Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference

Mounting behavioral evidence in humans supports the claim that sleep leads to improvements in recently acquired, nondeclarative memories. Examples include motor-sequence learning; visual-discrimination learning; and perceptual learning of a synthetic language. In contrast, there are limited human data supporting a benefit of sleep for declarative (hippocampus-mediated) memory in humans (for review, see). This is particularly surprising given that animal models (e.g.,) and neuroimaging studies (e.g.,) predict that sleep facilitates hippocampus-based memory consolidation. We hypothesized that we could unmask the benefits of sleep by challenging the declarative memory system with competing information (interference). This is the first study to demonstrate that sleep protects declarative memories from subsequent associative interference, and it has important implications for understanding the neurobiology of memory consolidation.     

Updating memories of unwanted emotions during human sleep

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Emotional memory: selective enhancement by sleep

Never go to sleep on an argument: an old wives' tale or a scientifically proven technique for controlling the memories you store? Recent findings show that sleep selectively enhances emotional memories, creating a long-lasting and potentially traumatic representation of distressing experiences.     

Hidden memories: frontline memory T cells and early pathogen interception

Immunologic memory reflects the ability of a host to more effectively respond to a re-encounter with a particular pathogen than the first encounter, and when a vaccine mimics the first encounter, comprises the basis of vaccine efficacy. For T cells, memory is often equated with the anamnestic response, the ability of secondary lymphoid tissue-based (central) memory T cells to respond to pathogen exposure with a more rapid and higher magnitude production and infection-site delivery of pathogen-specific effector cells than observed in naive hosts. However, increasing evidence supports a fundamentally different kind of T cell memory in which differentiated, long-lived effector memory T cells, prepositioned in sites of potential pathogen invasion or rapidly mobilized to such sites from blood and marginated pools, intercept and potentially control/eliminate pathogen within hours of infection. In this article, we review the evidence for this "hidden" T cell memory and its implication for vaccine development.     

Managing memories in post-war Sarajevo: individuals, bad memories, and new wars

In the wake of the 1992-5 war in Bosnia a number of anthropologists have written about the role of memory in creating and sustaining hostility in the region. One trend focuses on the authenticity and power of personal memories of Second World War violence and on the possibility of transmitting such memories down the generations to the 1990s. Another focuses less on memory as a phenomenon which determines human action than on the 'politics of memory': the political dynamics which play on and channel individuals' memories. In this article I use the example of three Sarajevo Bosniacs whom I have known since the pre-war 1980s in order to propose the merit of a third, additional, focus on the individual as an active manager of his or her own memories. I briefly consider whether work by Maurice Bloch on the nature of semantic and of autobiographic memory supports a strong version of the first interpretative trend, or whether, as I suggest, the conclusions of this work instead leave room for individual memory management and for change down the generations.     

Mesmerizing memories: brain substrates of episodic memory suppression in posthypnotic amnesia

Two groups of participants, one susceptible to posthypnotic amnesia (PHA) and the other not, viewed a movie. A week later, they underwent hypnosis in the fMRI scanner and received a suggestion to forget the movie details after hypnosis until receiving a reversal cue. The participants were tested twice for memory for the movie and for the context in which it was shown, under the posthypnotic suggestion and after its reversal, while their brain was scanned. The PHA group showed reduced memory for movie but not for context while under suggestion. Activity in occipital, temporal, and prefrontal areas differed among the groups, and, in the PHA group, between suggestion and reversal conditions. We propose that whereas some of these regions subserve retrieval of long-term episodic memory, others are involved in inhibiting retrieval, possibly already in a preretrieval monitoring stage. Similar mechanisms may also underlie other forms of functional amnesia.     

