Memories aren't made of this: amnesia at the movies.
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ABSTRACT:
SUBMITTER: Baxendale S
PROVIDER: S-EPMC535990 | biostudies-literature | 2004 Dec
REPOSITORIES: biostudies-literature
Publications
Memories aren't made of this: amnesia at the movies.
BMJ (Clinical research ed.) 20041201 7480
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Project description:Research on memory reconsolidation has been booming in the last two decades, with numerous high-impact publications reporting promising amnestic interventions in rodents and humans. However, our own recently-published failed replication attempts of reactivation-dependent amnesia for fear memories in rats suggest that such amnestic effects are not always readily found and that they depend on subtle and possibly uncontrollable parameters. The discrepancy between our observations and published studies in rodents suggests that the literature in this field might be biased. The aim of the current study was to gauge the presence of publication bias in a well-delineated part of the reconsolidation literature. To this end, we performed a systematic review of the literature on reactivation-dependent amnesia for contextual fear memories in rodents, followed by a statistical assessment of publication bias in this sample. In addition, relevant researchers were contacted for unpublished results, which were included in the current analyses. The obtained results support the presence of publication bias, suggesting that the literature provides an overly optimistic overall estimate of the size and reproducibility of amnestic effects. Reactivation-dependent amnesia for contextual fear memories in rodents is thus less robust than what is projected by the literature. The moderate success of clinical studies may be in line with this conclusion, rather than reflecting translational issues. For the field to evolve, replication and non-biased publication of obtained results are essential. A set of tools that can create opportunities to increase transparency, reproducibility and credibility of research findings is provided.
| S-EPMC7877470 | biostudies-literature
Project description:BackgroundLong-term memory formation is generally assumed to involve the permanent storage of recently acquired memories, making them relatively insensitive to disruption, a process referred to as memory consolidation. However, when retrieved under specific circumstances, consolidated fear memories are thought to return to a labile state, thereby opening a window for modification (e.g., attenuation) of the memory. Several interventions during a critical time frame after this destabilization seem to be able to alter the retrieved memory, for example by pharmacologically interfering with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol). Here, we find that, contrary to expectations, systemic pharmacological manipulations in auditory fear-conditioned rats do not lead to drug-induced post-retrieval amnesia.ResultsIn a series of well-powered auditory fear conditioning experiments (four with propranolol, 10 mg/kg, two with rapamycin, 20-40 mg/kg, one with anisomycin, 150 mg/kg and cycloheximide, 1.5 mg/kg), we found no evidence for reduced cued fear memory expression during a drug-free test in adult male Sprague-Dawley rats that had previously received a systemic drug injection upon retrieval of the tone fear memory. All experiments used standard fear conditioning and reactivation procedures with freezing as the behavioral read-out (conceptual or exact replications of published reports) and common pharmacological agents. Additional tests confirmed that the applied drug doses and administration routes were effective in inducing their conventional effects on expression of fear (propranolol, acutely), body weight (rapamycin, anisomycin, cycloheximide), and consolidation of extinction memories (cycloheximide).ConclusionsIn contrast with previously published studies, we did not find evidence for drug-induced post-retrieval amnesia, underlining that this effect, as well as its clinical applicability, may be considerably more constrained and less readily reproduced than what the current literature would suggest.
| S-EPMC7836479 | biostudies-literature
Project description:Macroevolutionary consequences of competition among large clades have long been sought in patterns of lineage diversification. However, mechanistically clear examples of such effects remain elusive. Here, we postulated that the limited phenotypic diversity and insular gigantism in lagomorphs could be explained at least in part by an evolutionary constraint placed on them by potentially competing ungulate-type herbivores (UTHs). Our analyses yielded three independent lines of evidence supporting this hypothesis: (1) the minimum UTH body mass is the most influential predictor of the maximum lagomorph body mass in modern ecoregions; (2) the scaling patterns of local-population energy use suggest universal competitive disadvantage of lagomorphs weighing over approximately 6.3 kg against artiodactyls, closely matching their observed upper size limit in continental settings; and (3) the trajectory of maximum lagomorph body mass in North America from the late Eocene to the Pleistocene (37.5-1.5 million years ago) was best modeled by the body mass ceiling placed by the smallest contemporary perissodactyl or artiodactyl. Body size evolution in lagomorphs has likely been regulated by the forces of competition within the clade, increased predation in open habitats, and importantly, competition from other ungulate-type herbivores. Our findings suggest conditionally-coupled dynamics of phenotypic boundaries among multiple clades within an adaptive zone, and highlight the synergy of biotic and abiotic drivers of diversity.
| S-EPMC8252017 | biostudies-literature
Project description:Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma.
