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Sample records for naive memory dependence

  1. Two separate defects affecting true naive or virtual memory T cell precursors combine to reduce naive T cell responses with aging.

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    Renkema, Kristin R; Li, Gang; Wu, Angela; Smithey, Megan J; Nikolich-Žugich, Janko

    2014-01-01

    Naive T cell responses are eroded with aging. We and others have recently shown that unimmunized old mice lose ≥ 70% of Ag-specific CD8 T cell precursors and that many of the remaining precursors acquire a virtual (central) memory (VM; CD44(hi)CD62L(hi)) phenotype. In this study, we demonstrate that unimmunized TCR transgenic (TCRTg) mice also undergo massive VM conversion with age, exhibiting rapid effector function upon both TCR and cytokine triggering. Age-related VM conversion in TCRTg mice directly depended on replacement of the original TCRTg specificity by endogenous TCRα rearrangements, indicating that TCR signals must be critical in VM conversion. Importantly, we found that VM conversion had adverse functional effects in both old wild-type and old TCRTg mice; that is, old VM, but not old true naive, T cells exhibited blunted TCR-mediated, but not IL-15-mediated, proliferation. This selective proliferative senescence correlated with increased apoptosis in old VM cells in response to peptide, but decreased apoptosis in response to homeostatic cytokines IL-7 and IL-15. Our results identify TCR as the key factor in differential maintenance and function of Ag-specific precursors in unimmunized mice with aging, and they demonstrate that two separate age-related defects--drastic reduction in true naive T cell precursors and impaired proliferative capacity of their VM cousins--combine to reduce naive T cell responses with aging.

  2. Decreased naive and increased memory CD4(+ T cells are associated with subclinical atherosclerosis: the multi-ethnic study of atherosclerosis.

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    Nels C Olson

    Full Text Available Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4(+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.We examined cross-sectional relationships of circulating CD4(+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA. Circulating CD4(+ naive cells were higher in women than men and decreased with age (all p-values <0.0001. European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005. Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05. Higher memory cells were associated with coronary artery calcification (CAC level in the overall population [β-Coefficient (95% confidence interval (CI  = 0.20 (0.03, 0.37]. Memory and naive (inversely cells were associated with common carotid artery intimal media thickness (CC IMT in European-Americans [memory: β =  0.02 (0.006, 0.04; naive: β = -0.02 (-0.004, -0.03].These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4(+ T cells, and with innate immunity (inflammation, in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate

  3. Dual role of miR-21 in CD4+ T-cells: activation-induced miR-21 supports survival of memory T-cells and regulates CCR7 expression in naive T-cells.

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    Katarzyna Smigielska-Czepiel

    Full Text Available Immune cell-type specific miRNA expression patterns have been described but the detailed role of single miRNAs in the function of T-cells remains largely unknown. We investigated the role of miR-21 in the function of primary human CD4+ T-cells. MiR-21 is substantially expressed in T-cells with a memory phenotype, and is robustly upregulated upon αCD3/CD28 activation of both naive and memory T-cells. By inhibiting the endogenous miR-21 function in activated naive and memory T-cells, we showed that miR-21 regulates fundamentally different aspects of T-cell biology, depending on the differentiation status of the T-cell. Stable inhibition of miR-21 function in activated memory T-cells led to growth disadvantage and apoptosis, indicating that the survival of memory T-cells depends on miR-21 function. In contrast, stable inhibition of miR-21 function in activated naive T-cells did not result in growth disadvantage, but led to a significant induction of CCR7 protein expression. Direct interaction between CCR7 and miR-21 was confirmed in a dual luciferase reporter assay. Our data provide evidence for a dual role of miR-21 in CD4+ T cells; Regulation of T-cell survival is confined to activated memory T-cells, while modulation of potential homing properties, through downregulation of CCR7 protein expression, is observed in activated naive T-cells.

  4. In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

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    Laksono, Brigitta M; Grosserichter-Wagener, Christina; de Vries, Rory D; Langeveld, Simone A G; Brem, Maarten D; van Dongen, Jacques J M; Katsikis, Peter D; Koopmans, Marion P G; van Zelm, Menno C; de Swart, Rik L

    2018-04-15

    Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T H ) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T H 1T H 17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the

  5. Impaired visual, working, and verbal memory in first-episode, drug-naive patients with major depressive disorder in a Chinese population.

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    Chen, Ce; Jiang, Wen-Hui; Wang, Wei; Ma, Xian-Cang; Li, Ye; Wu, Jin; Hashimoto, Kenji; Gao, Cheng-Ge

    2018-01-01

    Cognitive impairment has been observed in patients with major depressive disorder (MDD). However, it remains unclear whether the deficits in specific cognitive domains are present in first-episode, drug-naïve patients or medicated patients. In the present study, using the CogState battery (CSB) Chinese language version, we evaluated the visual, working, and verbal memory in first-episode drug-naive patients and medicated patients with MDD in a Chinese population. We measured the cognitive function in first-episode drug-naïve patients (n = 36), medicated MDD patients (n = 71), and age- and sex-matched healthy control subjects (n = 59) in a Chinese population. The CSB composite scores in both first-episode drug-naive patients and medicated patients were significantly poorer than those in the healthy control subjects. The CSB sub-scores, including visual, working, and verbal memory were also significantly poorer in both patient groups than those in the healthy control subjects. In contrast, processing speed, attention/vigilance, executive function, spatial working memory, and social cognition were no different from healthy controls, whereas the executive function was significantly better in the medicated patients than in the healthy control subjects and first-episode drug-naïve patients. These findings suggest an impairment in the visual, working, and verbal memory in first-episode, drug-naive MDD patients in a Chinese population.

  6. A Public Database of Memory and Naive B-Cell Receptor Sequences.

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    William S DeWitt

    Full Text Available The vast diversity of B-cell receptors (BCR and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

  7. A Public Database of Memory and Naive B-Cell Receptor Sequences.

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    DeWitt, William S; Lindau, Paul; Snyder, Thomas M; Sherwood, Anna M; Vignali, Marissa; Carlson, Christopher S; Greenberg, Philip D; Duerkopp, Natalie; Emerson, Ryan O; Robins, Harlan S

    2016-01-01

    The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

  8. The Ras GTPase-activating protein Rasal3 supports survival of naive T cells.

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    Ryunosuke Muro

    Full Text Available The Ras-mitogen-activated protein kinase (MAPK pathway is crucial for T cell receptor (TCR signaling in the development and function of T cells. The significance of various modulators of the Ras-MAPK pathway in T cells, however, remains to be fully understood. Ras-activating protein-like 3 (Rasal3 is an uncharacterized member of the SynGAP family that contains a conserved Ras GTPase-activating protein (GAP domain, and is predominantly expressed in the T cell lineage. In the current study, we investigated the function and physiological roles of Rasal3. Our results showed that Rasal3 possesses RasGAP activity, but not Rap1GAP activity, and represses TCR-stimulated ERK phosphorylation in a T cell line. In systemic Rasal3-deficient mice, T cell development in the thymus including positive selection, negative selection, and β-selection was unaffected. However, the number of naive, but not effector memory CD4 and CD8 T cell in the periphery was significantly reduced in Rasal3-deficient mice, and associated with a marked increase in apoptosis of these cells. Indeed, survival of Rasal3 deficient naive CD4 T cells in vivo by adoptive transfer was significantly impaired, whereas IL-7-dependent survival of naive CD4 T cells in vitro was unaltered. Collectively, Rasal3 is required for in vivo survival of peripheral naive T cells, contributing to the maintenance of optimal T cell numbers.

  9. Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps.

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    Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John; Vreugde, Sarah

    2018-01-01

    Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p Kruskal-Wallis test). Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP.

  10. The CD8+ memory T-cell state of readiness is actively maintained and reversible

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    Allam, Atef; Conze, Dietrich B.; Giardino Torchia, Maria Letizia; Munitic, Ivana; Yagita, Hideo; Sowell, Ryan T.; Marzo, Amanda L.

    2009-01-01

    The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cycle state and responded to stimulation like naive T cells, as assessed by proliferation, dependence upon costimulation, and interferon-γ production, without losing cell surface markers associated with memory. The memory state was maintained by signaling via members of the tumor necrosis factor receptor superfamily, CD27 and 4-1BB. Foxo1, a transcription factor involved in T-cell quiescence, was reduced in memory cells, and stimulation of naive CD8 cells via CD27 caused Foxo1 to be phosphorylated and emigrate from the nucleus in a phosphatidylinositol-3 kinase–dependent manner. Consistent with these results, maintenance of G1 in vivo was compromised in antigen-specific memory T cells in vesicular stomatitis virus-infected CD27-deficient mice. Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance. PMID:19617575

  11. Context-dependent memory: colour versus odour.

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    Pointer, S C; Bond, N W

    1998-06-01

    An olfactory stimulus and a visual stimulus were employed in a context-dependent memory study using a prose passage as the to-be-remembered item. Ninety-five university students (aged 17-35 years) learned the passage of prose in the presence of one of the stimuli and were then asked to recall the passage with the original context either reinstated or not reinstated. The results revealed a significant context-dependent memory effect for the olfactory cue but not for the visual cue. They demonstrate support for the effectiveness of odours as context cues and it is suggested that context-dependent memory processes may underlie the formation and retrieval of odour-evoked autobiographical memories.

  12. High-throughput gene expression profiling of memory differentiation in primary human T cells

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    Russell Kate

    2008-08-01

    Full Text Available Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1 the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2 a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

  13. Stress Disrupts Context-Dependent Memory

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    Schwabe, Lars; Bohringer, Andreas; Wolf, Oliver T.

    2009-01-01

    Memory is facilitated when the retrieval context resembles the learning context. The brain structures underlying contextual influences on memory are susceptible to stress. Whether stress interferes with context-dependent memory is still unknown. We exposed healthy adults to stress or a control procedure before they learned an object-location task…

  14. 1,25-dihydroxyvitamin D3 impairs NF-κB activation in human naive B cells

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    Geldmeyer-Hilt, Kerstin; Heine, Guido; Hartmann, Bjoern; Baumgrass, Ria; Radbruch, Andreas; Worm, Margitta

    2011-01-01

    Highlights: → In naive B cells, VDR activation by calcitriol results in reduced NF-κB p105 and p50 protein expression. → Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-κB p65. → Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. → Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1α,25-dihydroxyvitamin D 3 (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-κB p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-κB mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-κB activation by interference with NF-κB p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

  15. 1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

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    Geldmeyer-Hilt, Kerstin, E-mail: kerstin.hilt@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Heine, Guido, E-mail: guido.heine@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Hartmann, Bjoern, E-mail: bjoern.hartmann@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Baumgrass, Ria, E-mail: baumgrass@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Radbruch, Andreas, E-mail: radbruch@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Worm, Margitta, E-mail: margitta.worm@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany)

    2011-04-22

    Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

  16. Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

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    Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

    2015-01-01

    Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

  17. A Context-Dependent Role for IL-21 in Modulating the Differentiation, Distribution, and Abundance of Effector and Memory CD8 T Cell Subsets.

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    Tian, Yuan; Cox, Maureen A; Kahan, Shannon M; Ingram, Jennifer T; Bakshi, Rakesh K; Zajac, Allan J

    2016-03-01

    The activation of naive CD8 T cells typically results in the formation of effector cells (TE) as well as phenotypically distinct memory cells that are retained over time. Memory CD8 T cells can be further subdivided into central memory, effector memory (TEM), and tissue-resident memory (TRM) subsets, which cooperate to confer immunological protection. Using mixed bone marrow chimeras and adoptive transfer studies in which CD8 T cells either do or do not express IL-21R, we discovered that under homeostatic or lymphopenic conditions IL-21 acts directly on CD8 T cells to favor the accumulation of TE/TEM populations. The inability to perceive IL-21 signals under competitive conditions also resulted in lower levels of TRM phenotype cells and reduced expression of granzyme B in the small intestine. IL-21 differentially promoted the expression of the chemokine receptor CX3CR1 and the integrin α4β7 on CD8 T cells primed in vitro and on circulating CD8 T cells in the mixed bone marrow chimeras. The requirement for IL-21 to establish CD8 TE/TEM and TRM subsets was overcome by acute lymphocytic choriomeningitis virus infection; nevertheless, memory virus-specific CD8 T cells remained dependent on IL-21 for optimal accumulation in lymphopenic environments. Overall, this study reveals a context-dependent role for IL-21 in sustaining effector phenotype CD8 T cells and influencing their migratory properties, accumulation, and functions. Copyright © 2016 by The American Association of Immunologists, Inc.

  18. The Benefit of Attention-to-Memory Depends on the Interplay of Memory Capacity and Memory Load

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    Lim, Sung-Joo; Wöstmann, Malte; Geweke, Frederik; Obleser, Jonas

    2018-01-01

    Humans can be cued to attend to an item in memory, which facilitates and enhances the perceptual precision in recalling this item. Here, we demonstrate that this facilitating effect of attention-to-memory hinges on the overall degree of memory load. The benefit an individual draws from attention-to-memory depends on her overall working memory performance, measured as sensitivity (d′) in a retroactive cue (retro-cue) pitch discrimination task. While listeners maintained 2, 4, or 6 auditory syllables in memory, we provided valid or neutral retro-cues to direct listeners’ attention to one, to-be-probed syllable in memory. Participants’ overall memory performance (i.e., perceptual sensitivity d′) was relatively unaffected by the presence of valid retro-cues across memory loads. However, a more fine-grained analysis using psychophysical modeling shows that valid retro-cues elicited faster pitch-change judgments and improved perceptual precision. Importantly, as memory load increased, listeners’ overall working memory performance correlated with inter-individual differences in the degree to which precision improved (r = 0.39, p = 0.029). Under high load, individuals with low working memory profited least from attention-to-memory. Our results demonstrate that retrospective attention enhances perceptual precision of attended items in memory but listeners’ optimal use of informative cues depends on their overall memory abilities. PMID:29520246

  19. The Benefit of Attention-to-Memory Depends on the Interplay of Memory Capacity and Memory Load

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    Sung-Joo Lim

    2018-02-01

    Full Text Available Humans can be cued to attend to an item in memory, which facilitates and enhances the perceptual precision in recalling this item. Here, we demonstrate that this facilitating effect of attention-to-memory hinges on the overall degree of memory load. The benefit an individual draws from attention-to-memory depends on her overall working memory performance, measured as sensitivity (d′ in a retroactive cue (retro-cue pitch discrimination task. While listeners maintained 2, 4, or 6 auditory syllables in memory, we provided valid or neutral retro-cues to direct listeners’ attention to one, to-be-probed syllable in memory. Participants’ overall memory performance (i.e., perceptual sensitivity d′ was relatively unaffected by the presence of valid retro-cues across memory loads. However, a more fine-grained analysis using psychophysical modeling shows that valid retro-cues elicited faster pitch-change judgments and improved perceptual precision. Importantly, as memory load increased, listeners’ overall working memory performance correlated with inter-individual differences in the degree to which precision improved (r = 0.39, p = 0.029. Under high load, individuals with low working memory profited least from attention-to-memory. Our results demonstrate that retrospective attention enhances perceptual precision of attended items in memory but listeners’ optimal use of informative cues depends on their overall memory abilities.

  20. The Naive Central Banker

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    Marcelo de Carvalho Griebeler

    2015-09-01

    Full Text Available There has been in some countries a trend of assigning other functions to central banks besides price stability. The most suggested function to be added to monetary authority’s obligations is to pursue economic growth or full employment. In this paper we characterize the behavior and analyse the optimal monetary policy of, what we call, a naive central banker. We describe the naive behavior as one that does face the inflation-unemployment trade-off, but it tries to minimize both variables simultaneously. Our findings, both under discretion and commitment, indicate that the naive central banker delivers lower expected inflation and inflation variance than the benchmark behavior whenever the economy is rigid enough. However, the degree of conservativeness also affects this result, such that the less conservative the naive policymaker, the more rigidity is necessary.

  1. How aging affects sleep-dependent memory consolidation?

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    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  2. Naive Physics Perplex

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    Davis, Ernest

    1998-01-01

    The "Naive Physics Manifesto" of Pat Hayes (1978) proposes a large-scale project to develop a formal theory encompassing the entire knowledge of physics of naive reasoners, expressed in a declarative symbolic form. The theory is organized in clusters of closely interconnected concepts and axioms. More recent work on the representation of commonsense physical knowledge has followed a somewhat different methodology. The goal has been to develop a competence theory powerful enough to justify com...

  3. Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

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    Shicheng Su; Ling Lin; Yunjie Zeng; Nengtai Ouyang; Xiuying Cui; Herui Yao; Fengxi Su; Jian-dong Huang; Judy Lieberman; Qiang Liu; Erwei Song; Jianyou Liao; Jiang Liu; Di Huang; Chonghua He; Fei Chen; LinBing Yang; Wei Wu; Jianing Chen

    2017-01-01

    The origin of tumor-infiltrating Tregs,critical mediators of tumor immunosuppression,is unclear.Here,we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires,while hardly overlap with circulating Tregs,suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs.Furthermore,the abundance of naive CD4+ T cells and Tregs is closely correlated,both indicating poor prognosis for breast cancer patients.Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCLl8-producing macrophages.Moreover,adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner.In human breast cancer xenografts in humanized mice,blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3,a CCL18 receptor,significantly reduces intratumoral Tregs and inhibits tumor progression.These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ.Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy.