Cholesterol depletion induced by RNA interference targeting DHCR24 protects cells from liposome-induced cytotoxicity

Abstract

Existing evidence has demonstrated liposomes as the gene transporter induce the cytotoxicity during the transfection process through several known pathways. In the present study, we investigated the possibility of siRNAs targeting 3-β-hydroxysterol △-24-reductase (DHCR24), which encodes an enzyme catalyzing the last step of cholesterol biosynthesis, to suppress the liposome cytotoxicity induced by lipid-based transfection reagent in the neuroblastoma cell line N2A. We found that the siRNAs targeting DHCR24 mRNA protect cells from the liposome-induced cell death, probably through the effect of siDHCR24s on the reduction of the cellular cholesterol and decrease in the generation of reactive oxygen species (ROS). This suggests that siRNAs targeting DHCR24 or other methods that reduce the intracellular cholesterol levels might be a good strategy for avoiding the cytotoxicity of liposomes, without impairing its efficiency of gene-delivering.     

Active reversal of motor memories reveals rules governing memory encoding

Learning systems must be able to store memories reliably, yet be able to modify them when new learning is required. At the mechanistic level, new learning may either reverse the cellular events mediating the storage of old memories or mask the old memories with additional cellular changes that preserve the old cellular events in a latent form. Behavioral evidence about whether reversal or masking occurs in a particular circuit can constrain the cellular mechanisms used to store memories. Here we examine these constraints for a simple cerebellum-dependent learning task, motor learning in the vestibulo-ocular reflex (VOR). Learning can change the amplitude of the VOR in two opposite directions. Contrary to previous models about memory encoding by the cerebellum, our results indicate that these behavioral changes are implemented by different plasticity mechanisms, which reverse each other with unequal efficacy.     

Explicit and implicit memory during sleep

Sleep and Biological Rhythms - The purpose of this study was to indicate the changes in the implicit and explicit memory under awake and sleep conditions by using a battery that can measure...     

Mechanisms of interference in vibrotactile working memory

In previous studies of interference in vibrotactile working memory, subjects were presented with an interfering distractor stimulus during the delay period between the target and probe stimuli in a delayed match-to-sample task. The accuracy of same/different decisions indicated feature overwriting was the mechanism of interference. However, the distractor was presented late in the delay period, and the distractor may have interfered with the decision-making process, rather than the maintenance of stored information. The present study varies the timing of distractor onset, (either early, in the middle, or late in the delay period), and demonstrates both overwriting and non-overwriting forms of interference.     

Visual working memory capacity and proactive interference

Background

Visual working memory capacity is extremely limited and appears to be relatively immune to practice effects or the use of explicit strategies. The recent discovery that visual working memory tasks, like verbal working memory tasks, are subject to proactive interference, coupled with the fact that typical visual working memory tasks are particularly conducive to proactive interference, suggests that visual working memory capacity may be systematically under-estimated.

Methodology/Principal Findings

Working memory capacity was probed behaviorally in adult humans both in laboratory settings and via the Internet. Several experiments show that although the effect of proactive interference on visual working memory is significant and can last over several trials, it only changes the capacity estimate by about 15%.

Conclusions/Significance

This study further confirms the sharp limitations on visual working memory capacity, both in absolute terms and relative to verbal working memory. It is suggested that future research take these limitations into account in understanding differences across a variety of tasks between human adults, prelinguistic infants and nonlinguistic animals.     

Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells

Parp-1 and Parp-2 are activated by DNA breaks and have been implicated in the repair of DNA single-strand breaks (SSB). Their involvement in double-strand break (DSB) repair mediated by homologous recombination (HR) or nonhomologous end joining (NHEJ) remains unclear. We addressed this question using chicken DT40 cells, which have the advantage of carrying only a PARP-1 gene but not a PARP-2 gene. We found that PARP-1(-/-) DT40 mutants show reduced levels of HR and are sensitive to various DSB-inducing genotoxic agents. Surprisingly, this phenotype was strictly dependent on the presence of Ku, a DSB-binding factor that mediates NHEJ. PARP-1/KU70 double mutants were proficient in the execution of HR and displayed elevated resistance to DSB-inducing drugs. Moreover, we found deletion of Ligase IV, another NHEJ gene, suppressed the camptothecin of PARP-1(-/-) cells. Our results suggest a new critical function for Parp in minimizing the suppressive effects of Ku and the NHEJ pathway on HR.     

