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Two contrasting theories have been proposed to explain the mechanistic basis of short term memory. One theory posits that short term memory is represented by persistent neural activity supported by reverberating feedback networks. An alternate, more recent theory posits that short term memory can be supported by feedforward networks. While feedback driven memory can be implemented by well described mechanisms of synaptic plasticity, little is known of possible molecular and cellular mechanisms that can implement feedforward driven memory. Here we report such a mechanism in which the memory trace exists in the form of glutamate-bound but Mg(2+)-blocked NMDA receptors on the thin terminal dendrites of CA1 pyramidal neurons. Because glutamate dissociates from subsets of NMDA receptors very slowly, excitatory synaptic transmission can leave a silent residual trace that outlasts the electrical activity by hundreds of milliseconds. Read-out of the memory trace is possible if a critical level of these bound-but-blocked receptors accumulates on a dendritic branch that will allow these quasi-stable receptors to sustain a regenerative depolarization when triggered by an independent gating signal. This process is referred to here as dendritic hold and read (DHR). Because the read-out of the input is not dependent on repetition of the input and information flows in a single-pass manner, DHR can potentially support a feedforward memory architecture.
Ketamine, a non-competitive NMDA receptor antagonist, has been reported to mimic the cognitive symptoms of schizophrenia in animals. It has been reported to produce learning and memory deficits in rodents. However, there have limited number of reports that investigated the specific components of memory process that are affected with ketamine. In the present study, we investigated the effects of ketamine [8 and 20 mg/kg, intraperitoneally, (i.p.)] on storage and retrieval of information in rats using an object recognition test. We examined also whether a low dose range of the D1/D2 dopamine receptor agonist apomorphine (0.05 and 0.1 mg/kg, i.p.) would counteract the effects of ketamine. The results show that ketamine dose-dependently impaired storage of information while it did not affect rats' retrieval abilities. Administration of apomorphine reversed the ketamine-induced performance deficits in the ORT. The current findings show a differential modulation of post-training memory components (storage and retrieval of information) by ketamine and suggest a functional interaction between dopamine and NMDA receptors in the control of memory storage which may be of relevance to cognitive deficits a core feature of schizophrenia.
Inaccessibility of stored memory in ensemble cells through the forgetting process causes animals to be unable to respond to natural recalling cues. While accumulating evidence has demonstrated that reactivating memory-stored cells can switch cells from an inaccessible state to an accessible form and lead to recall of previously learned information, the underlying cellular and molecular mechanisms remain elusive. The current study used Drosophila as a model to demonstrate that the memory of one-trial aversive olfactory conditioning, although inaccessible within a few hours after learning, is stored in KCαβ and retrievable after mild retraining. One-trial aversive conditioning triggers protein synthesis to form a long-lasting cellular memory trace, approximately 20 days, via creb in KCαβ, and a transient cellular memory trace, approximately one day, via orb in MBON-α3. PPL1-α3 negatively regulates forgotten one-trial conditioning memory retrieval. The current study demonstrated that KCαβ, PPL1-α3, and MBON-α3 collaboratively regulate the formation of forgotten one-cycle aversive conditioning memory formation and retrieval.
Life science research now heavily relies on all sorts of databases for genome sequences, transcription, protein three-dimensional (3D) structures, protein-protein interactions, phenotypes and so forth. The knowledge accumulated by all the omics research is so vast that a computer-aided search of data is now a prerequisite for starting a new study. In addition, a combinatory search throughout these databases has a chance to extract new ideas and new hypotheses that can be examined by wet-lab experiments. By virtually integrating the related databases on the Internet, we have built a new web application that facilitates life science researchers for retrieving experts' knowledge stored in the databases and for building a new hypothesis of the research target. This web application, named VaProS, puts stress on the interconnection between the functional information of genome sequences and protein 3D structures, such as structural effect of the gene mutation. In this manuscript, we present the notion of VaProS, the databases and tools that can be accessed without any knowledge of database locations and data formats, and the power of search exemplified in quest of the molecular mechanisms of lysosomal storage disease. VaProS can be freely accessed at http://p4d-info.nig.ac.jp/vapros/ .
Biomedical literature retrieval is becoming increasingly complex, and there is a fundamental need for advanced information retrieval systems. Information Retrieval (IR) programs scour unstructured materials such as text documents in large reserves of data that are usually stored on computers. IR is related to the representation, storage, and organization of information items, as well as to access. In IR one of the main problems is to determine which documents are relevant and which are not to the user's needs. Under the current regime, users cannot precisely construct queries in an accurate way to retrieve particular pieces of data from large reserves of data. Basic information retrieval systems are producing low-quality search results. In our proposed system for this paper we present a new technique to refine Information Retrieval searches to better represent the user's information need in order to enhance the performance of information retrieval by using different query expansion techniques and apply a linear combinations between them, where the combinations was linearly between two expansion results at one time. Query expansions expand the search query, for example, by finding synonyms and reweighting original terms. They provide significantly more focused, particularized search results than do basic search queries.