  4. Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

    Science.gov (United States)

    Su, Shicheng; Liao, Jianyou; Liu, Jiang; Huang, Di; He, Chonghua; Chen, Fei; Yang, LinBing; Wu, Wei; Chen, Jianing; Lin, Ling; Zeng, Yunjie; Ouyang, Nengtai; Cui, Xiuying; Yao, Herui; Su, Fengxi; Huang, Jian-dong; Lieberman, Judy; Liu, Qiang; Song, Erwei

    2017-01-01

    The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4+ T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCL18-producing macrophages. Moreover, adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner. In human breast cancer xenografts in humanized mice, blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3, a CCL18 receptor, significantly reduces intratumoral Tregs and inhibits tumor progression. These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ. Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy. PMID:28290464

  5. Sleep-dependent facilitation of episodic memory details.

    Science.gov (United States)

    van der Helm, Els; Gujar, Ninad; Nishida, Masaki; Walker, Matthew P

    2011-01-01

    While a role for sleep in declarative memory processing is established, the qualitative nature of this consolidation benefit, and the physiological mechanisms mediating it, remain debated. Here, we investigate the impact of sleep physiology on characteristics of episodic memory using an item- (memory elements) and context- (contextual details associated with those elements) learning paradigm; the latter being especially dependent on the hippocampus. Following back-to-back encoding of two word lists, each associated with a different context, participants were assigned to either a Nap-group, who obtained a 120-min nap, or a No Nap-group. Six hours post-encoding, participants performed a recognition test involving item-memory and context-memory judgments. In contrast to item-memory, which demonstrated no between-group differences, a significant benefit in context-memory developed in the Nap-group, the extent of which correlated both with the amount of stage-2 NREM sleep and frontal fast sleep-spindles. Furthermore, a difference was observed on the basis of word-list order, with the sleep benefit and associated physiological correlations being selective for the second word-list, learned last (most proximal to sleep). These findings suggest that sleep may preferentially benefit contextual (hippocampal-dependent) aspects of memory, supported by sleep-spindle oscillations, and that the temporal order of initial learning differentially determines subsequent offline consolidation.

  6. Sleep-dependent facilitation of episodic memory details.

    Directory of Open Access Journals (Sweden)

    Els van der Helm

    Full Text Available While a role for sleep in declarative memory processing is established, the qualitative nature of this consolidation benefit, and the physiological mechanisms mediating it, remain debated. Here, we investigate the impact of sleep physiology on characteristics of episodic memory using an item- (memory elements and context- (contextual details associated with those elements learning paradigm; the latter being especially dependent on the hippocampus. Following back-to-back encoding of two word lists, each associated with a different context, participants were assigned to either a Nap-group, who obtained a 120-min nap, or a No Nap-group. Six hours post-encoding, participants performed a recognition test involving item-memory and context-memory judgments. In contrast to item-memory, which demonstrated no between-group differences, a significant benefit in context-memory developed in the Nap-group, the extent of which correlated both with the amount of stage-2 NREM sleep and frontal fast sleep-spindles. Furthermore, a difference was observed on the basis of word-list order, with the sleep benefit and associated physiological correlations being selective for the second word-list, learned last (most proximal to sleep. These findings suggest that sleep may preferentially benefit contextual (hippocampal-dependent aspects of memory, supported by sleep-spindle oscillations, and that the temporal order of initial learning differentially determines subsequent offline consolidation.

  7. Monitoring the initiation and kinetics of human dendritic cell-induced polarization of autologous naive CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Tammy Oth

    Full Text Available A crucial step in generating de novo immune responses is the polarization of naive cognate CD4+ T cells by pathogen-triggered dendritic cells (DC. In the human setting, standardized DC-dependent systems are lacking to study molecular events during the initiation of a naive CD4+ T cell response. We developed a TCR-restricted assay to compare different pathogen-triggered human DC for their capacities to instruct functional differentiation of autologous, naive CD4+ T cells. We demonstrated that this methodology can be applied to compare differently matured DC in terms of kinetics, direction, and magnitude of the naive CD4+ T cell response. Furthermore, we showed the applicability of this assay to study the T cell polarizing capacity of low-frequency blood-derived DC populations directly isolated ex vivo. This methodology for addressing APC-dependent instruction of naive CD4+ T cells in a human autologous setting will provide researchers with a valuable tool to gain more insight into molecular mechanisms occurring in the early phase of T cell polarization. In addition, it may also allow the study of pharmacological agents on DC-dependent T cell polarization in the human system.

  8. Circadian Oscillations within the Hippocampus Support Hippocampus-dependent Memory Processing

    Directory of Open Access Journals (Sweden)

    Kristin Lynn Eckel-Mahan

    2012-04-01

    Full Text Available The ability to sustain memories over long periods of time, sometimes even a lifetime, is one of the most remarkable properties of the brain. Much knowledge has been gained over the past few decades regarding the molecular correlates of memory formation. Once a memory is forged, however, the molecular events that provide permanence are as of yet unclear. Studies in multiple organisms have revealed that circadian rhythmicity is important for the formation, stability, and recall of memories [1]. The neuronal events that provide this link need to be explored further. This article will discuss the findings related to the circadian regulation of memory-dependent processes in the hippocampus. Specifically, the circadian-controlled MAP kinase and cAMP signal transduction pathway plays critical roles in the consolidation of hippocampus-dependent memory. A series of studies have revealed the circadian oscillation of this pathway within the hippocampus, an activity that is absent in memory-deficient, transgenic mice lacking Ca2+-stimulated adenylyl cyclases. Interference with these oscillations proceeding the cellular memory consolidation period impairs the persistence of hippocampus-dependent memory. These data suggest that the persistence of long-term memories may depend upon reactivation of this signal transduction pathway in the hippocampus during the circadian cycle. New data reveals the dependence of hippocampal oscillation in MAPK activity on the SCN, again underscoring the importance of this region in maintaining the circadian physiology of memory. Finally, the downstream ramification of these oscillations in terms of gene expression and epigenetics should be considered, as emerging evidence is pointing strongly to a circadian link between epigenetics and long term synaptic plasticity.

  9. Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory.

    Science.gov (United States)

    Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki

    2017-08-01

    We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.

  10. Working memory differences in long-distance dependency resolution

    Directory of Open Access Journals (Sweden)

    Bruno eNicenboim

    2015-03-01

    Full Text Available There is a wealth of evidence showing that increasing the distance between an argument and its head leads to more processing effort, namely, locality effects; these are usually associated with constraints in working memory (DLT: Gibson, 2000; activation-based model: Lewis and Vasishth, 2005. In SOV languages, however, the opposite effect has been found: antilocality (see discussion in Levy et al., 2013. Antilocality effects can be explained by the expectation-based approach as proposed by Levy (2008 or by the activation-based model of sentence processing as proposed by Lewis and Vasishth (2005.We report an eye-tracking and a self-paced reading study with sentences in Spanish together with measures of individual differences to examine the distinction between expectation- and memory-based accounts, and within memory-based accounts the further distinction between DLT and the activation-based model. The experiments show that (i antilocality effects as predicted by the expectation account appear only for high-capacity readers; (ii increasing dependency length by interposing material that modifies the head of the dependency (the verb produces stronger facilitation than increasing dependency length with material that does not modify the head; this is in agreement with the activation-based model but not with the expectation account; and (iii a possible outcome of memory load on low-capacity readers is the increase in regressive saccades (locality effects as predicted by memory-based accounts or, surprisingly, a speedup in the self-paced reading task; the latter consistent with good-enough parsing (Ferreira et al., 2002. In sum, the study suggests that individual differences in working memory capacity play a role in dependency resolution, and that some of the aspects of dependency resolution can be best explained with the activation-based model together with a prediction component.

  11. Working memory differences in long-distance dependency resolution

    Science.gov (United States)

    Nicenboim, Bruno; Vasishth, Shravan; Gattei, Carolina; Sigman, Mariano; Kliegl, Reinhold

    2015-01-01

    There is a wealth of evidence showing that increasing the distance between an argument and its head leads to more processing effort, namely, locality effects; these are usually associated with constraints in working memory (DLT: Gibson, 2000; activation-based model: Lewis and Vasishth, 2005). In SOV languages, however, the opposite effect has been found: antilocality (see discussion in Levy et al., 2013). Antilocality effects can be explained by the expectation-based approach as proposed by Levy (2008) or by the activation-based model of sentence processing as proposed by Lewis and Vasishth (2005). We report an eye-tracking and a self-paced reading study with sentences in Spanish together with measures of individual differences to examine the distinction between expectation- and memory-based accounts, and within memory-based accounts the further distinction between DLT and the activation-based model. The experiments show that (i) antilocality effects as predicted by the expectation account appear only for high-capacity readers; (ii) increasing dependency length by interposing material that modifies the head of the dependency (the verb) produces stronger facilitation than increasing dependency length with material that does not modify the head; this is in agreement with the activation-based model but not with the expectation account; and (iii) a possible outcome of memory load on low-capacity readers is the increase in regressive saccades (locality effects as predicted by memory-based accounts) or, surprisingly, a speedup in the self-paced reading task; the latter consistent with good-enough parsing (Ferreira et al., 2002). In sum, the study suggests that individual differences in working memory capacity play a role in dependency resolution, and that some of the aspects of dependency resolution can be best explained with the activation-based model together with a prediction component. PMID:25852623

  12. Grading Gradients: Evaluating Evidence for Time-dependent Memory Reorganization in Experimental Animals

    Directory of Open Access Journals (Sweden)

    Katherine G. Akers

    2009-01-01

    Full Text Available In humans, hippocampal damage typically produces temporally graded retrograde amnesia, with relative sparing of remote memories compared to recent memories. This observation led to the idea that as memories age, they are reorganized in a time-dependent manner. Here, we evaluate evidence for time-dependent memory reorganization in animal models. We conclude that, although hippocampal lesions may not always produce temporal gradients under all conditions, studies using alternate experimental approaches consistently support the idea that memories reorganize over time—becoming less dependent on the hippocampus and more dependent on a cortical network. We further speculate on the processes that drive memory reorganization such as sleep, memory reactivation, synaptic plasticity, and neurogenesis.

  13. Time-dependent effects of cardiovascular exercise on memory

    DEFF Research Database (Denmark)

    Roig, Marc; Thomas, Richard; Mang, Cameron S

    2016-01-01

    We present new evidence supporting the hypothesis that the effects of cardiovascular exercise on memory can be regulated in a time-dependent manner. When the exercise stimulus is temporally coupled with specific phases of the memory formation process, a single bout of cardiovascular exercise may...... be sufficient to improve memory. SUMMARY: The timing of exercise in relation to the information to be remembered is critical to maximize the effects of acute cardiovascular exercise on memory....

  14. Context-dependent decay of motor memories during skill acquisition.

    Science.gov (United States)

    Ingram, James N; Flanagan, J Randall; Wolpert, Daniel M

    2013-06-17

    Current models of motor learning posit that skill acquisition involves both the formation and decay of multiple motor memories that can be engaged in different contexts. Memory formation is assumed to be context dependent, so that errors most strongly update motor memories associated with the current context. In contrast, memory decay is assumed to be context independent, so that movement in any context leads to uniform decay across all contexts. We demonstrate that for both object manipulation and force-field adaptation, contrary to previous models, memory decay is highly context dependent. We show that the decay of memory associated with a given context is greatest for movements made in that context, with more distant contexts showing markedly reduced decay. Thus, both memory formation and decay are strongest for the current context. We propose that this apparently paradoxical organization provides a mechanism for optimizing performance. While memory decay tends to reduce force output, memory formation can correct for any errors that arise, allowing the motor system to regulate force output so as to both minimize errors and avoid unnecessary energy expenditure. The motor commands for any given context thus result from a balance between memory formation and decay, while memories for other contexts are preserved. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Neuronal Oscillations Indicate Sleep-dependent Changes in the Cortical Memory Trace.

    Science.gov (United States)

    Köster, Moritz; Finger, Holger; Kater, Maren-Jo; Schenk, Christoph; Gruber, Thomas

    2017-04-01

    Sleep promotes the consolidation of newly acquired associative memories. Here we used neuronal oscillations in the human EEG to investigate sleep-dependent changes in the cortical memory trace. The retrieval activity for object-color associations was assessed immediately after encoding and after 3 hr of sleep or wakefulness. Sleep had beneficial effects on memory performance and led to reduced event-related theta and gamma power during the retrieval of associative memories. Furthermore, event-related alpha suppression was attenuated in the wake group for memorized and novel stimuli. There were no sleep-dependent changes in retrieval activity for missed items or items retrieved without color. Thus, the sleep-dependent reduction in theta and gamma oscillations was specific for the retrieval of associative memories. In line with theoretical accounts on sleep-dependent memory consolidation, decreased theta may indicate reduced mediotemporal activity because of a transfer of information into neocortical networks during sleep, whereas reduced parietal gamma may reflect effects of synaptic downscaling. Changes in alpha suppression in the wake group possibly index reduced attentional resources that may also contribute to a lower memory performance in this group. These findings indicate that the consolidation of associative memories during sleep is associated with profound changes in the cortical memory trace and relies on multiple neuronal processes working in concert.

  16. Environmental context-dependent memory: a review and meta-analysis.

    Science.gov (United States)

    Smith, S M; Vela, E

    2001-06-01

    To address questions about human memory's dependence on the coincidental environmental contexts in which events occur, we review studies of incidental environmental context-dependent memory in humans and report a meta-analysis. Our theoretical approach to the issue stems from Glenberg's (1997) contention that introspective thought (e.g., remembering, conceptualizing) requires cognitive resources normally used to represent the immediate environment. We propose that if tasks encourage processing of noncontextual information (i.e., introspective thought) at input and/or at test, then both learning and memory will be less dependent on the ambient environmental contexts in which those activities occur. The meta-analysis showed that across all studies, environmental context effects were reliable, and furthermore, that the use of noncontextual cues during learning (overshadowing) and at test (outshining), as well as mental reinstatement of appropriate context cues at test, all reduce the effect of environmental manipulations. We conclude that environmental context-dependent memory effects are less likely to occur under conditions in which the immediate environment is likely to be suppressed.

  17. Effects of rolipram and zaprinast on learning and memory in the Morris water maze and radial arm maze tests in naive mice.

    Science.gov (United States)

    Akar, F; Mutlu, O; Celikyurt, I K; Ulak, G; Erden, F; Bektas, E; Tanyeri, P

    2015-02-01

    Inhibition of phosphodiesterase 5 (PDE) improved recognition memory and counteracted spatial learning impairment induced by nitric oxide synthase (NOS) inhibition in recent studies. Aim of this study was to investigate effects of rolipram, a PDE4 inhibitor and zaprinast, a PDE5 inhibitor, on learning and memory in Morris water maze (MWM) and radial arm maze (RAM) tests in naive mice. Male Balb-c mice were treated subchronically with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) for 6 days in the MWM test and acutely before the retention trial of radial arm maze test. Rolipram (0.05 and 0.1 mg/kg) significantly decreased escape latency between 2(nd) and 5(th) sessions, while zaprinast (10 mg/kg) significantly decreased escape latency only in 2(nd) session. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly increased time spent in escape platform's quadrant in probe trial of MWM test; only rolipram decreased mean distance to platform, while zaprinast had no effect on mean distance to platform. Zaprinast (3 and 10 mg/kg) significantly decreased number of errors compared to control group, while rolipram (0.05 and 0.1mg/kg) had no effect on number of errors in retention trial of RAM test. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly decreased time spent to complete retention trial (latency) compared to control group. Our study revealed that both zaprinast and rolipram enhanced spatial memory in MWM, while zaprinast seems to have more memory enhancing effects compared to rolipram in radial arm maze test. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Implicit and Explicit Memory Bias in Opiate Dependent, Abstinent and Normal Individuals

    Directory of Open Access Journals (Sweden)

    Jafar Hasani

    2013-07-01

    Full Text Available Objective: The aim of current research was to assess implicit and explicit memory bias to drug related stimuli in opiate Dependent, abstinent and normal Individuals. Method: Three groups including opiate Dependent, abstinent and normal Individuals (n=25 were selected by available sampling method. After matching on the base of age, education level and type of substance use all participants assessed by recognition task (explicit memory bias and stem completion task (implicit memory bias. Results: The analysis of data showed that opiate dependent and abstinent groups in comparison with normal individual had implicit memory bias, whereas in explicit memory only opiate dependent individuals showed bias. Conclusion: The identification of explicit and implicit memory governing addiction may have practical implications in diagnosis, treatment and prevention of substance abuse.

  19. T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents - Retention of naive T lymphocytes in HIV-infected adolescents

    NARCIS (Netherlands)

    Douglas, SD; Rudy, B; Muenz, L; Starr, SE; Campbell, DE; Wilson, C; Holland, C; Crowley-Nowick, P; Vermund, SH

    Background: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. Objective: To assess lymphocyte subsets in HIV-infected and high-risk

  20. Hierarchical mixtures of naive Bayes classifiers

    NARCIS (Netherlands)

    Wiering, M.A.

