Synaptic protein degradation underlies destabilization of retrieved fear memory

Reactivated memory undergoes a rebuilding process that depends on de novo protein synthesis. This suggests that retrieval is dynamic and serves to incorporate new information into preexisting memories. However, little is known about whether or not protein degradation is involved in the reorganization of retrieved memory. We found that postsynaptic proteins were degraded in the hippocampus by polyubiquitination after retrieval of contextual fear memory. Moreover, the infusion of proteasome inhibitor into the CA1 region immediately after retrieval prevented anisomycin-induced memory impairment, as well as the extinction of fear memory. This suggests that ubiquitin- and proteasome-dependent protein degradation underlies destabilization processes after fear memory retrieval. It also provides strong evidence for the existence of reorganization processes whereby preexisting memory is disrupted by protein degradation, and updated memory is reconsolidated by protein synthesis.     

Memory's penumbra: episodic memory decisions induce lingering mnemonic biases

How do we decide if the people we meet and the things we see are familiar or new? If something is new, we need to encode it as a memory distinct from already stored episodes, using a process known as pattern separation. If familiar, it can be used to reactivate a previously stored memory, by a process known as pattern completion. To orchestrate these conflicting processes, current models propose that the episodic memory system uses environmental cues to establish processing biases that favor either pattern separation during encoding or pattern completion during retrieval. To assess this theory, we measured how people's memory formation and decisions are influenced by their recent engagement in episodic encoding and retrieval. We found that the recent encoding of novel objects improved subsequent identification of subtle changes, a task thought to rely on pattern separation. Conversely, recent retrieval of old objects increased the subsequent integration of stored information into new memories, a process thought to rely on pattern completion. These experiments provide behavioral evidence that episodic encoding and retrieval evoke lingering biases that influence subsequent mnemonic processing.     

正确认识年龄损害记忆——动物学研究

年龄相关性学习记忆能力减退是从人到啮齿类动物的常见现象.但因受到支持的记忆系统不同,各种类型的记忆形式受到年龄影响各不相同.并非所有形式的记忆都受损.受损的记忆消失也并非同时出现,且受损程度不同,以空间性记忆受损最早最重.衰老过程中,不同形式的记忆可能此消彼长,有些形式的记忆甚至可能增强.因此,在研究年龄相关性学习记忆能力减退时最好使用多个任务进行记忆评估.     

Memory in mice analyzed with antibiotics. Antibiotics are useful to study stages of memory and to indicate molecular events which sustain memory

It is apparent that antibiotics are useful in differentiating different stages in the formation of memory. Puromycin gave the first indication that very early memory can be established and survive, for a short period at least, in spite of inhibition of protein synthesis (12). Injection of actinomycin D indicates that RNA synthesis is not essential during this early stage (13). The duration of this early period seems to vary with the inhibiting agent; with puromycin memory was notably degraded in less than an hour, but with actinomycin D or with acetoxycycloheximide it persisted for several hours or more. The fixation or consolidation of memory involves whatever processes give permanence to memory. These processes are disrupted when electroconvulsive shock is administered shortly after a learning experience, presumably because of the interference with organized patterns of neuronal electrical activity. Memory acquired in the presence of antibiotics appears to proceed to a stage beyond that based purely on electrical activity because the memory persists beyond the period usually reported as sensitive to electroconvulsive shock. Further work should show whether this stage is truly insensitive to electroconvulsive shock. Memory acquired in the presence of puromycin does not seem to achieve any durable consolidation. In contrast, memory acquired in the presence of or immediately before injection of acetoxycycloheximide does appear to initiate the later stages of consolidation, as permanent memory. reappears some days after the initial stages have become ineffective in controlling performance. Finally, puromycin has provided evidence of the enlarged area of the neocortex which participates as memory matures. Puromycin also indicates the time required for this maturation process. Since antibiotics have also been useful in studying learning and memory in goldfish (14), this approach seems to have general applicability in defining various stages in the process of memory formation. The initial purpose of these investigations was to determine the molecular basis of the "memory trace" This goal still remains distant, although there are some indications that protein synthesizing systems are involved. This objective, though of enormous interest, is to be regarded as only a necessary first step. Whether new proteins or some other molecules cause the changes in synapses thought to underlie memory, this knowledge of itself will contribute only a beginning to our understanding of the events which account for the functioning of the brain. A determination of the composition of computer components would provide very little information towards unraveling their function. As the experiments proceeded, however, information of a more general nature was being obtained. The identification of different stages of consolidation show how injections of antibiotics can supplement electroconvulsive shock as a way of disrupting the establishment of memory and how it can supplement ablation in destroying memory already laid down in a permanent mode. Applied to larger animals the localization of various regions sensitive or insensitive to the action of the drugs should become more definitive. We hope that such experiments will contribute increasingly to the general problem of brain function.     