Thermoregulatory model of sleep control: losing the heat memory

Thermoregulatory mechanisms were hypothesized to provide primary control of non-rapid-eye-movement sleep (NREM). On the basis of this hypothesis, we incorporated the thermoregulatory feedback loops mediated by the "heat memory," heat load, and loss processes associated with sleep-wake cycles, which were modulated by two circadian oscillators. In addition, hypnogenic warm-sensitive neurons (HWSNs) were assumed to integrate thermoregulation and NREM control. The heat memory described above could be mediated by some sleep-promoting substances. In this paper, considering the possible carrier of the heat memory, its losing process is newly included in the model. The newly developed model can generate the appropriate features of human sleep-wake patterns. One of the special features of the model is to generate the bimodal distribution of the sleepiness. This bimodality becomes distinct, as the losing rate of the heat memory decreases or the amplitude of the Y oscillator increases. The theoretical analysis shows the losing rate of the heat memory control's rapidity of model response to a thermal perturbation, which is confirmed by simulating the responses with various losing rates to transient heat loads ("heat load pulse"). The sleepiness exhibits large responses to the heat load pulses applied in the early and late phases of wake period, while the response is significantly reduced to the pulse applied in the supposed wake-maintenance zone. This bimodality of the response appears to reflect the sensitivity of the HWSNs. In addition, the early pulse raises the immediate sleepiness rather than the nocturnal sleepiness, while the heat load pulse applied in the later phase of waking period significantly raises the sleepiness during a nocturnal sleep. In simulations of sleep deprivation, the discontinuous relationship between recovery sleep length and deprivation time is reproduced, where the critical sleep deprivation time at which the recovery sleep length jumps is extended as the losing rate increases. This is possibly due to the dissipation of the heat memory accumulated by the sleep deprivation. The simulation results here qualitatively reproduce the experimental observations or predict the intriguing phenomena of human circadian rhythms. Therefore, our model could provide a novel framework for investigating the relationship between thermoregulation and sleep control processes.     

Sleep improves memory: the effect of sleep on long term memory in early adolescence

Sleep plays an important role in the consolidation of memory. This has been most clearly shown in adults for procedural memory (i.e. skills and procedures) and declarative memory (e.g. recall of facts). The effects of sleep and memory are relatively unstudied in adolescents. Declarative memory is important in school performance and consequent social functioning in adolescents. This is the first study to specifically examine the effects of normal sleep on auditory declarative memory in an early adolescent sample. Given that the majority of adolescents do not obtain the recommended amount of sleep, it is critical to study the cognitive effects of normal sleep. Forty male and female normal, healthy adolescents between the ages of ten and fourteen years old were randomly assigned to sleep and no sleep conditions. Subjects were trained on a paired-associate declarative memory task and a control working memory task at 9am, and tested at night (12 hours later) without sleep. The same number of subjects was trained at 9pm and tested 9am following sleep. An increase of 20.6% in declarative memory, as measured by the number correct in a paired-associate test, following sleep was observed compared to the group which was tested at the same time interval without sleep (p<0.03). The performance on the control working memory task that involved encoding and memoranda manipulation was not affected by time of day or relationship to sleep. Declarative memory is significantly improved by sleep in a sample of normal adolescents.     

Episodic memory: new insights from the study of semantic dementia.

The study of patients with semantic dementia, the temporal variant of frontotemporal dementia, has provided new insights into the interaction between episodic and semantic memory, and the different roles played by various structures in the temporal lobe. Recent findings indicate that the syndrome of semantic dementia can inform us about the organisation of long-term memory and the relationship between semantic memory and other cognitive systems.