    2002-01-01

    Naive Bayes classifiers tend to perform very well on a large number of problem domains, although their representation power is quite limited compared to more sophisticated machine learning algorithms. In this pa- per we study combining multiple naive Bayes classifiers by using the hierar- chical

  1. Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

    OpenAIRE

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippoca...

  2. Effects of physical exercise on object recognition memory in adult rats of postnatal isoflurane exposures

    Directory of Open Access Journals (Sweden)

    Xiao-yan FANG

    2017-08-01

    Full Text Available Objective To investigate effects of physical exercise (PE on object recognition memory in adult rats of postnatal isoflurane (Iso exposures. Methods One hundred and ten postnatal 7-day SD rats (P7 were randomly divided into four groups: normal control group (Naive, Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks, Iso group (three times of 2-hour Iso exposure in P7, P9, and P11, and Iso+PE group (received PE in P21 after postnatal Iso exposures. In P67, behavioral testing was conducted including open field and object recognition task (ORT, recording the time (Discrimination Ratios, DR that rats spent on exploring each object, evaluating effects of PE on object recognition memory. Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05. Compared with Naive, there was no group difference in DR (P>0.05 for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034. Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group: P67, P=0.050, P=0.017; P95, P=0.037, P=0.019; in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036, but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004. Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group: P=0.022, P=0.011; but in P95, the DR of non- Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE: P=0.008, P=0.017. Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise

  3. Glucose enhancement of memory depends on initial thirst.

    Science.gov (United States)

    Scholey, Andrew B; Sünram-Lea, Sandra I; Greer, Joanna; Elliott, Jade; Kennedy, David O

    2009-12-01

    This double-blind, placebo-controlled study examined the influence of appetitive state on glucose enhancement of memory. Participants rated their mood, hunger and thirst, then consumed a 25 g glucose drink or a matched placebo 20 min prior to a verbal memory task. There was a double dissociation when the effects of thirst ratings and drink on subsequent memory performance were considered. Those who were initially less thirsty recalled significantly more words following glucose than placebo; those who were more thirsty recalled significantly fewer words after glucose than placebo. Glucose enhancement of memory may therefore critically depend on participants' initial thirst.

  4. Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption

    Directory of Open Access Journals (Sweden)

    Jeyamala Chandrasekaran

    2015-01-01

    Full Text Available Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES and (ii generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security.

  5. Context-Dependent Decay of Motor Memories during Skill Acquisition

    OpenAIRE

    Ingram, James?N.; Flanagan, J.?Randall; Wolpert, Daniel?M.

    2013-01-01

    Summary Current models of motor learning posit that skill acquisition involves both the formation and decay of multiple motor memories that can be engaged in different contexts [1?9]. Memory formation is assumed to be context dependent, so that errors most strongly update motor memories associated with the current context. In contrast, memory decay is assumed to be context independent, so that movement in any context leads to uniform decay across all contexts. We demonstrate that for both obj...

  6. Decreased numbers of CD4+ naive and effector memory T cells, and CD8+ naïve T cells, are associated with trichloroethylene exposure

    Directory of Open Access Journals (Sweden)

    H Dean eHosgood

    2012-01-01

    Full Text Available Trichloroethylene (TCE is a volatile chlorinated organic compound that is commonly used as a solvent for lipophilic compounds. Although recognized as an animal carcinogen, TCE’s carcinogenic potential in humans is still uncertain. We have carried out a cross-sectional study of 80 workers exposed to TCE and 96 unexposed controls matched on age and sex in Guangdong, China to study TCE’s early biologic effects. We previously reported that the total lymphocyte count and each of the major lymphocyte subsets (i.e., CD4+ T cells, CD8+ T cells, natural killer (NK cells, and B cells were decreased in TCE-exposed workers compared to controls, suggesting a selective effect on lymphoid progenitors and/or lymphocyte survival. To explore which T lymphocyte subsets are affected, we investigated the effect of TCE exposure on the numbers of CD4+ naïve and memory T cells, CD8+ naïve and memory T cells, and regulatory T cells by FACS analysis. Linear regression of each subset was used to test for differences between exposed workers and controls adjusting for potential confounders. We observed that CD4+ and CD8+ naïve T cell counts were about 8% (p = 0.056 and 17% (p = 0.0002 lower, respectively, among exposed workers. CD4+ effector memory T cell counts were decreased by about 20% among TCE exposed workers compared to controls (p = 0.001. The selective targeting of TCE on CD8+ naïve and possibly CD4+ naive T cells, and CD4+ effector memory T cells, provide further insights into the immunosuppression-related response of human immune cells upon TCE exposure.

  7. Cognitive dissonance resolution depends on episodic memory.

    Science.gov (United States)

    Chammat, Mariam; Karoui, Imen El; Allali, Sébastien; Hagège, Joshua; Lehongre, Katia; Hasboun, Dominique; Baulac, Michel; Epelbaum, Stéphane; Michon, Agnès; Dubois, Bruno; Navarro, Vincent; Salti, Moti; Naccache, Lionel

    2017-01-23

    The notion that past choices affect preferences is one of the most influential concepts of social psychology since its first report in the 50 s, and its theorization within the cognitive dissonance framework. In the free-choice paradigm (FCP) after choosing between two similarly rated items, subjects reevaluate chosen items as more attractive and rejected items as less attractive. However the relations prevailing between episodic memory and choice-induced preference change (CIPC) remain highly debated: is this phenomenon dependent or independent from memory of past choices? We solve this theoretical debate by demonstrating that CIPC occurs exclusively for items which were correctly remembered as chosen or rejected during the choice stage. We used a combination of fMRI and intra-cranial electrophysiological recordings to reveal a modulation of left hippocampus activity, a hub of episodic memory retrieval, immediately before the occurrence of CIPC during item reevaluation. Finally, we show that contrarily to a previous influential report flawed by a statistical artifact, this phenomenon is absent in amnesic patients for forgotten items. These results demonstrate the dependence of cognitive dissonance on conscious episodic memory. This link between current preferences and previous choices suggests a homeostatic function of this regulative process, aiming at preserving subjective coherence.

  8. Time-dependent effects of cortisol on the contextualization of emotional memories.

    Science.gov (United States)

    van Ast, Vanessa A; Cornelisse, Sandra; Meeter, Martijn; Joëls, Marian; Kindt, Merel

    2013-12-01

    The inability to store fearful memories into their original encoding context is considered to be an important vulnerability factor for the development of anxiety disorders like posttraumatic stress disorder. Altered memory contextualization most likely involves effects of the stress hormone cortisol, acting via receptors located in the memory neurocircuitry. Cortisol via these receptors induces rapid nongenomic effects followed by slower genomic effects, which are thought to modulate cognitive function in opposite, complementary ways. Here, we targeted these time-dependent effects of cortisol during memory encoding and tested subsequent contextualization of emotional and neutral memories. In a double-blind, placebo-controlled design, 64 men were randomly assigned to one of three groups: 1) received 10 mg hydrocortisone 30 minutes (rapid cortisol effects) before a memory encoding task; 2) received 10 mg hydrocortisone 210 minutes (slow cortisol) before a memory encoding task; or 3) received placebo at both times. During encoding, participants were presented with neutral and emotional words in unique background pictures. Approximately 24 hours later, context dependency of their memories was assessed. Recognition data revealed that cortisol's rapid effects impair emotional memory contextualization, while cortisol's slow effects enhance it. Neutral memory contextualization remained unaltered by cortisol, irrespective of the timing of the drug. This study shows distinct time-dependent effects of cortisol on the contextualization of specifically emotional memories. The results suggest that rapid effects of cortisol may lead to impaired emotional memory contextualization, while slow effects of cortisol may confer protection against emotional memory generalization. © 2013 Society of Biological Psychiatry.

  9. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

    International Nuclear Information System (INIS)

    Managlia, Elizabeth Z.; Landay, Alan; Al-Harthi, Lena

    2006-01-01

    Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NFκB. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFNγ, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator

  10. Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.

    Science.gov (United States)

    Glennie, Nelson D; Yeramilli, Venkata A; Beiting, Daniel P; Volk, Susan W; Weaver, Casey T; Scott, Phillip

    2015-08-24

    Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells. © 2015 Glennie et al.

  11. Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

    Science.gov (United States)

    Goodman, J; Leong, K-C; Packard, M G

    2015-12-17

    Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

  12. Effect of human bone marrow mesenchymal stromal cells on cytokine production by peripheral blood naive, memory, and effector T cells.

    Science.gov (United States)

    Laranjeira, Paula; Pedrosa, Monia; Pedreiro, Susana; Gomes, Joana; Martinho, Antonio; Antunes, Brigida; Ribeiro, Tania; Santos, Francisco; Trindade, Helder; Paiva, Artur

    2015-01-05

    The different distribution of T cells among activation/differentiation stages in immune disorders may condition the outcome of mesenchymal stromal cell (MSC)-based therapies. Indeed, the effect of MSCs in the different functional compartments of T cells is not completely elucidated. We investigated the effect of human bone marrow MSCs on naturally occurring peripheral blood functional compartments of CD4(+) and CD8(+) T cells: naive, central memory, effector memory, and effector compartments. For that, mononuclear cells (MNCs) stimulated with phorbol myristate acetate (PMA) plus ionomycin were cultured in the absence/presence of MSCs. The percentage of cells expressing tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), and interleukin-2 (IL-2), IL-17, IL-9, and IL-6 and the amount of cytokine produced were assessed by flow cytometry. mRNA levels of IL-4, IL-10, transforming growth factor-beta (TGF-β), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in purified CD4(+) and CD8(+) T cells, and phenotypic and mRNA expression changes induced by PMA + ionomycin stimulation in MSCs, were also evaluated. MSCs induced the reduction of the percentage of CD4(+) and CD8(+) T cells producing TNF-α, IFNγ, and IL-2 in all functional compartments, except for naive IFNγ(+)CD4(+) T cells. This inhibitory effect differentially affected CD4(+) and CD8(+) T cells as well as the T-cell functional compartments; remarkably, different cytokines showed distinct patterns of inhibition regarding both the percentage of producing cells and the amount of cytokine produced. Likewise, the percentages of IL-17(+), IL-17(+)TNF-α(+), and IL-9(+) within CD4(+) and CD8(+) T cells and of IL-6(+)CD4(+) T cells were decreased in MNC-MSC co-cultures. MSCs decreased IL-10 and increased IL-4 mRNA expression in stimulated CD4(+) and CD8(+) T cells, whereas TGF-β was reduced in CD8(+) and augmented in CD4(+) T cells, with no changes for CTLA4. Finally, PMA

  13. Social networks: Evolving graphs with memory dependent edges

    Science.gov (United States)

    Grindrod, Peter; Parsons, Mark

    2011-10-01

    The plethora of digital communication technologies, and their mass take up, has resulted in a wealth of interest in social network data collection and analysis in recent years. Within many such networks the interactions are transient: thus those networks evolve over time. In this paper we introduce a class of models for such networks using evolving graphs with memory dependent edges, which may appear and disappear according to their recent history. We consider time discrete and time continuous variants of the model. We consider the long term asymptotic behaviour as a function of parameters controlling the memory dependence. In particular we show that such networks may continue evolving forever, or else may quench and become static (containing immortal and/or extinct edges). This depends on the existence or otherwise of certain infinite products and series involving age dependent model parameters. We show how to differentiate between the alternatives based on a finite set of observations. To test these ideas we show how model parameters may be calibrated based on limited samples of time dependent data, and we apply these concepts to three real networks: summary data on mobile phone use from a developing region; online social-business network data from China; and disaggregated mobile phone communications data from a reality mining experiment in the US. In each case we show that there is evidence for memory dependent dynamics, such as that embodied within the class of models proposed here.

  14. Sleep-dependent memory consolidation--what can be learnt from children?

    Science.gov (United States)

    Wilhelm, I; Prehn-Kristensen, A; Born, J

    2012-08-01

    Extensive research has been accumulated demonstrating that sleep is essential for processes of memory consolidation in adults. In children and infants, a great capacity to learn and to memorize coincides with longer and more intense sleep. Here, we review the available data on the influence of sleep on memory consolidation in healthy children and infants, as well as in children with attention-deficit/hyperactivity disorder (ADHD) as a model of prefrontal impairment, and consider possible mechanisms underlying age-dependent differences. Findings indicate a major role of slow wave sleep (SWS) for processes of memory consolidation during early development. Importantly, longer and deeper SWS during childhood appears to produce a distinctly superior strengthening of hippocampus-dependent declarative memories, but concurrently prevents an immediate benefit from sleep for procedural memories, as typically observed in adults. Studies of ADHD children point toward an essential contribution of prefrontal cortex to the preferential consolidation of declarative memory during SWS. Developmental studies of sleep represent a particularly promising approach for characterizing the supra-ordinate control of memory consolidation during sleep by prefrontal-hippocampal circuitry underlying the encoding of declarative memory. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S; Ortiz, Carla; O'Connell, Samuel; Hess, Henry; Lord, Graham M; Noelle, Randolph

    2015-01-15

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B(mem)) are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area. Copyright © 2015 by The American Association of Immunologists, Inc.

  16. Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

    Science.gov (United States)

    Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

    2015-04-01

    Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

  17. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition

    Science.gov (United States)

    Rodríguez-Cortez, Virginia C.; del Pino-Molina, Lucia; Rodríguez-Ubreva, Javier; Ciudad, Laura; Gómez-Cabrero, David; Company, Carlos; Urquiza, José M.; Tegnér, Jesper; Rodríguez-Gallego, Carlos; López-Granados, Eduardo; Ballestar, Esteban

    2015-01-01

    Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals. PMID:26081581

  18. Multi criteria wrapper improvements to naive bayes learning

    OpenAIRE

    Cortizo Pérez, José Carlos; Giráldez Betrón, Juan Ignacio

    2006-01-01

    Feature subset selection using a wrapper means to perform a search for an optimal set of attributes using the Machine Learning Algorithm as a black box. The Naive Bayes Classifier is based on the assumption of independence among the values of the attributes given the class value. Consequently, its effectiveness may decrease when the attributes are interdependent. We present FBL, a wrapper that uses information about dependencies to guide the search for the optimal subset of features and we us...

  19. Context Dependent Effects of Ventral Tegmental Area Inactivation on Spatial Working Memory

    OpenAIRE

    Martig, Adria K.; Jones, Graham L.; Smith, Kelsey E.; Mizumori, Sheri J.Y.

    2009-01-01

    Rats were tested on a hippocampus dependent win-shift working memory task in familiar or novel environments after receiving bilateral ventral tegmental area infusions of baclofen. Baclofen infusion disrupted working memory performance in both familiar and novel environments. In addition, baclofen infusion selectively disrupted short-term working memory in the novel environment. This experiment confirms selective ventral tegmental area support of accurate performance during a context dependent...

  20. Sex differences in HIV effects on visual memory among substance-dependent individuals.

    Science.gov (United States)

    Keutmann, Michael K; Gonzalez, Raul; Maki, Pauline M; Rubin, Leah H; Vassileva, Jasmin; Martin, Eileen M

    2017-08-01

    HIV's effects on episodic memory have not been compared systematically between male and female substance-dependent individuals. We administered the Brief Visuospatial Memory Test-Revised (BVMT-R) to 280 substance-dependent HIV+ and HIV- men and women. Groups were comparable on demographic, substance use, and comorbid characteristics. There were no significant main effects of sex or HIV serostatus on BVMT-R performance, but HIV+ women performed significantly more poorly on delayed recall. This effect was most prominent among cocaine-dependent HIV+ women. Our findings are consistent with recent speculation that memory impairment may be more common among HIV+ women, particularly those with a history of cocaine dependence.

  1. HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

    Science.gov (United States)

    Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

    2011-01-01

    Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

  2. PENERAPAN ALGORITMA NAIVE BAYES UNTUK MENGKLASIFIKASI DATA NASABAH ASURANSI

    Directory of Open Access Journals (Sweden)

    Bustami Bustami

    2014-01-01

    Full Text Available Data mining adalah teknik yang memanfaatkan data dalam jumlah yang besar untuk memperoleh informasi berharga yang sebelumnya tidak diketahui dan dapat dimanfaatkan untuk pengambilan keputusan penting. Pada penelitian ini, penulis berusaha menambang data (data mining nasabah sebuah perusahaan asuransi untuk mengetahui lancar, kurang lancar atau tidak lancarnya nasabah tersebut. Data yang ada dianalisis menggunakan algoritma Naive Bayes. Naive Bayes merupakan salah satu meode pada probabilistic reasoning. Algoritma Naive Bayes bertujuan untuk melakukan klasifikasi data pada kelas tertentu, kemudian pola tersebut dapat digunakan untuk memperkirakan nasabah yang bergabung, sehingga perusahaan bisa mengambil keputusan menerima atau menolak calon nasabah tersebut. Kata Kunci : data mining, asuransi, klasifikasi, algoritma Naive Bayes

  3. Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval.