A neural mechanism for working and recognition memory in inferior temporal cortex

Inferior temporal (IT) cortex is critical for visual memory, but it is not known how IT neurons retain memories while new information is streaming into the visual system. Single neurons were therefore recorded from IT cortex of two rhesus monkeys performing tasks that required them to hold items in memory while concurrently viewing other items. The neuronal response to an incoming visual stimulus was attenuated if it matched a stimulus actively held in working memory, even when several other stimuli intervened. The neuronal response to novel stimuli declined as the stimuli became familiar to the animal. IT neurons appear to function as adaptive mnemonic "filters" that preferentially pass information about new, unexpected, or not recently seen stimuli.     

Three-dimensional optical storage memory

A novel three-dimensional (3-D) optical memory device is presented that allows fast random access of the information and extremely high bit densities. This device is based on two-photon writing, reading, and erasing of the information in a photochromic material embedded in a polymer matrix. Absorption and emission data show that two-photon writing and reading of information is feasible. The advantages and properties of such a 3-D optical memory are discussed.     

Effects of serotonin on memory impairments produced by ethanol

Subjects treated with low or high doses of ethanol demonstrated impaired memory, particularly in tests involving the recall of poorly learned information. Zimelidine, an inhibitor of serotonin reuptake, reversed this ethanol-induced impairment. The serotonin neurotransmitter system may mediate learning and memory in humans and may determine some of the effects of alcohol on higher mental functions.     

Schema-dependent gene activation and memory encoding in neocortex

When new learning occurs against the background of established prior knowledge, relevant new information can be assimilated into a schema and thereby expand the knowledge base. An animal model of this important component of memory consolidation reveals that systems memory consolidation can be very fast. In experiments with rats, we found that the hippocampal-dependent learning of new paired associates is associated with a striking up-regulation of immediate early genes in the prelimbic region of the medial prefrontal cortex, and that pharmacological interventions targeted at that area can prevent both new learning and the recall of remotely and even recently consolidated information. These findings challenge the concept of distinct fast (hippocampal) and slow (cortical) learning systems, and shed new light on the neural mechanisms of memory assimilation into schemas.     

Electronic spin storage in an electrically readable nuclear spin memory with a lifetime >100 seconds

Electron spins are strong candidates with which to implement spintronics because they are both mobile and able to be manipulated. The relatively short lifetimes of electron spins, however, present a problem for the long-term storage of spin information. We demonstrated an ensemble nuclear spin memory in phosphorous-doped silicon, which can be read out electrically and has a lifetime exceeding 100 seconds. The electronic spin information can be mapped onto and stored in the nuclear spin of the phosphorus donors, and the nuclear spins can then be repetitively read out electrically for time periods that exceed the electron spin lifetime. We discuss how this memory can be used in conjunction with other silicon spintronic devices.     

Forms of memory failure

Memory may fail in a variety of ways. Patients with Korsakoff's syndrome demonstrate global memory deficits similar to those seen in patients with early progressive dementia. Korsakoff's patients, however, may recall rules and principles for organizing information and can gain access to their previously acquired knowledge (semantic memory), whereas recent memory may be grossly impaired. In contrast, dementia patients may have little access to previously acquired knowledge and therefore have great difficulty in organizing and encoding ongoing events. These contrasting forms of memory failure have implications for understanding the structure and mechanisms of memory and learning, particularly the relationship between episodic and semantic memory, as well as the development of therapeutic strategies for cognitive impairments.     

Schemas and memory consolidation

Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed. New traces, trained for only one trial, then became assimilated and rapidly hippocampal-independent. Schemas also played a causal role in the creation of lasting associative memory representations during one-trial learning. The concept of neocortical schemas may unite psychological accounts of knowledge structures with neurobiological theories of systems memory consolidation.     

反复脑缺血再灌注对小鼠学习记忆和脑内氧化损伤的影响

目的建立血管性痴呆（VD）动物模型,并探讨反复脑缺血再灌注对小鼠认知障碍和脑组织氧化损伤的影响．方法健康的昆明小鼠30只,随机分为3组,即正常组、假手术组、模型组．采用清醒小鼠反复脑缺血再灌注手术方法,应用跳台法、避暗法、Morris水迷宫研究脑缺血再灌注对小鼠行为学的影响;通过HE、尼氏染色观察病理形态学变化;用生化分析方法检测脑组织中SOD活性、MDA的含量．结果与正常组比较,反复脑缺血再灌注能导致小鼠出现明显的学习记忆功能障碍,模型VD小鼠SOD的活性降低（P〈0．01）,MDA的含量增加（P〈0．01）．结论反复脑缺血再灌注能引起小鼠学习记忆功能障碍,这可能与脂质过氧化反应、自由基代谢紊乱有关．     

Glucocorticoids can induce PTSD-like memory impairments in mice

Posttraumatic stress disorder (PTSD) is characterized by a hypermnesia of the trauma and by a memory impairment that decreases the ability to restrict fear to the appropriate context. Infusion of glucocorticoids in the hippocampus after fear conditioning induces PTSD-like memory impairments and an altered pattern of neural activation in the hippocampal-amygdalar circuit. Mice become unable to identify the context as the correct predictor of the threat and show fear responses to a discrete cue not predicting the threat in normal conditions. These data demonstrate PTSD-like memory impairments in rodents and identify a potential pathophysiological mechanism of this condition.     

