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Concept: Memory consolidation

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It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video’s content. We argue that these representations combine both new episodic information and stored semantic knowledge (or “schemas”). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature.

Concepts: Memory, Cerebrum, Hippocampus, Episodic memory, Semantic memory, Cingulate cortex, Memory consolidation, Video clip

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Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory.

Concepts: Amygdala, Memory, Hippocampus, Long-term potentiation, Episodic memory, Amnesia, Semantic memory, Memory consolidation

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Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being “recontextualization,” or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate.

Concepts: Memory, Hippocampus, Episodic memory, Procedural memory, Amnesia, Semantic memory, Declarative memory, Memory consolidation

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Although disrupting the process of memory reconsolidation has a great potential for clinical practice, the fear-amnesic effects are typically demonstrated through Pavlovian conditioning. Given that older and stronger memories are generally more resistant to change, we tested whether disrupting reconsolidation would also diminish fear in individuals who had developed a persistent spider fear outside the laboratory.

Concepts: Psychology, Amygdala, Memory, Hippocampus, Behaviorism, Episodic memory, Amnesia, Memory consolidation

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Despite accumulating evidence for a reconsolidation process in animals, support in humans, especially for episodic memory, is limited. Using a within-subjects manipulation, we found that a single application of electroconvulsive therapy following memory reactivation in patients with unipolar depression disrupted reactivated, but not non-reactivated, memories for an emotional episode in a time-dependent manner. Our results provide evidence for reconsolidation of emotional episodic memories in humans.

Concepts: Memory, Hippocampus, Episodic memory, Procedural memory, Amnesia, Semantic memory, Declarative memory, Memory consolidation

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Background: Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the β-blocker propranolol to block the consolidation/ reconsolidation of emotional memories in healthy adults. Methods: Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model. Results: Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00). Limitations: Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results. Conclusion: Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations, such as patients with posttraumatic stress or other event-related disorders.

Concepts: Amygdala, Memory, Clinical research, Meta-analysis, Episodic memory, Emotion and memory, Random effects model, Memory consolidation

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Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process-the standard theory of memory consolidation-would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might alreadyab ovobe encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.

Concepts: Psychology, Amygdala, Neuroscience, Memory, Hippocampus, Episodic memory, Memory consolidation, Multiple trace theory

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The default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1-3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4, 5]-particularly in DMN regions [6-8]. Mechanistic support for the DMN’s role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples-both during sleep [9, 10] and awake deliberative periods [11-13]. Ripples are ideally suited for memory consolidation [14, 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16-19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20-22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24-26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs-like the DMN-unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics.

Concepts: Cerebral cortex, Memory, Hippocampus, Schizophrenia, Episodic memory, Amnesia, Semantic memory, Memory consolidation

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Our own experiences, as well as the findings of many studies, suggest that emotionally arousing experiences can create lasting memories. This autobiographical article provides a brief summary of the author’s research investigating neurobiological systems responsible for the influence of emotional arousal on the consolidation of lasting memories. The research began with the finding that stimulant drugs enhanced memory in rats when administered shortly after training. Those findings suggested the possibility that endogenous systems activated by arousal might influence neural processes underlying memory consolidation. Subsequent findings that adrenal stress hormones activated by learning experiences enhance memory consolidation provided strong evidence supporting this hypothesis. Other findings suggest that the enhancement is induced by stress hormone activation of the amygdala. The findings also suggest that the basolateral amygdala modulates memory consolidation via its projections to brain regions involved in processing different aspects and forms of memory. This emotional-arousal-activated neurobiological system thus seems to play an important adaptive role in insuring that the strength of our memories will reflect their emotional significance.

Concepts: Nervous system, Psychology, Amygdala, Sleep, Neuroscience, Memory, Norepinephrine, Memory consolidation

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Curcumin, a yellow-pigment compound found in the popular Indian spice turmeric (Curcuma longa), has been extensively investigated for its anti-inflammatory, chemopreventative and antidepressant properties.Here, we examined the efficacy of dietary curcumin at impairing the consolidation and reconsolidation of a Pavlovian fear memory, a widely studied animal model of traumatic memory formation in post-traumatic stress disorder (PTSD).We show that a diet enriched with 1.5% curcumin preventsthe training-related elevation in the expression of the immediate early genes (IEGs) Arc/Arg3.1 and Egr-1 in the lateral amygdala (LA)and impairs the'consolidation' of an auditory Pavlovian fear memory; short-term memory (STM) is intact, while long-term memory (LTM) is significantly impaired. Next, we show that dietary curcuminimpairs the ‘reconsolidation’ of a recently formed auditory Pavlovian fear memory; fear memory retrieval (reactivation)and post-reactivation (PR)-STM are intact, while PR-LTM is significantly impaired. Additional experiments revealed that dietary curcumin is also effective at impairing the reconsolidation of an older, well-consolidated fear memory. Further, we observed that fear memories that fail to reconsolidate under the influence of dietary curcumin are impaired in an enduring manner; unlike extinguished fear memories they are not subject to reinstatement or renewal. Collectively, our findings indicate that a diet enriched with curcumin is capable of impairing fear memory consolidation and reconsolidation processes, findings which may have important clinical implications for the treatment of disorders such as PTSD that are characterized by unusually strong and persistently reactivated fear memories.Neuropsychopharmacology accepted article preview online, 28 November 2014. doi:10.1038/npp.2014.315.

Concepts: Alzheimer's disease, Amygdala, Memory, Psychological trauma, Episodic memory, Memory consolidation, Turmeric, Spice