    Science.gov (United States)

    Lopez, Joëlle; Herbeaux, Karin; Cosquer, Brigitte; Engeln, Michel; Muller, Christophe; Lazarus, Christine; Kelche, Christian; Bontempi, Bruno; Cassel, Jean-Christophe; de Vasconcelos, Anne Pereira

    2012-04-01

    According to systems consolidation, as hippocampal-dependent memories mature over time, they become additionally (or exclusively) dependent on extra-hippocampal structures. We assessed the recruitment of hippocampal and cortical structures on remote memory retrieval in a performance-degradation resistant (PDR; no performance degradation with time) versus performance-degradation prone (PDP; performance degraded with time) context. Using a water-maze task in two contexts with a hidden platform and three control conditions (home cage, visible platform with or without access to distal cues), we compared neuronal activation (c-Fos imaging) patterns in the dorsal hippocampus and the medial prefrontal cortex (mPFC) after the retrieval of recent (5 days) versus remote (25 days) spatial memory. In the PDR context, the hippocampus exhibited greater c-Fos protein expression on remote than recent memory retrieval, be it in the visible or hidden platform group. In the PDP context, hippocampal activation increased at the remote time point and only in the hidden platform group. In the anterior cingulate cortex, c-Fos expression was greater for remote than for recent memory retrieval and only in the PDR context. The necessity of the mPFC for remote memory retrieval in the PDR context was confirmed using region-specific lidocaine inactivation, which had no impact on recent memory. Conversely, inactivation of the dorsal hippocampus impaired both recent and remote memory in the PDR context, and only recent memory in the PDP context, in which remote memory performance was degraded. While confirming that neuronal circuits supporting spatial memory consolidation are reorganized in a time-dependent manner, our findings further indicate that mPFC and hippocampus recruitment (i) depends on the content and perhaps the strength of the memory and (ii) may be influenced by the environmental conditions (e.g., cue saliency, complexity) in which memories are initially formed and subsequently

  4. Visual memory performance for color depends on spatiotemporal context.

    Science.gov (United States)

    Olivers, Christian N L; Schreij, Daniel

    2014-10-01

    Performance on visual short-term memory for features has been known to depend on stimulus complexity, spatial layout, and feature context. However, with few exceptions, memory capacity has been measured for abruptly appearing, single-instance displays. In everyday life, objects often have a spatiotemporal history as they or the observer move around. In three experiments, we investigated the effect of spatiotemporal history on explicit memory for color. Observers saw a memory display emerge from behind a wall, after which it disappeared again. The test display then emerged from either the same side as the memory display or the opposite side. In the first two experiments, memory improved for intermediate set sizes when the test display emerged in the same way as the memory display. A third experiment then showed that the benefit was tied to the original motion trajectory and not to the display object per se. The results indicate that memory for color is embedded in a richer episodic context that includes the spatiotemporal history of the display.

  5. Chewing gum and context-dependent memory effects: a re-examination.

    Science.gov (United States)

    Miles, Christopher; Johnson, Andrew J

    2007-03-01

    Two experiments re-examined whether chewing spearmint gum affects initial word learning and/or immediate recall for a word list. Both experiments failed to show effects of chewing gum at learning or recall, nor did they suggest that chewing gum produces a context-dependent memory effect. This was true when extraneous contextual cues at learning and recall were minimised (Experiment 2). Together, the data are inconsistent with [Wilkinson, L., Scholey, A. & Wesnes, K. (2002). Chewing gum selectively improves aspects of memory in healthy volunteers. Appetite, 38, 235-236.] claim that chewing gum aids immediate recall of visually presented words. Our results are consistent with [Baker, J. R., Bezance, J. B., Zellaby, E. & Aggleton, J. P. (2004). Chewing gum can produce context-dependent effects upon memory. Appetite, 43, 207-210.] finding that chewing gum of itself is not a sufficient condition to provoke context-dependent learning with immediate testing.

  6. Emergence of task-dependent representations in working memory circuits

    Directory of Open Access Journals (Sweden)

    Cristina eSavin

    2014-05-01

    Full Text Available A wealth of experimental evidence suggests that working memory circuits preferentially represent information that is behaviorally relevant. Still, we are missing a mechanistic account of how these representations come about. Here we provide a simple explanation for a range of experimental findings, in light of prefrontal circuits adapting to task constraints by reward-dependent learning. In particular, we model a neural network shaped by reward-modulated spike-timing dependent plasticity (r-STDP and homeostatic plasticity (intrinsic excitability and synaptic scaling. We show that the experimentally-observed neural representations naturally emerge in an initially unstructured circuit as it learns to solve several working memory tasks. These results point to a critical, and previously unappreciated, role for reward-dependent learning in shaping prefrontal cortex activity.

  7. Genetic Disruption of the Core Circadian Clock Impairs Hippocampus-Dependent Memory

    Science.gov (United States)

    Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R.

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1[superscript -/-] mice, which are arrhythmic…

  8. Persistent expansion of CD4(+) effector memory T cells in Wegener's granulomatosis

    NARCIS (Netherlands)

    Abdulahad, W. H.; van der Geld, Y. M.; Stegeman, C. A.; Kallenberg, C. G. M.

    In order to test the hypothesis that Wegener's granulomatosis (WG) is associated with an ongoing immune effector response, even in remission, we examined the distribution of peripheral naive and memory T-lymphocytes in this disease, and analyzed the function-related phenotypes of the memory T-cell

  9. Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

    Science.gov (United States)

    Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

    2009-03-01

    To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

  10. Sophisticating a naive Liapunov function

    International Nuclear Information System (INIS)

    Smith, D.; Lewins, J.D.

    1985-01-01

    The art of the direct method of Liapunov to determine system stability is to construct a suitable Liapunov or V function where V is to be positive definite (PD), to shrink to a center, which may be conveniently chosen as the origin, and where V is the negative definite (ND). One aid to the art is to solve an approximation to the system equations in order to provide a candidate V function. It can happen, however, that the V function is not strictly ND but vanishes at a finite number of isolated points. Naively, one anticipates that stability has been demonstrated since the trajectory of the system at such points is only momentarily tangential and immediately enters a region of inward directed trajectories. To demonstrate stability rigorously requires the construction of a sophisticated Liapunov function from what can be called the naive original choice. In this paper, the authors demonstrate the method of perturbing the naive function in the context of the well-known second-order oscillator and then apply the method to a more complicated problem based on a prompt jump model for a nuclear fission reactor

  11. Depletion of naive CD4 T cells by CXCR4-using HIV-1 variants occurs mainly through increased T-cell death and activation

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Otto, Sigrid A.; Hamann, Dörte; Roos, Marijke Th L.; Schuitemaker, Hanneke; de Boer, Rob J.; Miedema, Frank

    2003-01-01

    Objective: Using SCID-Hu mice models and in vitro culture systems, it has been shown that syncytium inducing/CXCR4 using (X4) HIV-1 variants affect thymic function through infection and killing of CXCR4 thymocytes. The effect of X4-emergence on naive, memory and effector T-cell subset kinetics in

  12. Context-dependent memory and mood

    OpenAIRE

    Løhre, Erik

    2011-01-01

    This thesis examined the effects of affective state (mood) on context-dependent memory. In the so-called context-change paradigm, participants learn two lists of words, and their internal context is either changed or kept constant between the two lists. The usual finding in this paradigm is that participants remember fewer words from the first list, but more words from the second list when context is changed compared to when it is kept constant. To see whether these effects are influenced by ...

  13. Memory in Microbes: Quantifying History-Dependent Behavior in a Bacterium

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Denise M.; Fontaine-Bodin, Lisa; Bischofs, Ilka; Price, Gavin; Keasling, Jay; Arkin, Adam P.

    2007-11-15

    Memory is usually associated with higher organisms rather than bacteria. However, evidence is mounting that many regulatory networks within bacteria are capable of complex dynamics and multi-stable behaviors that have been linked to memory in other systems. Moreover, it is recognized that bacteria that have experienced different environmental histories may respond differently to current conditions. These"memory" effects may be more than incidental to the regulatory mechanisms controlling acclimation or to the status of the metabolic stores. Rather, they may be regulated by the cell and confer fitness to the organism in the evolutionary game it participates in. Here, we propose that history-dependent behavior is a potentially important manifestation of memory, worth classifying and quantifying. To this end, we develop an information-theory based conceptual framework for measuring both the persistence of memory in microbes and the amount of information about the past encoded in history-dependent dynamics. This method produces a phenomenologicalmeasure of cellular memory without regard to the specific cellular mechanisms encoding it. We then apply this framework to a strain of Bacillus subtilis engineered to report on commitment to sporulation and degradative enzyme (AprE) synthesisand estimate the capacity of these systems and growth dynamics to"remember" 10 distinct cell histories prior to application of a common stressor. The analysis suggests that B. subtilis remembers, both in short and long term, aspects of its cellhistory, and that this memory is distributed differently among the observables. While this study does not examine the mechanistic bases for memory, it presents a framework for quantifying memory in cellular behaviors and is thus a starting point for studying new questions about cellular regulation and evolutionary strategy.

  14. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children.

    Science.gov (United States)

    Baym, Carol L; Khan, Naiman A; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Moore, R Davis; Scudder, Mark R; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

    2014-05-01

    Studies in rodents and older humans have shown that the hippocampus-a brain structure critical to relational/associative memory-has remarkable plasticity as a result of lifestyle factors (eg, exercise). However, the effect of dietary intake on hippocampal-dependent memory during childhood has remained unexamined. We investigated the cross-sectional relation of dietary components characteristic of the Western diet, including saturated fatty acids (SFAs), omega-3 (n-3) fatty acids, and refined sugar, with hippocampal-dependent relational memory in prepubescent children. Participants aged 7-9 y (n = 52) reported their dietary intake by using the Youth-Adolescent Food-Frequency Questionnaire and completed memory tasks designed to assess relational (hippocampal-dependent) and item (hippocampal-independent) memory. Performance on the memory tasks was assessed with both direct (accuracy) and indirect (eye movement) measures. Partial correlations adjusted for body mass index showed a positive relation between relational memory accuracy and intake of omega-3 fatty acids and a negative relation of both relational and item memory accuracy with intake of SFAs. Potential confounding factors of age, sex, intelligence quotient, socioeconomic status, pubertal timing, and aerobic fitness (maximal oxygen volume) were not significantly related to any of the dietary intake measures. Eye movement measures of relational memory (preferential viewing to the target stimulus) showed a negative relation with intake of added sugar. SFA intake was negatively associated with both forms of memory, whereas omega-3 fatty acid intake was selectively positively associated with hippocampal-dependent relational memory. These findings are among the first to show a link between habitual dietary intake and cognitive health as pertaining to hippocampal function in childhood. The Fitness Improves Thinking Kids (FITKids) and FITKids2 trials were registered at www.clinicaltrials.gov as NCT01334359 and NCT

  15. Non-Dependent and Dependent Daily Cannabis Users Differ in Mental Health but Not Prospective Memory Ability

    OpenAIRE

    Ruth Braidwood; Samantha Mansell; Jon Waldron; Peter G. Rendell; Sunjeev K. Kamboj; H. Valerie Curran

    2018-01-01

    Research suggests that daily cannabis users have impaired memory for past events, but it is not clear whether they are also impaired in prospective memory (PM) for future events. The present study examined PM in daily cannabis users who were either dependent (n = 18) or non-dependent (n = 18), and compared them with non-using controls (n = 18). The effect of future event simulation (FES) on PM performance was also examined. Participants were matched across groups on age, gender, and highest l...

  16. Theta oscillations at encoding mediate the context-dependent nature of human episodic memory.

    Science.gov (United States)

    Staudigl, Tobias; Hanslmayr, Simon

    2013-06-17

    Human episodic memory is highly context dependent. Therefore, retrieval benefits when a memory is recalled in the same context compared to a different context. This implies that items and contexts are bound together during encoding, such that the reinstatement of the initial context at test improves retrieval. Animal studies suggest that theta oscillations and theta-to-gamma cross-frequency coupling modulate such item-context binding, but direct evidence from humans is scarce. We investigated this issue by manipulating the overlap of contextual features between encoding and retrieval. Participants studied words superimposed on movie clips and were later tested by presenting the word with either the same or a different movie. The results show that memory performance and the oscillatory correlates of memory formation crucially depend on the overlap of the context between encoding and test. When the context matched, high theta power during encoding was related to successful recognition, whereas the opposite pattern emerged in the context-mismatch condition. In addition, cross-frequency coupling analysis revealed a context-dependent theta-to-gamma memory effect specifically in the left hippocampus. These results reveal for the first time that context-dependent episodic memory effects are mediated by theta oscillatory activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.

    Science.gov (United States)

    Joshi, Nikhil S; Cui, Weiguo; Dominguez, Claudia X; Chen, Jonathan H; Hand, Timothy W; Kaech, Susan M

    2011-10-15

    Memory CD8 T cells acquire effector memory cell properties after reinfection and may reach terminally differentiated, senescent states ("Hayflick limit") after multiple infections. The signals controlling this process are not well understood, but we found that the degree of secondary effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and preexisting memory CD8 T cell number (i.e., primary memory CD8 T cell precursor frequency) present during secondary infection. Compared with naive cells, memory CD8 T cells were predisposed toward terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of Ag. TE cell formation after secondary (2°) or tertiary infections was dependent on increased T-bet expression because T-bet(+/-) cells were resistant to these phenotypic changes. Larger numbers of preexisting memory CD8 T cells limited the duration of 2° infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2° TE CD8 T cells that formed. Together, these data show that over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with Ag or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by preexisting memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies.

  18. Memory in microbes: quantifying history-dependent behavior in a bacterium.

    Directory of Open Access Journals (Sweden)

    Denise M Wolf

    2008-02-01

    Full Text Available Memory is usually associated with higher organisms rather than bacteria. However, evidence is mounting that many regulatory networks within bacteria are capable of complex dynamics and multi-stable behaviors that have been linked to memory in other systems. Moreover, it is recognized that bacteria that have experienced different environmental histories may respond differently to current conditions. These "memory" effects may be more than incidental to the regulatory mechanisms controlling acclimation or to the status of the metabolic stores. Rather, they may be regulated by the cell and confer fitness to the organism in the evolutionary game it participates in. Here, we propose that history-dependent behavior is a potentially important manifestation of memory, worth classifying and quantifying. To this end, we develop an information-theory based conceptual framework for measuring both the persistence of memory in microbes and the amount of information about the past encoded in history-dependent dynamics. This method produces a phenomenological measure of cellular memory without regard to the specific cellular mechanisms encoding it. We then apply this framework to a strain of Bacillus subtilis engineered to report on commitment to sporulation and degradative enzyme (AprE synthesis and estimate the capacity of these systems and growth dynamics to 'remember' 10 distinct cell histories prior to application of a common stressor. The analysis suggests that B. subtilis remembers, both in short and long term, aspects of its cell history, and that this memory is distributed differently among the observables. While this study does not examine the mechanistic bases for memory, it presents a framework for quantifying memory in cellular behaviors and is thus a starting point for studying new questions about cellular regulation and evolutionary strategy.

  19. Memory in microbes: quantifying history-Dependent behavior in a bacterium.

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Denise M.; Fontaine-Bodin, Lisa; Bischofs, Ilka; Price, Gavin; Keaslin, Jay; Arkin, Adam P.

    2007-11-15

    Memory is usually associated with higher organisms rather than bacteria. However, evidence is mounting that many regulatory networks within bacteria are capable of complex dynamics and multi-stable behaviors that have been linked to memory in other systems. Moreover, it is recognized that bacteria that have experienced different environmental histories may respond differently to current conditions. These"memory" effects may be more than incidental to the regulatory mechanisms controlling acclimation or to the status of the metabolic stores. Rather, they may be regulated by the cell and confer fitness to the organism in the evolutionary game it participates in. Here, we propose that history-dependent behavior is a potentially important manifestation of memory, worth classifying and quantifying. To this end, we develop an information-theory based conceptual framework for measuring both the persistence of memory in microbes and the amount of information about the past encoded in history-dependent dynamics. This method produces a phenomenological measure of cellular memory without regard to the specific cellular mechanisms encoding it. We then apply this framework to a strain of Bacillus subtilis engineered to report on commitment to sporulation and degradative enzyme (AprE) synthesis and estimate the capacity of these systems and growth dynamics to 'remember' 10 distinct cell histories prior to application of a common stressor. The analysis suggests that B. subtilis remembers, both in short and long term, aspects of its cell history, and that this memory is distributed differently among the observables. While this study does not examine the mechanistic bases for memory, it presents a framework for quantifying memory in cellular behaviors and is thus a starting point for studying new questions about cellular regulation and evolutionary strategy.