农业新闻数据源增量爬虫的研究

随着农业新闻数据日益膨胀,保证以农业为主题的增量爬虫成为爬取农业信息的相关手段,增量爬虫的原理可以依据农业新闻数据的更新爬取数据相关更新的内容,剔除出已经爬取的重复内容[[]]。文章结合农业新闻数据信息的特点,提出了一种适用于农业新闻信息的基于Redis的布隆过滤器的增量去重方法,摆脱超大的持久化文件撑爆内存的问题。通过实验证明随着抓取相关农业信息的增加,该方法在保证内存不被撑爆同时能有效提高增量爬取农业信息的效率,在增量信息爬取的过程中具有很好的应用价值[[]]。     

银杏叶提取物对去卵巢大鼠学习记忆功能的影响

利用水迷宫法研究了银杏叶提取物(EG b)对去卵巢大鼠学习记忆功能的影响,同时利用免疫组织化学SP法检测了大鼠海马中乙酰胆碱转移酶(ChAT)和神经元型一氧化氮合酶(NO S1)的表达情况。结果表明,去卵巢后大鼠学习记忆功能明显下降,海马中ChAT阳性神经元的表达明显减弱(P<0.05),NO S1阳性神经元(除CA 2区)的表达明显增强(P<0.01);EG b对雌激素缺乏所致的学习记忆功能下降具有明显的改善作用,其作用是通过增强海马中ChAT阳性神经元的表达和抑制NO S1阳性神经元的表达而实现的。     

Cognitive memory: cellular and network machineries and their top-down control

A brain-wide distributed network orchestrates cognitive memorizing and remembering of explicit memory (i.e., memory of facts and events). The network was initially identified in humans and is being systematically investigated in molecular/genetic, single-unit, lesion, and imaging studies in animals. The types of memory identified in humans are extended into animals as episodic-like (event) memory or semantic-like (fact) memory. The unique configurational association between environmental stimuli and behavioral context, which is likely the basis of episodic-like memory, depends on neural circuits in the medial temporal lobe, whereas memory traces representing repeated associations, which is likely the basis of semantic-like memory, are consolidated in the domain-specific regions in the temporal cortex. These regions are reactivated during remembering and contribute to the contents of a memory. Two types of retrieval signal reach the cortical representations. One runs from the frontal cortex for active (or effortful) retrieval (top-down signal), and the other spreads backward from the medial temporal lobe for automatic retrieval. By sending the top-down signal to the temporal cortex, frontal regions manipulate and organize to-be-remembered information, devise strategies for retrieval, and also monitor the outcome, with dissociated frontal regions making functionally separate contributions. The challenge is to understand the hierarchical interactions between these multiple cortical areas, not only with a correlational analysis but also with an interventional study demonstrating the causal necessity and the direction of the causality.     

Alzheimer's disease is a synaptic failure

In its earliest clinical phase, Alzheimer's disease characteristically produces a remarkably pure impairment of memory. Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid beta protein.     

CD-1小鼠海马H3K9三甲基化水平的年龄化改变 及其与认知功能改变的相关性研究

探讨年龄对CD-1小鼠海马组蛋白H3K9三甲基化(H3K9me3)含量的影响及其与空间学习记忆能力改变的相关性。结果发现,18月和12月龄鼠在放射状水迷宫中学习期和记忆期的潜伏期、错误数均高于6月龄鼠(P_s0.05);18月龄鼠学习期及记忆期的错误数还高于12月龄鼠(P_s0.05)。18月龄鼠海马DG和CA1区H3K9me3水平高于12月龄鼠(P_s0.05),12月龄鼠也高于6月龄鼠(P_s0.05)。DG和CA1区H3K9me3相对含量与学习期的潜伏期和错误数以及记忆期错误数呈正相关(P_s0.05),而CA3区H3K9me3相对含量与学习期和记忆期的错误数、潜伏期之间无明显相关性(P_s0.05)。以上结果提示,CD-1小鼠年龄相关空间学习记忆损害可能与海马组蛋白H3K9me3升高有关。     

Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells

The immune response is initiated in organized lymphoid tissues where antigen-loaded dendritic cells (DCs) encounter antigen-specific T cells. DCs function as packets of information that must be decoded by the T cell before an appropriate immune response can be mounted. We discuss how the dynamics of DC-T cell encounter and the mechanism of T cell differentiation make the decoding of this information stochastic rather than determinate. This results in the generation of both terminally differentiated effector cells and intermediates that play distinctive roles in protection, immunoregulation, and immunological memory.