Every month, numerous publications appear that include neuroanatomic volumetric observations. The current and past literature that includes volumetric measurements is vast, but variable with respect to specific species, structures, and subject characteristics (such as gender, age, pathology, etc.). In this report we introduce the Internet Brain Volume Database (IBVD), www.nitrc.org/projects/ibvd , a site devoted to facilitating access to and utilization of neuroanatomic volumetric observations as published in the literature. We review the design and functionality of the site. The IBVD is the first database dedicated to integrating, exposing and sharing brain volumetric observations across species and disease. It offers valuable functionality for quality assurance assessment of results as well as support for meta-analysis across large segments of the published literature that are obscured from traditional text-based search engines.
Mental schemas exert top-down control on information processing, for instance by facilitating the storage of schema-related information. However, given capacity-limits and competition in neural network processing, schemas may additionally exert their effects by suppressing information with low momentary relevance. In particular, when existing schemas suffice to guide goal-directed behavior, this may actually reduce encoding of the redundant sensory input, in favor of gaining efficiency in task performance. The present experiment set out to test this schema-induced shallow encoding hypothesis. Our approach involved a memory task in which faces had to be coupled to homes. For half of the faces the responses could be guided by a pre-learned schema, for the other half of the faces such a schema was not available. Memory storage was compared between schema-congruent and schema-incongruent items. To characterize putative schema effects, memory was assessed both with regard to visual details and contextual aspects of each item. The depth of encoding was also assessed through an objective neural measure: the parietal old/new ERP effect. This ERP effect, observed between 500-800 ms post-stimulus onset, is thought to reflect the extent of recollection: the retrieval of a vivid memory, including various contextual details from the learning episode. We found that schema-congruency induced substantial impairments in item memory and even larger ones in context memory. Furthermore, the parietal old/new ERP effect indicated higher recollection for the schema-incongruent than the schema-congruent memories. The combined findings indicate that, when goals can be achieved using existing schemas, this can hinder the in-depth processing of novel input, impairing the formation of perceptually detailed and contextually rich memory traces. Taking into account both current and previous findings, we suggest that schemas can both positively and negatively bias the processing of sensory input. An important determinant in this matter is likely related to momentary goals, such that mental schemas facilitate memory processing of goal-relevant input, but suppress processing of goal-irrelevant information.
The Catalog and Index of French-language Health Internet resources (CISMeF) is a quality-controlled health gateway, primarily for Web resources in French (n=89,751). Recently, we achieved a major improvement in the structure of the catalogue by setting-up multiple terminologies, based on twelve health terminologies available in French, to overcome the potential weakness of the MeSH thesaurus, which is the main and pivotal terminology we use for indexing and retrieval since 1995. The main aim of this study was to estimate the added-value of exploiting several terminologies and their semantic relationships to improve Web resource indexing and retrieval in CISMeF, in order to provide additional health resources which meet the users' expectations.
DNA is an emerging medium for digital data and its adoption can be accelerated by synthesis processes specialized for storage applications. Here, we describe a de novo enzymatic synthesis strategy designed for data storage which harnesses the template-independent polymerase terminal deoxynucleotidyl transferase (TdT) in kinetically controlled conditions. Information is stored in transitions between non-identical nucleotides of DNA strands. To produce strands representing user-defined content, nucleotide substrates are added iteratively, yielding short homopolymeric extensions whose lengths are controlled by apyrase-mediated substrate degradation. With this scheme, we synthesize DNA strands carrying 144 bits, including addressing, and demonstrate retrieval with streaming nanopore sequencing. We further devise a digital codec to reduce requirements for synthesis accuracy and sequencing coverage, and experimentally show robust data retrieval from imperfectly synthesized strands. This work provides distributive enzymatic synthesis and information-theoretic approaches to advance digital information storage in DNA.