  20. Yugoslav Naive Art and Popular Culture

    Directory of Open Access Journals (Sweden)

    Meta Kordiš

    2009-12-01

    After the Second World War, the Yugoslav socialist state also strove to equalize and democratize society through art by minimizing the differences between the producers and consumers of art. Such a policy led to the decentralization of culture by forming various cultural and artistic institutions and by holding cultural events and spectacles in the countryside and peripheral areas. Through these various informal ideological mechanisms, the state apparatus exercised its authority in socializing its people in the spirit of Yugoslav socialist self-management and the ideology of brotherhood and unity by joining together the producers and consumers of naive art from various ethnicities, cultures, and social classes. Unfortunately this transformed naive art at its peak of popularity into a decorative and souvenir artifact with a pastoral image and folklore motifs. The encouragement from the authorities on the one hand and the market on the other produced and reproduced simple art forms and narrative contents without a complex iconography, which were consumed uncritically and on a large scale. Consequently, this completely denied the core of naive art and resulted in its final devaluation.

  1. Echoic memory in pigeons.

    Science.gov (United States)

    Kretzschmar, Christina; Kalenscher, Tobias; Güntürkün, Onur; Kaernbach, Christian

    2008-10-01

    It is unknown whether birds are able to retain the memory of purely sensory auditory information such as white noise over an extended period of time. In a Pavlovian heart rate conditioning paradigm, four pigeons were trained to associate a mild electric shock with periodic random waveforms, and no shock with aperiodic noise. Periodic waveform detection requires echoic memory, i.e., the online retention of a waveform pattern over a limited time. Starting with 40ms, the waveform period was increased after successful learning until no significant stimulus discrimination could be found. Significant discrimination was achieved at periods of up to 2560ms. This is the first demonstration that echoic memory performance in birds is clearly superior to cats and gerbils, and comparable to naive human performance.

  2. Late protein synthesis-dependent phases in CTA long-term memory: BDNF requirement

    Directory of Open Access Journals (Sweden)

    Araceli eMartínez-Moreno

    2011-09-01

    Full Text Available It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memory when protein synthesis was inhibited. Our previous studies on the insular cortex (IC, a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA, have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis dependent in different time-windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 hours after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

  3. Learning and Memory Impairments in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Andersen, Per N.; Egeland, Jens; Øie, Merete

    2013-01-01

    There are relatively few studies on learning and delayed memory with attention-deficit/hyperactivity disorder (ADHD). The objective of the present study was to examine acquisition, free delayed memory, and recognition skills in medication naive children and adolescents aged 8-16 years with ADHD combined subtype (36 participants) and inattentive…

  4. Goal- and retrieval-dependent activity in the striatum during memory recognition.

    Science.gov (United States)

    Clos, Mareike; Schwarze, Ulrike; Gluth, Sebastian; Bunzeck, Nico; Sommer, Tobias

    2015-06-01

    The striatum has been associated with successful memory retrieval but the precise functional link still remains unclear. One hypothesis is that striatal activity reflects an active evaluation process of the retrieval outcome dependent on the current behavioral goals rather than being a consequence of memory reactivation. We have recently shown that the striatum also correlates with confidence in memory recognition, which could reflect high subjective value ascribed to high certainty decisions. To examine whether striatal activity during memory recognition reflects subjective value indeed, we conducted an fMRI study using a recognition memory paradigm in which the participants rated not only the recognition confidence but also indicated the pleasantness associated with the previous memory retrieval. The results demonstrated a high positive correlation between confidence and pleasantness both on the behavioral and brain activation level particularly in the striatum. As almost all of variance in the striatal confidence signal could be explained by experienced pleasantness, this part of the striatal memory recognition response probably corresponds to greater subjective value of high confidence responses. While perceived oldness was also strongly correlated with striatal activity, this activation pattern was clearly distinct from that associated with confidence and pleasantness and thus could not be explained by higher subjective value to detect "old" items. Together, these results show that at least two independent processes contribute to striatal activation in recognition memory: a more flexible evaluation response dependent on context and goals captured by memory confidence and a potentially retrieval-related response captured by perceived oldness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Formation of model-free motor memories during motor adaptation depends on perturbation schedule.

    Science.gov (United States)

    Orban de Xivry, Jean-Jacques; Lefèvre, Philippe

    2015-04-01

    Motor adaptation to an external perturbation relies on several mechanisms such as model-based, model-free, strategic, or repetition-dependent learning. Depending on the experimental conditions, each of these mechanisms has more or less weight in the final adaptation state. Here we focused on the conditions that lead to the formation of a model-free motor memory (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787-801, 2011), i.e., a memory that does not depend on an internal model or on the size or direction of the errors experienced during the learning. The formation of such model-free motor memory was hypothesized to depend on the schedule of the perturbation (Orban de Xivry JJ, Ahmadi-Pajouh MA, Harran MD, Salimpour Y, Shadmehr R. J Neurophysiol 109: 124-136, 2013). Here we built on this observation by directly testing the nature of the motor memory after abrupt or gradual introduction of a visuomotor rotation, in an experimental paradigm where the presence of model-free motor memory can be identified (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787-801, 2011). We found that relearning was faster after abrupt than gradual perturbation, which suggests that model-free learning is reduced during gradual adaptation to a visuomotor rotation. In addition, the presence of savings after abrupt introduction of the perturbation but gradual extinction of the motor memory suggests that unexpected errors are necessary to induce a model-free motor memory. Overall, these data support the hypothesis that different perturbation schedules do not lead to a more or less stabilized motor memory but to distinct motor memories with different attributes and neural representations. Copyright © 2015 the American Physiological Society.

  6. Dreaming of a Learning Task is Associated with Enhanced Sleep-Dependent Memory Consolidation

    Science.gov (United States)

    Wamsley, Erin J.; Tucker, Matthew; Payne, Jessica D.; Benavides, Joseph; Stickgold, Robert

    2010-01-01

    Summary It is now well established that post-learning sleep is beneficial for human memory performance [1–5]. Meanwhile, human and animal studies demonstrate that learning-related neural activity is re-expressed during post-training non-rapid eye movement sleep (NREM) [6–9]. NREM sleep processes appear to be particularly beneficial for hippocampus-dependent forms of memory [1–3, 10]. These observations suggest that learning triggers the reactivation and reorganization of memory traces during sleep, a systems-level process that in turn enhances behavioral performance. Here, we hypothesized that dreaming about a learning experience during NREM sleep would be associated with improved performance on a hippocampus-dependent spatial memory task. Subjects (n=99) were trained on a virtual navigation task, and then retested on the same task 5 hours after initial training. Improved performance at retest was strongly associated with task-related dream imagery during an intervening afternoon nap. Task-related thoughts during wakefulness, in contrast, did not predict improved performance. These observations suggest that sleep-dependent memory consolidation in humans is facilitated by the offline reactivation of recently formed memories, and furthermore, that dream experiences reflect this memory processing. That similar effects were not seen during wakefulness suggests that these mnemonic processes are specific to the sleep state. PMID:20417102

  7. A Combined Omics Approach to Generate the Surface Atlas of Human Naive CD4+ T Cells during Early T-Cell Receptor Activation.

    Science.gov (United States)

    Graessel, Anke; Hauck, Stefanie M; von Toerne, Christine; Kloppmann, Edda; Goldberg, Tatyana; Koppensteiner, Herwig; Schindler, Michael; Knapp, Bettina; Krause, Linda; Dietz, Katharina; Schmidt-Weber, Carsten B; Suttner, Kathrin

    2015-08-01

    Naive CD4(+) T cells are the common precursors of multiple effector and memory T-cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell-like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4(+) T cells and their changes during the early phase of T-cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy. Periodate oxidation and aniline-catalyzed oxime ligation technology was applied with subsequent quantitative liquid chromatography-tandem MS to generate a data set describing the surface proteome of primary human naive CD4(+) T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins. To independently confirm the proteomic data set and to analyze the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous data set, resulting in 229 surface proteins, which were expressed on naive unstimulated and activated CD4(+) T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation, and predicted subcellular localization, and correlated the proteomics result with this transcriptional data set. This extensive surface atlas provides an overall naive CD4(+) T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T-cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Context-dependent memory decay is evidence of effort minimization in motor learning: a computational study.

    Science.gov (United States)

    Takiyama, Ken

    2015-01-01

    Recent theoretical models suggest that motor learning includes at least two processes: error minimization and memory decay. While learning a novel movement, a motor memory of the movement is gradually formed to minimize the movement error between the desired and actual movements in each training trial, but the memory is slightly forgotten in each trial. The learning effects of error minimization trained with a certain movement are partially available in other non-trained movements, and this transfer of the learning effect can be reproduced by certain theoretical frameworks. Although most theoretical frameworks have assumed that a motor memory trained with a certain movement decays at the same speed during performing the trained movement as non-trained movements, a recent study reported that the motor memory decays faster during performing the trained movement than non-trained movements, i.e., the decay rate of motor memory is movement or context dependent. Although motor learning has been successfully modeled based on an optimization framework, e.g., movement error minimization, the type of optimization that can lead to context-dependent memory decay is unclear. Thus, context-dependent memory decay raises the question of what is optimized in motor learning. To reproduce context-dependent memory decay, I extend a motor primitive framework. Specifically, I introduce motor effort optimization into the framework because some previous studies have reported the existence of effort optimization in motor learning processes and no conventional motor primitive model has yet considered the optimization. Here, I analytically and numerically revealed that context-dependent decay is a result of motor effort optimization. My analyses suggest that context-dependent decay is not merely memory decay but is evidence of motor effort optimization in motor learning.

  9. Context-dependent memory decay is evidence of effort minimization in motor learning: A computational study

    Directory of Open Access Journals (Sweden)

    Ken eTakiyama

    2015-02-01

    Full Text Available Recent theoretical models suggest that motor learning includes at least two processes: error minimization and memory decay. While learning a novel movement, a motor memory of the movement is gradually formed to minimize the movement error between the desired and actual movements in each training trial, but the memory is slightly forgotten in each trial. The learning effects of error minimization trained with a certain movement are partially available in other non-trained movements, and this transfer of the learning effect can be reproduced by certain theoretical frameworks. Although most theoretical frameworks have assumed that a motor memory trained with a certain movement decays at the same speed during performing the trained movement as non-trained movements, a recent study reported that the motor memory decays faster during performing the trained movement than non-trained movements, i.e., the decay rate of motor memory is movement or context dependent. Although motor learning has been successfully modeled based on an optimization framework, e.g., movement error minimization, the type of optimization that can lead to context-dependent memory decay is unclear. Thus, context-dependent memory decay raises the question of what is optimized in motor learning. To reproduce context-dependent memory decay, I extend a motor primitive framework. Specifically, I introduce motor effort optimization into the framework because some previous studies have reported the existence of effort optimization in motor learning processes and no conventional motor primitive model has yet considered the optimization. Here, I analytically and numerically revealed that context-dependent decay is a result of motor effort optimization. My analyses suggest that context-dependent decay is not merely memory decay but is evidence of motor effort optimization in motor learning.

  10. Derivation of novel human ground state naive pluripotent stem cells.

    Science.gov (United States)

    Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S; Chomsky, Elad; Ben-Yosef, Dalit; Kalma, Yael; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Shipony, Zohar; Mukamel, Zohar; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Shwartz, Tamar; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima; Amit, Ido; Tanay, Amos; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

    2013-12-12

    Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation

  11. State-dependent memory effects using caffeine and placebo do not extend to metamemory.

    Science.gov (United States)

    Kelemen, William L; Creeley, Catherine E

    2003-01-01

    The authors examined the impact of caffeine on human memory and predictions of memory (i.e., metamemory). On Day 1, 83 college students drank a sweetened beverage containing either caffeine (4 mg/kg body weight) or a placebo before they studied 40 pairs of words. While the participants studied, they predicted their future memory performance for each word pair. On Day 2, the participants again received caffeine or a placebo before the memory test. The participants who drank the same beverage on both days (either caffeine or a placebo) recalled more word pairs than did those who drank different beverages (caffeine on 1 day and a placebo on the other day). In contrast, memory predictions were more accurate when the beverages did not match on both days. These data provide evidence for state-dependent memory when caffeine is used, but not for state-dependent metamemory. People's memory and their predictions of memory can be influenced in different ways if they drink caffeine before they study or take a test.

  12. Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection.

    Science.gov (United States)

    Grau, Morgan; Valsesia, Séverine; Mafille, Julien; Djebali, Sophia; Tomkowiak, Martine; Mathieu, Anne-Laure; Laubreton, Daphné; de Bernard, Simon; Jouve, Pierre-Emmanuel; Ventre, Erwan; Buffat, Laurent; Walzer, Thierry; Leverrier, Yann; Marvel, Jacqueline

    2018-05-15

    The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D. Using this marker, we described the increased functionalities of AI and IN memory CD8 T cells compared with naive cells, as shown by comprehensive analysis of cytokine secretion and gene expression. However, AI differed from IN memory CD8 T cells by their capacity to migrate to the lung parenchyma upon inflammation or infection, a process dependent on their expression of ITGA1/CD49a and ITGA4/CD49d integrins. Copyright © 2018 by The American Association of Immunologists, Inc.

  13. Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

    Science.gov (United States)

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

    2011-01-01

    It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes. PMID:21960964

  14. Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement.

    Science.gov (United States)

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2011-01-01

    It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

  15. Smoothness without smoothing: why Gaussian naive Bayes is not naive for multi-subject searchlight studies.

    Directory of Open Access Journals (Sweden)

    Rajeev D S Raizada

    Full Text Available Spatial smoothness is helpful when averaging fMRI signals across multiple subjects, as it allows different subjects' corresponding brain areas to be pooled together even if they are slightly misaligned. However, smoothing is usually not applied when performing multivoxel pattern-based analyses (MVPA, as it runs the risk of blurring away the information that fine-grained spatial patterns contain. It would therefore be desirable, if possible, to carry out pattern-based analyses which take unsmoothed data as their input but which produce smooth images as output. We show here that the Gaussian Naive Bayes (GNB classifier does precisely this, when it is used in "searchlight" pattern-based analyses. We explain why this occurs, and illustrate the effect in real fMRI data. Moreover, we show that analyses using GNBs produce results at the multi-subject level which are statistically robust, neurally plausible, and which replicate across two independent data sets. By contrast, SVM classifiers applied to the same data do not generate a replication, even if the SVM-derived searchlight maps have smoothing applied to them. An additional advantage of GNB classifiers for searchlight analyses is that they are orders of magnitude faster to compute than more complex alternatives such as SVMs. Collectively, these results suggest that Gaussian Naive Bayes classifiers may be a highly non-naive choice for multi-subject pattern-based fMRI studies.

  16. The Limited Capacity of Sleep-Dependent Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Gordon B Feld

    2016-09-01

    Full Text Available Sleep supports memory consolidation. However, the conceptually important influence of the amount of items encoded in a memory test on this effect has not been investigated. In two experiments, participants (n=101 learned lists of word-pairs varying in length (40, 160, 320 word-pairs in the evening before a night of sleep (sleep group or of sleep deprivation (wake group. After 36 h (including a night allowing recovery sleep retrieval was tested. Compared with wakefulness, post-learning sleep enhanced retention for the 160 word-pair condition (p < 0.01, importantly, this effect completely vanished for the 320 word-pair condition. This result indicates a limited capacity for sleep-dependent memory consolidation, which is consistent with an active system consolidation view on sleep’s role for memory, if it is complemented by processes of active forgetting and/or gist abstraction. Whereas the absolute benefit from sleep should have increased with increasing amounts of successfully encoded items, if sleep only passively protected memory from interference. Moreover, the finding that retention performance was significantly diminished for the 320 word-pair condition compared to the 160 word-pair condition in the sleep group, makes it tempting to speculate that with increasing loads of information encoded during wakefulness, sleep might favour processes of forgetting over consolidation.

  17. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.

    Science.gov (United States)

    Wang, Jichang; Xie, Gangcai; Singh, Manvendra; Ghanbarian, Avazeh T; Raskó, Tamás; Szvetnik, Attila; Cai, Huiqiang; Besser, Daniel; Prigione, Alessandro; Fuchs, Nina V; Schumann, Gerald G; Chen, Wei; Lorincz, Matthew C; Ivics, Zoltán; Hurst, Laurence D; Izsvák, Zsuzsanna

    2014-12-18

    Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents easily, although human naive-like cells have been artificially generated (rather than extracted) by coercion of human primed embryonic stem cells by modifying culture conditions or through transgenic modification. Here we show that a sub-population within cultures of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) manifests key properties of naive state cells. These naive-like cells can be genetically tagged, and are associated with elevated transcription of HERVH, a primate-specific endogenous retrovirus. HERVH elements provide functional binding sites for a combination of naive pluripotency transcription factors, including LBP9, recently recognized as relevant to naivety in mice. LBP9-HERVH drives hESC-specific alternative and chimaeric transcripts, including pluripotency-modulating long non-coding RNAs. Disruption of LBP9, HERVH and HERVH-derived transcripts compromises self-renewal. These observations define HERVH expression as a hallmark of naive-like hESCs, and establish novel primate-specific transcriptional circuitry regulating pluripotency.

