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《Current biology : CB》2021,31(24):5450-5461.e4
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Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory.  相似文献   

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How are memories stored and retrieved? It was one of the most discussed questions in the past century by neuroscientists. Leading studies of the period brought two different explanations to this question: The first statement considers memory as a physiological change in the brain and suggest that the retrieval of memory is only occurred by the same physiologic changes observed during the memory formation, while the second suggests that memory is a psychic mood stored in mind and the retrieval of memory is occurred by mystical energy fluctuations. Although the exact reason and the pathogenesis of Alzheimer's disease have not yet been fully understood, the approaches that centered the retrieval strategy of lost memory constitutes the basis of the treatment strategies in Alzheimer's disease today. The majority of treatment studies has based on the manipulation of the cholinergic system; however, although serotonin has mnemonic effects, its role in the pathogenesis of Alzheimer's disease has not been investigated as much as the cholinergic system. Here we show how serotonin affects the pathogenesis of Alzheimer's disease in a comprehensive perspective and we suggest that the optogenetics manipulation of serotonin nuclei retrieve the lost memory by closing the inward-rectifier potassium channel Kir2 on the memory engram cells. Also, we raise the possible effects of serotonin on the memory engram cells and the interactions between the amyloid-centric hypothesis of Alzheimer's disease and the memory engram hypothesis to explain the pathophysiology of memory loss in Alzheimer's disease.  相似文献   

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《Current biology : CB》2019,29(11):1885-1894.e4
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Memory, defined as the storage and use of learned information in the brain, is necessary to modulate behavior and critical for animals to adapt to their environments and survive. Despite being a cornerstone of brain function, questions surrounding the molecular and cellular mechanisms of how information is encoded, stored, and recalled remain largely unanswered. One widely held theory is that an engram is formed by a group of neurons that are active during learning, which undergoes biochemical and physical changes to store information in a stable state, and that are later reactivated during recall of the memory. In the past decade, the development of engram labeling methodologies has proven useful to investigate the biology of memory at the molecular and cellular levels. Engram technology allows the study of individual memories associated with particular experiences and their evolution over time, with enough experimental resolution to discriminate between different memory processes: learning (encoding), consolidation (the passage from short-term to long-term memories), and storage (the maintenance of memory in the brain). Here, we review the current understanding of memory formation at a molecular and cellular level by focusing on insights provided using engram technology.  相似文献   

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《Cell》2021,184(24):5902-5915.e17
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The synaptic plasticity and memory hypothesis asserts that activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the encoding and trace storage of the type of memory mediated by the brain area in which it is observed. Criteria for establishing the necessity and sufficiency of such plasticity in mediating trace storage have been identified and are here reviewed in relation to new work using some of the diverse techniques of contemporary neuroscience. Evidence derived using optical imaging, molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing the strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain.  相似文献   

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Dream thought is both impoverished and non-logical. While some inferential reasoning is present in dreaming, many illogicalities that would demand cognitive attention during waking go unnoticed during sleep. The physiological basis of this illogicality may include frontal lobe inactivation and amionergic demodulation. (PsycINFO Database Record (c) 2011 APA, all rights reserved)  相似文献   

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《Neuron》2023,111(11):1830-1845.e5
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《Neuron》2022,110(18):3036-3052.e5
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《Neuron》2020,105(6):1077-1093.e7
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《Neuron》2022,110(8):1416-1431.e13
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《Neuron》2022,110(17):2790-2801.e5
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Mammalian interphase chromosomes fold into a multitude of loops to fit the confines of cell nuclei, and looping is tightly linked to regulated function. Chromosome conformation capture (3C) technology has significantly advanced our understanding of this structure‐to‐function relationship. However, all 3C‐based methods rely on chemical cross‐linking to stabilize spatial interactions. This step remains a “black box” as regards the biases it may introduce, and some discrepancies between microscopy and 3C studies have now been reported. To address these concerns, we developed “i3C”, a novel approach for capturing spatial interactions without a need for cross‐linking. We apply i3C to intact nuclei of living cells and exploit native forces that stabilize chromatin folding. Using different cell types and loci, computational modeling, and a methylation‐based orthogonal validation method, “TALE‐iD”, we show that native interactions resemble cross‐linked ones, but display improved signal‐to‐noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions.  相似文献   

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The home range and ranging pattern of the slender loris (Loris tardigradus lydekkerianus) was studied for 21 months in a scrub jungle in Dindigul, Tamil Nadu, south India. Sixteen individuals were observed for a total of 2261 hours. Home ranges were measured for eight adult individuals and eight juvenile and subadult individuals. Males had significantly larger home ranges than the females, and home range size increased post-weaning. The ranging patterns involved minimal female intrasexual overlap, large male intrasexual overlap and large intersexual range overlap.  相似文献   

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