Several findings indicate that practice in working memory tasks leads to signal decreases in task-relevant regions. However, the precise dynamics underlying these signal decreases and how they are correlated with improvements in behavioral performance are still matters of debate. We used functional magnetic resonance imaging (fMRI) to assess the cerebral correlates of the practice-related transition from controlled to automatic processing for the retrieval of information maintained in working memory storage. Exponential signal decreases and increases were modeled as covariates of interest. In addition, a bivariate regression analysis on the change in BOLD signal for two a priori hypothesized prefrontal regions (VLPFC, DLPFC) and the change in behavioral performance was conducted to examine the relationship between practice-related changes in cerebral activation and performance. We found exponential practice-related signal decreases mainly in the right superior frontal gyrus/DLPFC (BA 8/9/46), the middle frontal gyrus bilaterally (BA 10/11), the left precentral gyrus (BA 4/6) and the dorsal part of the right anterior cingulate cortex (BA 32). An exponential signal increase was detectable in the posterior cingulate cortex adjacent to the corpus callosum. In addition, there was a correlation between the practice-related change in BOLD signal in the DLPFC (BA 8/9) and the practice-related change in behavioral performance. These results suggest that the transition from controlled to automatic working memory processing is associated with exponential signal decreases in task-relevant regions. The temporal changes in brain activation patterns could be attributed to enhanced efficiency of information processing as a result of cognitive practice.
The Online Chemical Modeling Environment is a web-based platform that aims to automate and simplify the typical steps required for QSAR modeling. The platform consists of two major subsystems: the database of experimental measurements and the modeling framework. A user-contributed database contains a set of tools for easy input, search and modification of thousands of records. The OCHEM database is based on the wiki principle and focuses primarily on the quality and verifiability of the data. The database is tightly integrated with the modeling framework, which supports all the steps required to create a predictive model: data search, calculation and selection of a vast variety of molecular descriptors, application of machine learning methods, validation, analysis of the model and assessment of the applicability domain. As compared to other similar systems, OCHEM is not intended to re-implement the existing tools or models but rather to invite the original authors to contribute their results, make them publicly available, share them with other users and to become members of the growing research community. Our intention is to make OCHEM a widely used platform to perform the QSPR/QSAR studies online and share it with other users on the Web. The ultimate goal of OCHEM is collecting all possible chemoinformatics tools within one simple, reliable and user-friendly resource. The OCHEM is free for web users and it is available online at http://www.ochem.eu.
Associative learning and memory are essential to logical thinking and cognition. How the neurons are recruited as associative memory cells to encode multiple input signals for their associated storage and distinguishable retrieval remains unclear. We studied this issue in the barrel cortex by in vivo two-photon calcium imaging, electrophysiology, and neural tracing in our mouse model that the simultaneous whisker and olfaction stimulations led to odorant-induced whisker motion. After this cross-modal reflex arose, the barrel and piriform cortices connected. More than 40% of barrel cortical neurons became to encode odor signal alongside whisker signal. Some of these neurons expressed distinct activity patterns in response to acquired odor signal and innate whisker signal, and others encoded similar pattern in response to these signals. In the meantime, certain barrel cortical astrocytes encoded odorant and whisker signals. After associative learning, the neurons and astrocytes in the sensory cortices are able to store the newly learnt signal (cross-modal memory) besides the innate signal (native-modal memory). Such associative memory cells distinguish the differences of these signals by programming different codes and signify the historical associations of these signals by similar codes in information retrievals.
Spontaneous and radiation-induced mutants of soybean, despite loss of abundant seed proteins, have been reported to grow and reproduce normally without any apparent physiological abnormalities. Here, we report the development and characterization of a soybean line (BSH-2) that lacks several abundant seed storage proteins. One-dimensional and high-resolution two-dimensional gel electrophoresis revealed the absence of the α' and α subunits of β-conglycinin and G1, G2, G4, and G5 glycinin in the newly developed mutant line (BSH-2). Like our earlier developed soybean mutant line (BSH-3), the seeds of BSH-2 also accumulated high levels of free amino acids as compared with wild-type DN47 seeds. An examination of the germination rates revealed that both BSH-2 and BSH-3 had significantly lower germination rates compared with the parent line DN47. Two-dimensional gel electrophoresis analysis demonstrated that these mutants had slower rates of mobilization of seed storage proteins. The delayed mobilization of storage proteins in BSH-2 and BSH-3 seeds was also correlated with a delayed induction of proteolytic activity in the mutants when compared to DN47. Similarly, qRT-PCR analysis revealed distinct expression pattern of genes involved in proteolytic pathway in the mutants when compared to DN47. Transmission electron microscopy observation of soybean seeds at two germination stages revealed striking differences in the breakdown of protein storage vacuoles and lipid bodies in the mutants. Our study demonstrates that BSH-2 and BSH-3 are compromised in mobilization of storage reserves and the absence of abundant storage proteins may affect the seed germination efficiency and post-germinative seedling establishment.