  18. Spatial short-term memory is impaired in dependent betel quid chewers.

    Science.gov (United States)

    Chiu, Meng-Chun; Shen, Bin; Li, Shuo-Heng; Ho, Ming-Chou

    2016-08-01

    Betel quid is regarded as a human carcinogen by the World Health Organization. It remains unknown whether chewing betel quid has a chronic effect on healthy betel quid chewers' memory. The present study aims to investigate whether chewing betel quid can affect short-term memory (STM). Three groups of participants (24 dependent chewers, 24 non-dependent chewers, and 24 non-chewers) were invited to carry out the matrix span task, the object span task, and the digit span task. All span tasks' results were adopted to assess spatial STM, visual STM, and verbal STM, respectively. Besides, there are three set sizes (small, medium, and large) in each span task. For the matrix span task, results showed that the dependent chewers had worse performances than the non-dependent chewers and the non-chewers at medium and large set sizes. For the object span task and digit span task, there were no differences in between groups. In each group, recognition performances were worse with the increasing set size and showing successful manipulation of memory load. The current study provided the first evidence that dependent betel quid chewing can selectively impair spatial STM rather than visual STM and verbal STM. Theoretical and practical implications of this result are discussed.

  19. Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network.

    Science.gov (United States)

    Kalisch, Raffael; Korenfeld, Elian; Stephan, Klaas E; Weiskopf, Nikolaus; Seymour, Ben; Dolan, Raymond J

    2006-09-13

    In fear extinction, an animal learns that a conditioned stimulus (CS) no longer predicts a noxious stimulus [unconditioned stimulus (UCS)] to which it had previously been associated, leading to inhibition of the conditioned response (CR). Extinction creates a new CS-noUCS memory trace, competing with the initial fear (CS-UCS) memory. Recall of extinction memory and, hence, CR inhibition at later CS encounters is facilitated by contextual stimuli present during extinction training. In line with theoretical predictions derived from animal studies, we show that, after extinction, a CS-evoked engagement of human ventromedial prefrontal cortex (VMPFC) and hippocampus is context dependent, being expressed in an extinction, but not a conditioning, context. Likewise, a positive correlation between VMPFC and hippocampal activity is extinction context dependent. Thus, a VMPFC-hippocampal network provides for context-dependent recall of human extinction memory, consistent with a view that hippocampus confers context dependence on VMPFC.

  20. A Comprehensive Investigation of Memory Impairment in Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder

    Science.gov (United States)

    Rhodes, Sinead M.; Park, Joanne; Seth, Sarah; Coghill, David R.

    2012-01-01

    Background: We conducted a comprehensive and systematic assessment of memory functioning in drug-naive boys with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Methods: Boys performed verbal and spatial working memory (WM) component (storage and central executive) and verbal and spatial storage load tasks,…

  1. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children1234

    Science.gov (United States)

    Khan, Naiman A; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Moore, R Davis; Scudder, Mark R; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

    2014-01-01

    Background: Studies in rodents and older humans have shown that the hippocampus—a brain structure critical to relational/associative memory—has remarkable plasticity as a result of lifestyle factors (eg, exercise). However, the effect of dietary intake on hippocampal-dependent memory during childhood has remained unexamined. Objective: We investigated the cross-sectional relation of dietary components characteristic of the Western diet, including saturated fatty acids (SFAs), omega-3 (n−3) fatty acids, and refined sugar, with hippocampal-dependent relational memory in prepubescent children. Design: Participants aged 7–9 y (n = 52) reported their dietary intake by using the Youth-Adolescent Food-Frequency Questionnaire and completed memory tasks designed to assess relational (hippocampal-dependent) and item (hippocampal-independent) memory. Performance on the memory tasks was assessed with both direct (accuracy) and indirect (eye movement) measures. Results: Partial correlations adjusted for body mass index showed a positive relation between relational memory accuracy and intake of omega-3 fatty acids and a negative relation of both relational and item memory accuracy with intake of SFAs. Potential confounding factors of age, sex, intelligence quotient, socioeconomic status, pubertal timing, and aerobic fitness (maximal oxygen volume) were not significantly related to any of the dietary intake measures. Eye movement measures of relational memory (preferential viewing to the target stimulus) showed a negative relation with intake of added sugar. Conclusions: SFA intake was negatively associated with both forms of memory, whereas omega-3 fatty acid intake was selectively positively associated with hippocampal-dependent relational memory. These findings are among the first to show a link between habitual dietary intake and cognitive health as pertaining to hippocampal function in childhood. The Fitness Improves Thinking Kids (FITKids) and FITKids2 trials were

  2. Memory Effects and Coverage Dependence of Surface Diffusion in a Model Adsorption System

    DEFF Research Database (Denmark)

    Vattulainen, Ilpo Tapio; Ying, S. C.; Ala-Nissila, T.

    1999-01-01

    in tracer and collective diffusion. We show that memory effects can be very pronounced deep inside the ordered phases and in regions close to first and second order phase transition boundaries. Particular attention is paid to the details of the time dependence of memory effects. The memory effect in tracer......We study the coverage dependence of surface diffusion coefficients for a strongly interacting adsorption system O/W(110) via Monte Carlo simulations of a lattice-gas model. In particular, we consider the nature and emergence of memory effects as contained in the corresponding correlation factors...... diffusion is found to decay following a power law after an initial transient period. This behavior persists until the hydrodynamic regime is reached, after which the memory effect decays exponentially. The time required to reach the hydrodynamical regime and the related exponential decay is strongly...

  3. Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

    Science.gov (United States)

    Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

    2016-07-01

    Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Consolidation of an extinction memory depends on the unconditioned stimulus magnitude previously experienced during training.

    Science.gov (United States)

    Stollhoff, Nicola; Eisenhardt, Dorothea

    2009-07-29

    Here, we examine the role of the magnitude of the unconditioned stimulus (US) during classical conditioning in consolidation processes after memory retrieval. We varied the US durations during training and we test the impact of these variations on consolidation after memory retrieval with one or two conditioned stimulus-only trials. We found that the consolidation of an extinction memory depends on US duration during training and ruled out the possibility that this effect is attributable to differences in satiation after conditioning. We conclude that consolidation of an extinction memory is triggered only when the duration of the US reaches a critical threshold. This demonstrates that memory consolidation cannot be regarded as an isolated process depending solely on training conditions. Instead, it depends on the animal's previous experience as well.

  5. Evidence against memorial facilitation and context-dependent memory effects through the chewing of gum

    OpenAIRE

    Johnson, A.J.; Miles, C.

    2007-01-01

    The experiment examined the prediction that chewing gum at learning and/or recall facilitated subsequent word recall. Chewing gum at learning significantly impaired recall, indicating that the chewing of gum has a detrimental impact upon initial word encoding. In addition, a context-dependent memory effect was reported for those participants who both learned and recalled in the absence of gum, however a context dependent effect was not found with chewing gum. The findings contradict previous ...

  6. Memory and pattern storage in neural networks with activity dependent synapses

    Science.gov (United States)

    Mejias, J. F.; Torres, J. J.

    2009-01-01

    We present recently obtained results on the influence of the interplay between several activity dependent synaptic mechanisms, such as short-term depression and facilitation, on the maximum memory storage capacity in an attractor neural network [1]. In contrast with the case of synaptic depression, which drastically reduces the capacity of the network to store and retrieve activity patterns [2], synaptic facilitation is able to enhance the memory capacity in different situations. In particular, we find that a convenient balance between depression and facilitation can enhance the memory capacity, reaching maximal values similar to those obtained with static synapses, that is, without activity-dependent processes. We also argue, employing simple arguments, that this level of balance is compatible with experimental data recorded from some cortical areas, where depression and facilitation may play an important role for both memory-oriented tasks and information processing. We conclude that depressing synapses with a certain level of facilitation allow to recover the good retrieval properties of networks with static synapses while maintaining the nonlinear properties of dynamic synapses, convenient for information processing and coding.

  7. File list: Oth.Bld.10.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Oth.Bld.05.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory

    Science.gov (United States)

    Sanderson, David J.; Hindley, Emma; Smeaton, Emily; Denny, Nick; Taylor, Amy; Barkus, Chris; Sprengel, Rolf; Seeburg, Peter H.; Bannerman, David M.

    2011-01-01

    Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual–retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes. PMID:21378100

  10. Induction of IgG memory responses with polyvinylpyrrolidone (PVP) is antigen dose dependent

    International Nuclear Information System (INIS)

    Lite, H.S.; Braley-Mullen, H.

    1981-01-01

    Irradiated recipients of spleen cells from mice primed with a very low dose (0.0025 μ/g) of the thymus-independent (TI) antigen polyvinylpyrrolidone (PVP) produced PVP-specific IgG memory responses after secondary challenge with a T-dependent (TD) form of PVP, PVP-HRBC. The IgG memory responses induced by low doses of PVP were similar in magnitude to those induced by the TD antigen PVP-HRBC. The induction of IgG memory by the TI form of antigen was markedly dependent on the dose of PVP used to prime donor mice. Spleen cells from mice primed with an amount of PVP (0.25 μg) that induces an optimal primary IgM response did not produce significant IgG antibody after challenge with PVP-HRBC. The inability of higher doses of PVP to induce IgG memory may be due, at least in part, to the fact that such doses of PVP were found to induce tolerance in PVP-specific B cells and could suppress the induction of memory induced by PVP-HRBC. Low doses of PVP did not interfere with the induction of memory by PVP-HRBC. Expression of IgG memory responses in recipients of PVP-HRBC or low-dose PVP-primed cells was found to be T cell dependent. Moreover, only primed T cells could reconstitute the respnse of recipients of primed B cells, suggesting that the ability of PVP to induce IgG memory may be related to its ability to prime T helper cells. Expression of the IgG memory response in recipient mice also required the use of a TD antigen for secondary challenge, i.e., mice challenged with PVP did not develop IgG

  11. The role of cytokines in T-cell memory in health and disease.

    Science.gov (United States)

    Raeber, Miro E; Zurbuchen, Yves; Impellizzieri, Daniela; Boyman, Onur

    2018-05-01

    Upon stimulation with their cognate antigen, naive T cells undergo proliferation and differentiation into effector cells, followed by apoptosis or survival as precursors of long-lived memory cells. These phases of a T-cell response and the ensuing maintenance of memory T cells are shaped by cytokines, most notably interleukin-2 (IL-2), IL-7, and IL-15 that share the common γ chain (γ c ) cytokine receptor. Steady-state production of IL-7 and IL-15 is necessary for background proliferation and homeostatic survival of CD4 + and CD8 + memory T cells. During immune responses, augmented levels of IL-2, IL-15, IL-21, IL-12, IL-18, and type-I interferons determine the memory potential of antigen-specific effector CD8 + cells, while increased IL-2 and IL-15 cause bystander proliferation of heterologous CD4 + and CD8 + memory T cells. Limiting availability of γ c cytokines, reduction in regulatory T cells or IL-10, and persistence of inflammation or cognate antigen can result in memory T cells, which fail to become cytokine-dependent long-lived cells. Conversely, increased IL-7 and IL-15 can expand memory T cells, including pathogenic tissue-resident memory T cells, as seen in lymphopenia and certain chronic-inflammatory disorders and malignancies. These abovementioned factors impact immunotherapy and vaccines directed at memory T cells in cancer and chronic infection. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Evidence against memorial facilitation and context-dependent memory effects through the chewing of gum.

    Science.gov (United States)

    Johnson, Andrew J; Miles, Christopher

    2007-05-01

    The experiment examined the prediction that chewing gum at learning and/or recall facilitated subsequent word recall. Chewing gum at learning significantly impaired recall, indicating that the chewing of gum has a detrimental impact upon initial word encoding. In addition, a context-dependent memory effect was reported for those participants who both learned and recalled in the absence of gum; however, a context-dependent effect was not found with chewing gum. The findings contradict previous research.

  13. Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny.

    Science.gov (United States)

    Wimmer, M E; Briand, L A; Fant, B; Guercio, L A; Arreola, A C; Schmidt, H D; Sidoli, S; Han, Y; Garcia, B A; Pierce, R C

    2017-11-01

    Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny. Increased Dao1 transcription was associated with enrichment of permissive epigenetic marks on histone proteins in the hippocampus of male cocaine-sired progeny, some of which were enhanced near the Dao1 locus. Finally, hippocampal administration of d-serine reversed both the memory formation and synaptic plasticity deficits. Collectively, these results demonstrate that paternal cocaine exposure produces epigenetic remodeling in the hippocampus leading to NMDA receptor-dependent memory formation and synaptic plasticity impairments only in male progeny, which has significant implications for the male descendants of chronic cocaine users.

  14. File list: ALL.Bld.10.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: ALL.Bld.50.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: ALL.Bld.05.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Naive_T_cells hg19 All antigens Blood Naive T cells SRX1425808,SRX...1425815,SRX1425816,SRX1425814 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.Naive_T_cells.bed ...

  17. Methyltransferases mediate cell memory of a genotoxic insult.

    Science.gov (United States)

    Rugo, R E; Mutamba, J T; Mohan, K N; Yee, T; Chaillet, J R; Greenberger, J S; Engelward, B P

    2011-02-10

    Characterization of the direct effects of DNA-damaging agents shows how DNA lesions lead to specific mutations. Yet, serum from Hiroshima survivors, Chernobyl liquidators and radiotherapy patients can induce a clastogenic effect on naive cells, showing indirect induction of genomic instability that persists years after exposure. Such indirect effects are not restricted to ionizing radiation, as chemical genotoxins also induce heritable and transmissible genomic instability phenotypes. Although such indirect induction of genomic instability is well described, the underlying mechanism has remained enigmatic. Here, we show that mouse embryonic stem cells exposed to γ-radiation bear the effects of the insult for weeks. Specifically, conditioned media from the progeny of exposed cells can induce DNA damage and homologous recombination in naive cells. Notably, cells exposed to conditioned media also elicit a genome-destabilizing effect on their neighbouring cells, thus demonstrating transmission of genomic instability. Moreover, we show that the underlying basis for the memory of an insult is completely dependent on two of the major DNA cytosine methyltransferases, Dnmt1 and Dnmt3a. Targeted disruption of these genes in exposed cells completely eliminates transmission of genomic instability. Furthermore, transient inactivation of Dnmt1, using a tet-suppressible allele, clears the memory of the insult, thus protecting neighbouring cells from indirect induction of genomic instability. We have thus demonstrated that a single exposure can lead to long-term, genome-destabilizing effects that spread from cell to cell, and we provide a specific molecular mechanism for these persistent bystander effects. Collectively, our results impact the current understanding of risks from toxin exposures and suggest modes of intervention for suppressing genomic instability in people exposed to carcinogenic genotoxins.

  18. CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells

    Science.gov (United States)

    Zhang, Xiaolong; Chang Li, Xian; Xiao, Xiang; Sun, Rui; Tian, Zhigang; Wei, Haiming

    2013-01-01

    The peripheral Foxp3+ Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4+ T cells can be readily converted to Foxp3+ iTreg in vitro, and memory CD4+ T cells are resistant to conversion. In this study, we investigated the induction of Foxp3+ T cells from various CD4+ T-cell subsets in human peripheral blood. Though naive CD4+ T cells were readily converted to Foxp3+ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3+ T cells did not express the memory marker CD45RO as do Foxp3+ T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4+ T cells, defined as CD62L+ central memory T cells, could be induced by TGF-β to differentiate into Foxp3+ T cells. It is well known that Foxp3+ T cells derived from human CD4+CD25- T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4+CD62L+ central memory T cell-derived Foxp3+ T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4+ T cell-derived Foxp3+ T cells. But further research showed that mouse CD4+ central memory T cells also could be induced to differentiate into Foxp3+ T cells, such Foxp3+ T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4+CD62L+ central memory T cells as a novel potential source of iTreg. PMID:24155942

  19. Sleep enhances false memories depending on general memory performance.

    Science.gov (United States)

    Diekelmann, Susanne; Born, Jan; Wagner, Ullrich

    2010-04-02

    Memory is subject to dynamic changes, sometimes giving rise to the formation of false memories due to biased processes of consolidation or retrieval. Sleep is known to benefit memory consolidation through an active reorganization of representations whereas acute sleep deprivation impairs retrieval functions. Here, we investigated whether sleep after learning and sleep deprivation at retrieval enhance the generation of false memories in a free recall test. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal", etc.), lacking the strongest common associate or theme word (here: "black"). Free recall was tested after 9h following a night of sleep, a night of wakefulness (sleep deprivation) or daytime wakefulness. Compared with memory performance after a retention period of daytime wakefulness, both post-learning nocturnal sleep as well as acute sleep deprivation at retrieval significantly enhanced false recall of theme words. However, these effects were only observed in subjects with low general memory performance. These data point to two different ways in which sleep affects false memory generation through semantic generalization: one acts during consolidation on the memory trace per se, presumably by active reorganization of the trace in the post-learning sleep period. The other is related to the recovery function of sleep and affects cognitive control processes of retrieval. Both effects are unmasked when the material is relatively weakly encoded. Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.