| S-EPMC4796356 | biostudies-literature
Project description:BackgroundThe success of AlphaFold2 in reliable protein three-dimensional (3D) structure prediction, assists the move of structural biology toward studies of protein dynamics and mutational impact on structure and function. This transition needs tools that qualitatively assess alternative 3D conformations.ResultsWe introduce MutAmore, a bioinformatics tool that renders individual images of protein 3D structures for, e.g., sequence mutations into a visually intuitive movie format. MutAmore streamlines a pipeline casting single amino-acid variations (SAVs) into a dynamic 3D mutation movie providing a qualitative perspective on the mutational landscape of a protein. By default, the tool first generates all possible variants of the sequence reachable through SAVs (L*19 for proteins with L residues). Next, it predicts the structural conformation for all L*19 variants using state-of-the-art models. Finally, it visualizes the mutation matrix and produces a color-coded 3D animation. Alternatively, users can input other types of variants, e.g., from experimental structures.ConclusionMutAmore samples alternative protein configurations to study the dynamical space accessible from SAVs in the post-AlphaFold2 era of structural biology. As the field shifts towards the exploration of alternative conformations of proteins, MutAmore aids in the understanding of the structural impact of mutations by providing a flexible pipeline for the generation of protein mutation movies using current and future structure prediction models.
| S-EPMC10714560 | biostudies-literature
Project description:Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed ?1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.
| S-EPMC3970513 | biostudies-literature
Project description:Seizures cause retrograde amnesia, but underlying mechanisms are poorly understood. We tested whether seizure activated neuronal circuits overlap with spatial memory engram and whether seizures saturate LTP in engram cells. A seizure caused retrograde amnesia for spatial memory task. Spatial learning and a seizure caused cFos expression and synaptic plasticity overlapping set of neurons in the CA1 of the hippocampus. Recordings from learning-labeled CA1 pyramidal neurons showed potentiated synapses. Seizure-tagged neurons were also more excitable with larger rectifying excitatory postsynaptic currents than surrounding unlabeled neurons. These neurons had enlarged dendritic spines and saturated LTP. A seizure immediately after learning, reset the memory engram. Seizures cause retrograde amnesia through shared ensembles and mechanisms.
| S-EPMC8026600 | biostudies-literature
Project description:Recent advances in microscopy, computing power and image processing have enabled the analysis of ever larger datasets of movies of microorganisms to study their behaviour. However, techniques for analysing the dynamics of individual cells from such datasets are not yet widely available in the public domain. We recently demonstrated significant phenotypic heterogeneity in the adhesion of Escherichia coli bacteria to glass surfaces using a new method for the high-throughput analysis of video microscopy data. Here, we present an in-depth analysis of this method and its limitations, and make public our algorithms for following the positions and orientations of individual rod-shaped bacteria from time-series of 2D images to reconstruct their trajectories and characterise their dynamics. We demonstrate in detail how to use these algorithms to identify different types of adhesive dynamics within a clonal population of bacteria sedimenting onto a surface. The effects of measurement errors in cell positions and of limited trajectory durations on our results are discussed.
| S-EPMC6553751 | biostudies-literature
Project description:Despite replicated evidence for working memory deficits in youth with ADHD, no study has comprehensively assessed all three primary 'working' subcomponents of the working memory system in these children. Children ages 8-13 with (n = 45) and without (n = 41) ADHD (40% female; Mage = 10.5; 65% Caucasian/Non-Hispanic) completed a counterbalanced battery of nine tasks (three per construct) assessing working memory reordering (maintaining and rearranging information in mind), updating (active monitoring of incoming information and replacing outdated with relevant information), and dual-processing (maintaining information in mind while performing a secondary task). Detailed analytic plans were preregistered. Bayesian t-tests indicated that, at the group level, children with ADHD exhibited significant impairments in working memory reordering (BF10 = 4.64 × 105; d = 1.34) and updating (BF10 = 9.49; d = 0.64), but not dual-processing (BF01 = 1.33; d = 0.37). Overall, 67%-71% of youth with ADHD exhibited impairment in at least one central executive working memory domain. Reordering showed the most ADHD-related impairment, with 75% classified as below average or impaired, and none demonstrating strengths. The majority of children with ADHD (52%-57%) demonstrated average or better abilities in the remaining two domains, with a notable minority demonstrating strengths in updating (8%) and dual-processing (20%). Notably, impairments in domain-general central executive working memory, rather than individual subcomponents, predicted ADHD severity, suggesting that common rather than specific working memory mechanisms may be central to understanding ADHD symptoms. These impairment estimates extend prior work by providing initial evidence that children with ADHD not only exhibit heterogeneous profiles across cognitive domains but also exhibit significant heterogeneity within subcomponents of key cognitive processes.
| S-EPMC7192792 | biostudies-literature
Project description:Selective amnesia for previously established memories can be induced by administering drugs that impair protein synthesis shortly after memory reactivation. Competing theoretical accounts attribute this selective post-retrieval amnesia to drug-induced engram degradation (reconsolidation blockade) or to incorporation of sensory features of the reactivation experience into the memory representation, hampering later retrieval in a drug-free state (memory integration). Here we present evidence that critically challenges both accounts. In contextual fear conditioning in rats, we find that amnesia induced by administration of midazolam (MDZ) after reexposure to the training context A generalizes readily to a similar context B. Amnesia is also observed when animals are exposed to the similar context B prior to MDZ administration and later tested for fear to context B but recovers when instead testing for fear to the original training context A or an equally similar but novel context C. Next to their theoretical implications for the nature of forgetting, our findings raise important questions about the viability of reconsolidation-based interventions for the treatment of emotional disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
| S-EPMC7116269 | biostudies-literature