaying only if a change in context is detected. This new theory, the context-dependent decay hypothesis, makes two key predictions: (1) after error signals are withheld, decay onset should be systematically delayed until the context change is detected; and (2) manipulations that impair detection by masking context changes should result in prolonged delays in decay onset and reduced decay amplitude at any given time. Here we examine the decay of motor adaptation following the learning of novel environmental dynamics in order to carefully evaluate this hypothesis. To account for potential issues in previous work that supported the context-dependent decay hypothesis, we measured decay using a balanced and baseline-referenced experimental design that allowed for direct comparisons between analogous masked and unmasked context changes. Using both an unbiased variant of the previous decay onset analysis and a novel highly-powered group-level version of this analysis, we found no evidence for systematically delayed decay onset nor for the masked context change affecting decay amplitude or its onset time. We further show how previous estimates of decay onset latency can be substantially biased in the presence of noise, and even more so with correlated noise, explaining the discrepancy between the previous results and our findings. Our results suggest that the decay of motor memories is an intrinsic feature of error-based learning that does not depend on context change detection.     

Ketamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions

Delusions are the persistent and often bizarre beliefs that characterise psychosis. Previous studies have suggested that their emergence may be explained by disturbances in prediction error-dependent learning. Here we set up complementary studies in order to examine whether such a disturbance also modulates memory reconsolidation and hence explains their remarkable persistence. First, we quantified individual brain responses to prediction error in a causal learning task in 18 human subjects (8 female). Next, a placebo-controlled within-subjects study of the impact of ketamine was set up on the same individuals. We determined the influence of this NMDA receptor antagonist (previously shown to induce aberrant prediction error signal and lead to transient alterations in perception and belief) on the evolution of a fear memory over a 72 hour period: they initially underwent Pavlovian fear conditioning; 24 hours later, during ketamine or placebo administration, the conditioned stimulus (CS) was presented once, without reinforcement; memory strength was then tested again 24 hours later. Re-presentation of the CS under ketamine led to a stronger subsequent memory than under placebo. Moreover, the degree of strengthening correlated with individual vulnerability to ketamine''s psychotogenic effects and with prediction error brain signal. This finding was partially replicated in an independent sample with an appetitive learning procedure (in 8 human subjects, 4 female). These results suggest a link between altered prediction error, memory strength and psychosis. They point to a core disruption that may explain not only the emergence of delusional beliefs but also their persistence.     

Reconsolidation and the Dynamic Nature of Memory

Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Research on reconsolidation was revitalized only more than a decade ago with the demonstration of reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat) subserved by an identified brain circuit (basolateral amygdala). Since then, reconsolidation has been shown in many studies over a range of species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have also been identified. In this review, I will first define the evidence on which reconsolidation is based, and proceed to discuss some of the conceptual issues facing the field in determining when reconsolidation does and does not occur. Last, I will refer to the potential clinical implications of reconsolidation.Learning and memory are commonly depicted as going through a set of phases. There is the learning or encoding phase, in which information is acquired, by stabilization phase, in which specific mechanisms are engaged to stabilize initially unstable new information (referred to as synaptic consolidation) (Glickman 1961; McGaugh 1966), the “storage” or maintenance phase, during which other mechanisms are involved to maintain the memory, and the retrieval phase, in which specific mechanisms permit a memory to be retrieved (Miller and Springer 1973; Spear 1973). For a long time, from a neurobiological perspective, only acquisition and memory stabilization (Martin et al. 2000; Kandel 2001; Dudai 2004) were considered to be active phases, in the sense that neurons had to perform certain computations or synthesize new RNA and proteins for these phases of memory processing to be performed successfully. After acquisition and stabilization, all other phases were implicitly thought by many to be passive readout of changes in the circuits mediating the long-term memory (LTM). However, the picture has now changed and the maintenance of memory is portrayed as an active process. One of the reasons for this change is the demonstration that a consolidated LTM can become susceptible to disruption and restoration, a process termed “reconsolidation” (Spear 1973; Nader et al. 2000; Sara 2000). There are now detailed molecular and cellular models of this time-dependent active memory phase.This review will first describe the logic of the findings that brought the existence of the consolidation process to light. I will then describe how we concluded that a consolidated memory undergoes reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat). I will then refer to the range of species, tasks, and treatments in which reconsolidation have been reported. One aspect of reconsolidation that has attracted experimental attention involves the finding that there seem to be conditions that facilitate, inhibit, or even prevent reconsolidation from occurring. I present an approach that could help to identify such conditions. Last, I will discuss potential clinical implications of reconsolidation.     

Reconsolidation: the advantage of being refocused

Ample evidence suggests that upon their retrieval, items in long-term memory enter a transient special state, in which they might become prone to change. The process that generates this state is dubbed 'reconsolidation'. The dominant conceptual framework in this revitalized field of memory research focuses on whether reconsolidation resembles consolidation, which is the process that converts an unstable short-term memory trace into a more stable long-term trace. However, this emphasis on the comparison of reconsolidation to consolidation deserves reassessment. Instead, the phenomenon of reconsolidation, irrespective of its relevance to consolidation, provides a unique opportunity to tap into the molecular, cellular and circuit correlates of memory persistence and retrieval, of which we currently know only little.