  20. Memory for past public events depends on retrieval frequency but not memory age in Alzheimer's disease.

    Science.gov (United States)

    Müller, Stephan; Mychajliw, Christian; Hautzinger, Martin; Fallgatter, Andreas J; Saur, Ralf; Leyhe, Thomas

    2014-01-01

    Alzheimer's disease (AD) is characterized by retrograde memory deficits primarily caused by dysfunction of the hippocampal complex. Unresolved questions exist concerning the time course of hippocampal involvement in conscious recollection of declarative knowledge, as reports of temporal gradients of retrograde amnesia have been inconclusive. The aim of this study was to examine whether the extent and severity of retrograde amnesia is mediated by retrieval frequency or, in contrast, whether it depends on the age of the memory according to the assumptions of the main current theories of memory formation. We compared recall of past public events in patients with AD and healthy control (HC) individuals using the Historic Events Test (HET). The HET assesses knowledge about famous public events of the past 60 years divided into four time segments and consists of subjective memory rating, dating accuracy, and contextual memory tasks. Although memory for public events was impaired in AD patients, there was a strong effect of retrieval frequency across all time segments and both groups. As AD and HC groups derived similar benefits from greater retrieval frequency, cortical structures other than the hippocampal complex may mediate memory retrieval. These findings suggest that more frequently retrieved events and facts become more independent of the hippocampal complex and thus better protected against early damage of AD. This could explain why cognitive activity may delay the onset of memory decline in persons who develop AD.

  1. PERBANDINGAN JARINGAN SYARAF TIRUAN DAN NAIVE BAYES DALAM DETEKSI SESEORANG TERKENA PENYAKIT STROKE

    Directory of Open Access Journals (Sweden)

    I. Rohmana

    2015-07-01

    Full Text Available Tujuan penelitian ini adalah membuat aplikasi Jaringan Syaraf Tiruan dan Naive Bayes untuk memprediksi penyakit stroke dan membandingkan tingkat akuratan dari kedua metode yang digunakan. Sebuah aplikasi software MATLAB diciptakan untuk mendeteksi seseorang Suspect stroke.  Metode yang baik dalam mesin pembelajaran berdasarkan data training adalah Jaringan Syaraf Tiruan dan Naive Bayes, variabel data faktor gejala penyakit stroke digunakan sebagai data training dalam proses pembelajaran dari sistem yang dibuat menentukan prediksi penyakit stroke. Dari 120 data percobaan yang dilakukan, akan dihitung akurasi hasil kerja sistem yang dibagi menjadi data pelatihan dan data pengujian. Diperoleh persentase hasil kerja sistem yaitu Jaringan Syaraf Tiruan sebesar 71,11 persen, sedangkan Naive Bayes sebesar 80,55 persen. Naive Bayes lebih akurat daripada Jaringan Syaraf Tiruan dalam hal pengambilan keputusan data baru namun Jaringan Syaraf Tiruan memiliki teknik yang lebih bagus dibandingkan dengan Naive Bayes. Jaringan Syaraf Tiruan mempunyai karakteristik belajar dari data sebelumnya.The purpose of this research are make application system of Artificial Neural Network and Naive Bayes to predict stroke  and to compare the accuration between of  both methods. An application applying MATLAB software has been invented to detect a stroke suspect. A good method in learning machine based on the training data is Artificial Neural Network and Naive Bayes method, by using the data variable of some common stroke symptoms used as the training data in the learning process of the system which is going to be built to determine whether prediction of stroke disease. From 120 experiments data which had been done, will be counted the accuracy of the system which divided into some training data and the other experiment data. Retrieved the percentage of  accuracy system, The Artificial Neural Network is 71,11 percent whereas Naive Bayes is 80,555 percent. Naive Bayes

  2. TEXT CLASSIFICATION USING NAIVE BAYES UPDATEABLE ALGORITHM IN SBMPTN TEST QUESTIONS

    Directory of Open Access Journals (Sweden)

    Ristu Saptono

    2017-01-01

    Full Text Available Document classification is a growing interest in the research of text mining. Classification can be done based on the topics, languages, and so on. This study was conducted to determine how Naive Bayes Updateable performs in classifying the SBMPTN exam questions based on its theme. Increment model of one classification algorithm often used in text classification Naive Bayes classifier has the ability to learn from new data introduces with the system even after the classifier has been produced with the existing data. Naive Bayes Classifier classifies the exam questions based on the theme of the field of study by analyzing keywords that appear on the exam questions. One of feature selection method DF-Thresholding is implemented for improving the classification performance. Evaluation of the classification with Naive Bayes classifier algorithm produces 84,61% accuracy.

  3. Naive Juveniles Are More Likely to Become Breeders after Witnessing Predator Mobbing.

    Science.gov (United States)

    Griesser, Michael; Suzuki, Toshitaka N

    2017-01-01

    Responding appropriately during the first predatory attack in life is often critical for survival. In many social species, naive juveniles acquire this skill from conspecifics, but its fitness consequences remain virtually unknown. Here we experimentally demonstrate how naive juvenile Siberian jays (Perisoreus infaustus) derive a long-term fitness benefit from witnessing knowledgeable adults mobbing their principal predator, the goshawk (Accipiter gentilis). Siberian jays live in family groups of two to six individuals that also can include unrelated nonbreeders. Field observations showed that Siberian jays encounter predators only rarely, and, indeed, naive juveniles do not respond to predator models when on their own but do when observing other individuals mobbing them. Predator exposure experiments demonstrated that naive juveniles had a substantially higher first-winter survival after observing knowledgeable group members mobbing a goshawk model, increasing their likelihood of acquiring a breeding position later in life. Previous research showed that naive individuals may learn from others how to respond to predators, care for offspring, or choose mates, generally assuming that social learning has long-term fitness consequences without empirical evidence. Our results demonstrate a long-term fitness benefit of vertical social learning for naive individuals in the wild, emphasizing its evolutionary importance in animals, including humans.

  4. Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

    Science.gov (United States)

    Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-04-17

    Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

  5. Autobiographical Memory Performance in Alzheimer's Disease Depends on Retrieval Frequency.

    Science.gov (United States)

    Müller, Stephan; Mychajliw, Christian; Reichert, Carolin; Melcher, Tobias; Leyhe, Thomas

    2016-04-18

    Alzheimer's disease (AD) is characterized by memory disturbances primarily caused by pathogenic mechanisms affecting medial temporal lobe structures. As proposed by current theories of memory formation, this decrease is mediated by the age of the acquired knowledge. However, they cannot fully explain specific patterns of retrograde amnesia in AD. In the current study we examined an alternative approach and investigated whether the extent and severity of retrograde amnesia in AD is mediated by the frequency of memory retrieval or whether it depends on the mere age of knowledge. We compared recall of autobiographical incidents from three life periods in patients with amnestic mild cognitive impairment (aMCI), patients with early dementia of Alzheimer type (eDAT), and healthy control (HC) individuals using the Autobiographical Memory Interview. Retrieval frequency was operationalized by a paired comparison analysis. In contrast to HC individuals, recall of autobiographical incidents was impaired in patients with aMCI and eDAT following Ribot's gradient, with a reduced memory loss for remote compared to more recent life events. However, there was a strong effect of retrieval frequency on memory performance with frequently retrieved incidents memorized in more detail than less frequently retrieved episodes. Remote memories were recalled more often than recent ones. These findings suggest that more frequently retrieved autobiographical memories generally become more independent of the hippocampal complex and might thus be better protected against early hippocampal damage related to AD. Hence, the extent of retrograde amnesia in AD appears mainly mediated by the frequency of memory retrieval, which could plausibly explain why cognitive activity can effectively delay the onset of memory decline in AD.

  6. Olfactory Context-Dependent Memory and the Effects of Affective Congruency.

    Science.gov (United States)

    Hackländer, Ryan P M; Bermeitinger, Christina

    2017-10-31

    Odors have been claimed to be particularly effective mnemonic cues, possibly because of the strong links between olfaction and emotion processing. Indeed, past research has shown that odors can bias processing towards affectively congruent material. In order to determine whether this processing bias translates to memory, we conducted 2 olfactory-enhanced-context memory experiments where we manipulated affective congruency between the olfactory context and to-be-remembered material. Given the presumed importance of valence to olfactory perception, we hypothesized that memory would be best for affectively congruent material in the olfactory enhanced context groups. Across the 2 experiments, groups which encoded and retrieved material in the presence of an odorant exhibited better memory performance than groups that did not have the added olfactory context during encoding and retrieval. While context-enhanced memory was exhibited in the presence of both pleasant and unpleasant odors, there was no indication that memory was dependent on affective congruency between the olfactory context and the to-be-remembered material. While the results provide further support for the notion that odors can act as powerful contextual mnemonic cues, they call into question the notion that affective congruency between context and focal material is important for later memory performance. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Normal aging affects movement execution but not visual motion working memory and decision-making delay during cue-dependent memory-based smooth-pursuit.

    Science.gov (United States)

    Fukushima, Kikuro; Barnes, Graham R; Ito, Norie; Olley, Peter M; Warabi, Tateo

    2014-07-01

    Aging affects virtually all functions including sensory/motor and cognitive activities. While retinal image motion is the primary input for smooth-pursuit, its efficiency/accuracy depends on cognitive processes. Elderly subjects exhibit gain decrease during initial and steady-state pursuit, but reports on latencies are conflicting. Using a cue-dependent memory-based smooth-pursuit task, we identified important extra-retinal mechanisms for initial pursuit in young adults including cue information priming and extra-retinal drive components (Ito et al. in Exp Brain Res 229:23-35, 2013). We examined aging effects on parameters for smooth-pursuit using the same tasks. Elderly subjects were tested during three task conditions as previously described: memory-based pursuit, simple ramp-pursuit just to follow motion of a single spot, and popping-out of the correct spot during memory-based pursuit to enhance retinal image motion. Simple ramp-pursuit was used as a task that did not require visual motion working memory. To clarify aging effects, we then compared the results with the previous young subject data. During memory-based pursuit, elderly subjects exhibited normal working memory of cue information. Most movement-parameters including pursuit latencies differed significantly between memory-based pursuit and simple ramp-pursuit and also between young and elderly subjects. Popping-out of the correct spot motion was ineffective for enhancing initial pursuit in elderly subjects. However, the latency difference between memory-based pursuit and simple ramp-pursuit in individual subjects, which includes decision-making delay in the memory task, was similar between the two groups. Our results suggest that smooth-pursuit latencies depend on task conditions and that, although the extra-retinal mechanisms were functional for initial pursuit in elderly subjects, they were less effective.

  8. File list: InP.Bld.50.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Naive_T_cells hg19 Input control Blood Naive T cells SRX1425815,SR...X1425816,SRX1425814 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.50.AllAg.Naive_T_cells.bed ...

  9. Naive Theories of Social Groups

    Science.gov (United States)

    Rhodes, Marjorie

    2012-01-01

    Four studies examined children's (ages 3-10, Total N = 235) naive theories of social groups, in particular, their expectations about how group memberships constrain social interactions. After introduction to novel groups of people, preschoolers (ages 3-5) reliably expected agents from one group to harm members of the other group (rather than…

  10. Subtrochanteric fractures in bisphosphonate-naive patients

    DEFF Research Database (Denmark)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven

    2011-01-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained ...

  11. Dual-memory processes in crack cocaine dependents: The effects of childhood neglect on recall.

    Science.gov (United States)

    Tractenberg, Saulo G; Viola, Thiago W; Gomes, Carlos F A; Wearick-Silva, Luis Eduardo; Kristensen, Christian H; Stein, Lilian M; Grassi-Oliveira, Rodrigo

    2015-01-01

    Exposure to adversities during sensitive periods of neurodevelopment is associated with the subsequent development of substance dependence and exerts harmful, long-lasting effects upon memory functioning. In this study, we investigated the relationship between childhood neglect (CN) and memory using a dual-process model that quantifies recollective and non-recollective retrieval processes in crack cocaine dependents. Eighty-four female crack cocaine-dependent inpatients who did (N = 32) or did not (N = 52) report a history of CN received multiple opportunities to study and recall a short list composed of familiar and concrete words and then received a delayed-recall test. Crack cocaine dependents with a history of CN showed worse performance on free-recall tests than did dependents without a history of CN; this finding was associated with declines in recollective retrieval (direct access) rather than non-recollective retrieval. In addition, we found no evidence of group differences in forgetting rates between immediate- and delayed-recall tests. The results support developmental models of traumatology and suggest that neglect of crack cocaine dependents in early life disrupts the adult memory processes that support the retrieval of detailed representations of events from the past.

  12. Cancer immunotherapy and immunological memory.

    Science.gov (United States)

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

    Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

  13. Resistance exercise improves hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    R.C. Cassilhas

    2012-12-01

    Full Text Available It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R, which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group: control, SHAM, and resistance exercise (RES. The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA, the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05. Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

  14. 636 ART-naive patients were enrolled; 361 completed 6 months of ...

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. 636 ART-naive patients were enrolled; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care). 636 ART-naive patients were enrolled; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care).

  15. Correlated electron dynamics and memory in time-dependent density functional theory

    International Nuclear Information System (INIS)

    Thiele, Mark

    2009-01-01

    Time-dependent density functional theory (TDDFT) is an exact reformulation of the time-dependent many-electron Schroedinger equation, where the problem of many interacting electrons is mapped onto the Kohn-Sham system of noninteracting particles which reproduces the exact electronic density. In the Kohn-Sham system all non-classical many-body effects are incorporated in the exchange-correlation potential which is in general unknown and needs to be approximated. It is the goal of this thesis to investigate the connection between memory effects and correlated electron dynamics in strong and weak fields. To this end one-dimensional two-electron singlet systems are studied. At the same time these systems include the onedimensional helium atom model, which is an established system to investigate the crucial effects of correlated electron dynamics in external fields. The studies presented in this thesis show that memory effects are negligible for typical strong field processes. Here the approximation of the spatial nonlocality is of primary importance. For the photoabsorption spectra on the other hand the neglect of memory effects leads to qualitative and quantitative errors, which are shown to be connected to transitions of double excitation character. To develop a better understanding of the conditions under which memory effects become important quantum fluid dynamics has been found to be especially suitable. It represents a further exact reformulation of the quantum mechanic many-body problem which is based on hydrodynamic quantities such as density and velocity. Memory effects are shown to be important whenever the velocity field develops strong gradients and dissipative effects contribute. (orig.)

  16. Correlated electron dynamics and memory in time-dependent density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Thiele, Mark

    2009-07-28

    Time-dependent density functional theory (TDDFT) is an exact reformulation of the time-dependent many-electron Schroedinger equation, where the problem of many interacting electrons is mapped onto the Kohn-Sham system of noninteracting particles which reproduces the exact electronic density. In the Kohn-Sham system all non-classical many-body effects are incorporated in the exchange-correlation potential which is in general unknown and needs to be approximated. It is the goal of this thesis to investigate the connection between memory effects and correlated electron dynamics in strong and weak fields. To this end one-dimensional two-electron singlet systems are studied. At the same time these systems include the onedimensional helium atom model, which is an established system to investigate the crucial effects of correlated electron dynamics in external fields. The studies presented in this thesis show that memory effects are negligible for typical strong field processes. Here the approximation of the spatial nonlocality is of primary importance. For the photoabsorption spectra on the other hand the neglect of memory effects leads to qualitative and quantitative errors, which are shown to be connected to transitions of double excitation character. To develop a better understanding of the conditions under which memory effects become important quantum fluid dynamics has been found to be especially suitable. It represents a further exact reformulation of the quantum mechanic many-body problem which is based on hydrodynamic quantities such as density and velocity. Memory effects are shown to be important whenever the velocity field develops strong gradients and dissipative effects contribute. (orig.)

  17. PENERAPAN NAIVE BAYES PADA INTRUSION DETECTION SYSTEM DENGAN DISKRITISASI VARIABEL

    Directory of Open Access Journals (Sweden)

    I Nyoman Trisna Wirawan

    2015-07-01

    Pada penelitian ini akan dibahas mengenai penerapan naive bayes classifier dengan menggunakan pemilihan atribut berdasarkan pada korelasi serta preprocessing data dengan diskritisasi dengan menggunakan metode mean/standar deviasi untuk atribut kontinu dengan menggunakan 3-interval dan 5-interval. Hasil percobaan menunjukan bahwa penerapan naive bayes pada klasifikasi data yang telah melewati proses diskritisasi mampu memberikan akurasi hingga 89% dengan running time rata-rata adalah 31 detik.

  18. Dreaming of a Learning Task Is Associated with Enhanced Sleep-Dependent Memory Consolidation

    OpenAIRE

    Wamsley, Erin J.; Tucker, Matthew; Payne, Jessica D.; Benavides, Joseph A.; Stickgold, Robert

    2010-01-01

    It is now well established that post-learning sleep is beneficial for human memory performance [1–5]. Meanwhile, human and animal studies demonstrate that learning-related neural activity is re-expressed during post-training non-rapid eye movement sleep (NREM) [6–9]. NREM sleep processes appear to be particularly beneficial for hippocampus-dependent forms of memory [1–3, 10]. These observations suggest that learning triggers the reactivation and reorganization of memory traces during sleep, a...