Navigating toward a goal and mentally comparing distances and directions to landmarks are processes requiring reading information off the memorized representation of the environment, that is, the cognitive map. Brain structures in the medial temporal lobe, in particular, are known to be involved in the learning, storage, and retrieval of cognitive map information, which is generally assumed to be in allocentric form, whereby pure spatial relations (i.e., distance and direction) connect locations with each other. The authors recorded functional magnetic resonance imaging activity, while participants were submitted to a variant of a neuropsychological test (the Cognitive Map Reading Test; CMRT) originally developed to evaluate the performance of brain-lesioned patients and in which participants have to compare distances and directions in their mental map of their hometown. Our main results indicated posterior parahippocampal, but not hippocampal, activity, consistent with a task involving spatial memory of places learned a long time ago; left parietal and left frontal activity, consistent with the distributed processing of navigational representations; and, unexpectedly, cerebellar activity, possibly related to the role of the cerebellum in the processing of (here, imaginary) self-motion cues. In addition, direction, but not distance, comparisons elicited significant activation in the posterior parahippocampal gyrus.
The molecules and mechanisms that are involved in the acquisition, storage, and retrieval of memories in many organisms are unclear. To investigate these processes, we use the nematode worm Caenorhabditis elegans, which is attracted naïvely to the odorant benzaldehyde but learns to avoid it after paired exposure with starvation. Mutations in the receptor-like guanylate cyclase GCY-28 have previously been thought to result in a behavioral switch in the primary chemosensory neuron AWCON , from an attractive state to an aversive (already-learned) state. Here, we offer a different interpretation and show that GCY-28 functions in distinct neurons to modulate two independent processes: naïve attraction to AWCON -sensed odors in the AWCON neuron, and associative learning of benzaldehyde and starvation in the AIA interneurons. Consequently, mutants that lack gcy-28 do not approach AWCON -sensed odors and cannot associate benzaldehyde with starvation. We further show that this learning deficit lies in memory retrieval, not in its acquisition or storage, and that GCY-28 is required in AIA for sensory integration only when both AWC neurons (ON and OFF) are activated by chemical stimuli. Our results reveal a novel role of GCY-28 in the retrieval of associative memories and may have wide implications for the neural machineries of learning and memory in general.
The advent of high-throughput sequencing has enabled sequencing based measurements of cellular function, with an individual measurement potentially consisting of more than 108 reads. While tools are available for aligning sets of reads to genomes and interpreting the results, fewer tools have been developed to address the storage and retrieval requirements of large collections of aligned datasets. We present ReadDB, a network accessible column store database system for aligned high-throughput read datasets.
Energy storage ceramics is among the most discussed topics in the field of energy research. A bibliometric analysis was carried out to evaluate energy storage ceramic publications between 2000 and 2020, based on the Web of Science (WOS) databases. This paper presents a detailed overview of energy storage ceramics research from aspects of document types, paper citations, h-indices, publish time, publications, institutions, countries/regions, research areas, highly cited papers, and keywords. A total of 3177 publications were identified after retrieval in WOS. The results show that China takes the leading position in this research field, followed by the USA and India. Xi An Jiao Tong Univ has the most publications, with the highest h-index. J.W. Zhai is the most productive author in energy storage ceramics research. Ceramics International, Journal of Materials Science-Materials in Electronics, and the Journal of Alloys and Compounds are the most productive journals in this field, and materials science-multidisciplinary is the most frequently used subject category. Keywords, highly cited papers, and the analysis of popular papers indicate that, in recent years, lead-free ceramics are prevalent, and researchers focus on fields such as the microstructure, thin films, and phase transition of ceramics.
Memory is a cognitive concept and refers to the storage of information over a longer time period. It exists of a series of complementary processes; acquisition, consolidation, and retrieval. Each of these processes has its own partly unique neurobiological signature. Sleep deprivation is known to impair hippocampus-dependent long-term memories. Many studies have used extended periods of wakefulness, affecting all three memory processes, thereby making it unable to determine how each of the processes is affected by sleep loss, separately. Others have extensively examined the effects on memory consolidation, showing the detrimental effect of sleep deprivation during the consolidation process on memory formation. Few studies have investigated how memory acquisition and its retrieval are affected by sleep loss. In the present study, we therefore assessed in mice how sleep deprivation negatively impacts memory acquisition, consolidation, and retrieval, in the Object Location Memory task. Mice were sleep deprived for six hours at the beginning of the light phase using the gentle handling method, 1) directly preceding the learning trial (acquisition), 2) immediately after the learning trial (consolidation), or 3) directly preceding the test trial (retrieval). Memory was assessed at either a 24-h or 1-h interval. Using this approach, we show for the first time that six hours of sleep deprivation attenuates the acquisition, consolidation, and retrieval of object-location memories in mice.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.
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