  19. Witness memory and alcohol: The effects of state-dependent recall.

    Science.gov (United States)

    Schreiber Compo, Nadja; Carol, Rolando N; Evans, Jacqueline R; Pimentel, Pamela; Holness, Howard; Nichols-Lopez, Kristin; Rose, Stefan; Furton, Kenneth G

    2017-04-01

    Many real-world eyewitnesses are under the influence of alcohol either at the time of the crime, the interview, or both. Only recently has empirical research begun to examine the effects of alcohol on witness memory, yielding mixed results. The present study tested the importance of state-dependent memory in the context of alcohol's effects on encoding versus retrieval of a witnessed event, while simultaneously informing real-world investigative practices: Should witnesses sober up before an interview? Participants (N = 249) were randomized to a control, placebo, or alcohol condition at encoding and to either an immediate retrieval condition (in the same state) or a 1-week delay control, placebo, or alcohol retrieval condition. They recalled a witnessed mock crime using open ended and cued recall formats. After a delay, witnesses intoxicated at both encoding and retrieval provided less accurate information than witnesses in sober or placebo groups at both times. There was no advantage of state-dependent memory but intoxicated witnesses were best when recalling immediately compared to 1 week later (sober, placebo, or reintoxicated). Findings have direct implications for the timing of intoxicated witnesses' interviews such that moderately intoxicated witnesses may not benefit from a sobering delay but rather, should be interviewed immediately. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Chewing gum and context-dependent memory: the independent roles of chewing gum and mint flavour.

    Science.gov (United States)

    Johnson, Andrew J; Miles, Christopher

    2008-05-01

    Two experiments independently investigated the basis of the chewing gum induced context-dependent memory effect. At learning and/or recall, participants either chewed flavourless gum (Experiment 1) or received mint-flavoured strips (Experiment 2). No context-dependent memory effect was found with either flavourless gum or mint-flavoured strips, indicating that independently the contexts were insufficiently salient to induce the effect. This is found despite participants' subjective ratings indicating a perceived change in state following administration of flavourless gum or mint-flavoured strips. Additionally, some preliminary evidence for a non-additive facilitative effect of receiving gum or flavour at either learning and/or recall is reported. The findings raise further concerns regarding the robustness of the previously reported context-dependent memory effect with chewing gum.

  1. Functional compensation in the ventromedial prefrontal cortex improves memory-dependent decisions in older adults.

    Science.gov (United States)

    Lighthall, Nichole R; Huettel, Scott A; Cabeza, Roberto

    2014-11-19

    Everyday consumer choices frequently involve memory, as when we retrieve information about consumer products when making purchasing decisions. In this context, poor memory may affect decision quality, particularly in individuals with memory decline, such as older adults. However, age differences in choice behavior may be reduced if older adults can recruit additional neural resources that support task performance. Although such functional compensation is well documented in other cognitive domains, it is presently unclear whether it can support memory-guided decision making and, if so, which brain regions play a role in compensation. The current study engaged younger and older humans in a memory-dependent choice task in which pairs of consumer products from a popular online-shopping site were evaluated with different delays between the first and second product. Using functional imaging (fMRI), we found that the ventromedial prefrontal cortex (vmPFC) supports compensation as defined by three a priori criteria: (1) increased vmPFC activation was observed in older versus younger adults; (2) age-related increases in vmPFC activity were associated with increased retrieval demands; and (3) increased vmPFC activity was positively associated with performance in older adults-evidence of successful compensation. Extending these results, we observed evidence for compensation in connectivity between vmPFC and the dorsolateral PFC during memory-dependent choice. In contrast, we found no evidence for age differences in value-related processing or age-related compensation for choices without delayed retrieval. Together, these results converge on the conclusion that age-related decline in memory-dependent choice performance can be minimized via functional compensation in vmPFC. Copyright © 2014 the authors 0270-6474/14/3415648-10$15.00/0.

  2. Context-dependent utility overrides absolute memory as a determinant of choice

    OpenAIRE

    Pompilio, Lorena; Kacelnik, Alex

    2009-01-01

    A core problem of decision theories is that although decisionmakers’ preferences depend on learning, their choices could be driven either by learned representations of the physical properties of each alternative (for instance reward sizes) or of the benefit (utility and fitness) experienced from them. Physical properties are independent of the subject’s state and context, but utility depends on both. We show that starlings’ choices are better explained by memory for context-dependent utility ...

  3. Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory.

    Science.gov (United States)

    Sultan, S; Mandairon, N; Kermen, F; Garcia, S; Sacquet, J; Didier, A

    2010-07-01

    Inhibitory interneurons of the olfactory bulb are subjected to permanent adult neurogenesis. Their number is modulated by learning, suggesting that they could play a role in plastic changes of the bulbar network associated with olfactory memory. Adult male C57BL/6 mice were trained in an associative olfactory task, and we analyzed long-term retention of the task 5, 30, and 90 d post-training. In parallel, we assessed the fate of these newborn cells, mapped their distribution in the olfactory bulb and measured their functional implication using the immediate early gene Zif268. In a second set of experiments, we pharmacologically modulated glutamatergic transmission and using the same behavioral task assessed the consequences on memory retention and neurogenesis. Finally, by local infusion of an antimitotic drug, we selectively blocked neurogenesis during acquisition of the task and looked at the effects on memory retention. First we demonstrated that retrieval of an associative olfactory task recruits the newborn neurons in odor-specific areas of the olfactory bulb selected to survive during acquisition of the task and that it does this in a manner that depends on the strength of learning. We then demonstrated that acquisition is not dependent on neurogenesis if long-term retention of the task is abolished by blocking neurogenesis. Adult-born neurons are thus involved in changes in the neural representation of an odor; this underlies long-term olfactory memory as the strength of learning is linked to the duration of this memory. Neurogenesis thus plays a crucial role in long-term olfactory memory.

  4. Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors

    Science.gov (United States)

    Beckhove, Philipp; Feuerer, Markus; Dolenc, Mathias; Schuetz, Florian; Choi, Carmen; Sommerfeldt, Nora; Schwendemann, Jochen; Ehlert, Katrin; Altevogt, Peter; Bastert, Gunther; Schirrmacher, Volker; Umansky, Viktor

    2004-01-01

    Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA– memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells. PMID:15232613

  5. Ensemble coding of context-dependent fear memory in the amygdala

    OpenAIRE

    Orsini, Caitlin A.; Yan, Chen; Maren, Stephen

    2013-01-01

    After fear conditioning, presenting the conditioned stimulus (CS) alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellula...

  6. Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction.

    Science.gov (United States)

    Quednow, Boris B; Jessen, Frank; Kuhn, Kai-Uwe; Maier, Wolfgang; Daum, Irene; Wagner, Michael

    2006-05-01

    Chronic administration of the common club drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is associated with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains of rodents and non-human primates, and evidence suggests that recreational MDMA consumption may also affect the human serotonergic system. Moreover, it was consistently shown that abstinent MDMA users have memory deficits. Recently, it was supposed that these deficits are an expression of a temporal or rather hippocampal dysfunction caused by the serotonergic neurotoxicity of MDMA. The aim of this study is to examine the memory deficits of MDMA users neuropsychologically in order to evaluate the role of different brain regions. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users and 19 male drug-naive control subjects were examined with a German version of the Rey Auditory Verbal Learning Test (RAVLT). MDMA users showed widespread and marked verbal memory deficits, compared to drug-naive controls as well as compared to cannabis users, whereas cannabis users did not differ from control subjects in their memory performance. MDMA users revealed impairments in learning, consolidation, recall and recognition. In addition, they also showed a worse recall consistency and strong retroactive interference whereby both measures were previously associated with frontal lobe function. There was a significant correlation between memory performance and the amount of MDMA taken. These results suggest that the memory deficits of MDMA users are not only the result of a temporal or hippocampal dysfunction, but also of a dysfunction of regions within the frontal cortex.

  7. Long memory and tail dependence in trading volume and volatility

    DEFF Research Database (Denmark)

    Rossi, Eduardo; Santucci de Magistris, Paolo

    2013-01-01

    We investigate the relationship between volatility, measured by realized volatility, and trading volume for 25 NYSE stocks. We show that volume and volatility are long memory but not fractionally cointegrated in most cases. We also find right tail dependence in the volatility and volume innovations...

  8. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    Adriana eBarman

    2014-04-01

    Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

  9. General and Local: Averaged k-Dependence Bayesian Classifiers

    Directory of Open Access Journals (Sweden)

    Limin Wang

    2015-06-01

    Full Text Available The inference of a general Bayesian network has been shown to be an NP-hard problem, even for approximate solutions. Although k-dependence Bayesian (KDB classifier can construct at arbitrary points (values of k along the attribute dependence spectrum, it cannot identify the changes of interdependencies when attributes take different values. Local KDB, which learns in the framework of KDB, is proposed in this study to describe the local dependencies implicated in each test instance. Based on the analysis of functional dependencies, substitution-elimination resolution, a new type of semi-naive Bayesian operation, is proposed to substitute or eliminate generalization to achieve accurate estimation of conditional probability distribution while reducing computational complexity. The final classifier, averaged k-dependence Bayesian (AKDB classifiers, will average the output of KDB and local KDB. Experimental results on the repository of machine learning databases from the University of California Irvine (UCI showed that AKDB has significant advantages in zero-one loss and bias relative to naive Bayes (NB, tree augmented naive Bayes (TAN, Averaged one-dependence estimators (AODE, and KDB. Moreover, KDB and local KDB show mutually complementary characteristics with respect to variance.

  10. Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

    Science.gov (United States)

    Wagner, Isabella C; van Buuren, Mariët; Bovy, Leonore; Morris, Richard G; Fernández, Guillén

    2017-02-01

    Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

  11. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    Directory of Open Access Journals (Sweden)

    Charlotte Rachael Flavell

    2013-12-01

    Full Text Available The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of a memory following it’s reactivation and/or extinction, and investigates the evidence that extinction may involve both new learning as well as a partial destabilization-induced erasure of the original memory trace.

  12. When memory is not enough: Electrophysiological evidence for goal-dependent use of working memory representations in guiding visual attention

    Science.gov (United States)

    Carlisle, Nancy B.; Woodman, Geoffrey F.

    2014-01-01

    Biased competition theory proposes that representations in working memory drive visual attention to select similar inputs. However, behavioral tests of this hypothesis have led to mixed results. These inconsistent findings could be due to the inability of behavioral measures to reliably detect the early, automatic effects on attentional deployment that the memory representations exert. Alternatively, executive mechanisms may govern how working memory representations influence attention based on higher-level goals. In the present study, we tested these hypotheses using the N2pc component of participants’ event-related potentials (ERPs) to directly measure the early deployments of covert attention. Participants searched for a target in an array that sometimes contained a memory-matching distractor. In Experiments 1–3, we manipulated the difficulty of the target discrimination and the proximity of distractors, but consistently observed that covert attention was deployed to the search targets and not the memory-matching distractors. In Experiment 4, we showed that when participants’ goal involved attending to memory-matching items that these items elicited a large and early N2pc. Our findings demonstrate that working memory representations alone are not sufficient to guide early deployments of visual attention to matching inputs and that goal-dependent executive control mediates the interactions between working memory representations and visual attention. PMID:21254796

  13. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

    Science.gov (United States)

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-05-01

    Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

  14. Chewing gum and context-dependent memory: The independent roles of chewing gum and mint flavour

    OpenAIRE

    Johnson, A.J.; Miles, C.

    2008-01-01

    Two experiments independently investigated the basis of the chewing-gum induced context-dependent memory effect (Baker et al, 2004). At learning and/or recall participants either chewed flavourless gum (Experiment 1) or received mint-flavoured strips (Experiment 2). No context dependent memory effect was found with either flavourless gum or mint-flavoured strips, indicating that independently the contexts were insufficiently salient to induce the effect. This is found despite participants’ su...

  15. Macular Carotenoids, Aerobic Fitness, and Central Adiposity Are Associated Differentially with Hippocampal-Dependent Relational Memory in Preadolescent Children.

    Science.gov (United States)

    Hassevoort, Kelsey M; Khazoum, Sarah E; Walker, John A; Barnett, Sasha M; Raine, Lauren B; Hammond, Billy R; Renzi-Hammond, Lisa M; Kramer, Arthur F; Khan, Naiman A; Hillman, Charles H; Cohen, Neal J

    2017-04-01

    To examine the associations of macular pigment carotenoids (lutein, meso-zeaxanthin, and zeaxanthin), aerobic fitness, and central adiposity with hippocampal-dependent relational memory in prepubescent children. Children between 7 and 10 years of age (n = 40) completed a task designed to assess relational memory performance and participated in aerobic fitness, adiposity, and macular pigment optical density (MPOD) assessment. Aerobic fitness was assessed via a modified Balke treadmill protocol designed to measure maximal oxygen volume. Central adiposity was assessed via dual-energy x-ray absorptiometry. MPOD was measured psychophysically by the use of customized heterochromatic flicker photometry. Statistical analyses included correlations and hierarchical linear regression. Aerobic fitness and MPOD were associated negatively with relational memory errors (P memory errors (P memory performance even after we accounted for aerobic fitness (β = -0.388, P = .007). Even after we adjusted for aerobic fitness and central adiposity, factors known to relate to hippocampal-dependent memory, MPOD positively and significantly predicted hippocampal-dependent memory performance. ClinicalTrials.gov: NCT01619826. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Reduced error signalling in medication-naive children with ADHD

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Allen, Elena A; Eichele, Heike

    2016-01-01

    BACKGROUND: We examined the blood-oxygen level-dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We acquired...... functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8-12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions...... and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations. RESULTS: We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions...

  17. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

    Directory of Open Access Journals (Sweden)

    Shih-pi Ku

    2017-07-01

    Full Text Available The subiculum and the lateral entorhinal cortex (LEC are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1 receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum, both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors. This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

  18. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex.

    Science.gov (United States)

    Ku, Shih-Pi; Nakamura, Nozomu H; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M

    2017-01-01

    The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc , which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

  19. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

    Science.gov (United States)

    Ku, Shih-pi; Nakamura, Nozomu H.; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M.

    2017-01-01

    The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval. PMID:28790897

  20. Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory.

    Science.gov (United States)

    Alaghband, Yasaman; O'Dell, Steven J; Azarnia, Siavash; Khalaj, Anna J; Guzowski, John F; Marshall, John F

    2014-12-01

    The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal-associated (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine

  1. Activity dependent protein degradation is critical for the formation and stability of fear memory in the amygdala.

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

    Full Text Available Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses.

  2. Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

    OpenAIRE

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

    2011-01-01

    It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memo...

  3. Profile of Executive and Memory Function Associated with Amphetamine and Opiate Dependence

    Science.gov (United States)

    Ersche, Karen D; Clark, Luke; London, Mervyn; Robbins, Trevor W; Sahakian, Barbara J

    2007-01-01

    Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices. PMID:16160707

  4. A Naive-Bayes classifier for damage detection in engineering materials

    Energy Technology Data Exchange (ETDEWEB)

    Addin, O. [Laboratory of Intelligent Systems, Institute of Advanced Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Sapuan, S.M. [Department of Mechanical and Manufacturing Engineering, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia)]. E-mail: sapuan@eng.upm.edu.my; Mahdi, E. [Department of Aerospace Engineering, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Othman, M. [Department of Communication Technology and Networks, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia)

    2007-07-01

    This paper is intended to introduce the Bayesian network in general and the Naive-Bayes classifier in particular as one of the most successful classification systems to simulate damage detection in engineering materials. A method for feature subset selection has also been introduced too. The method is based on mean and maximum values of the amplitudes of waves after dividing them into folds then grouping them by a clustering algorithm (e.g. k-means algorithm). The Naive-Bayes classifier and the feature sub-set selection method were analyzed and tested on two sets of data. The data sets were conducted based on artificial damages created in quasi isotopic laminated composites of the AS4/3501-6 graphite/epoxy system and ball bearing of the type 6204 with a steel cage. The Naive-Bayes classifier and the proposed feature subset selection algorithm have been shown as efficient techniques for damage detection in engineering materials.

  5. Blocking the eIF2α kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory.

    Science.gov (United States)

    Stern, Elad; Chinnakkaruppan, Adaikkan; David, Orit; Sonenberg, Nahum; Rosenblum, Kobi

    2013-02-06

    Age-associated memory deterioration (and the decline in ability to acquire new information) is one of the major diseases of our era. Cognitive enhancement can be achieved by using psycho-stimulants, such as caffeine or nicotine, but very little is known about drugs that can enhance the consolidation phase of memories in the cortex, the brain structure considered to store, at least partially, long-term memories. We used cortex-dependent taste-learning paradigms to test the hypothesis that pharmacological manipulation of the translation initiation eIF2α, which plays a role in hippocampus-dependent memory, can enhance positive or negative forms of taste memories. We found that dephosphorylation (Ser51) of eIF2α, specifically in the cortex, is both correlated with and necessary for normal memory consolidation. To reduce eIF2α phosphorylation and improve memory consolidation, we pharmacologically inhibited one of the eIF2α kinases, PKR, which is known to be involved in brain aging and Alzheimer's disease. Systemic or local microinjection of PKR inhibitor to the gustatory cortex enhanced both positive and negative forms of taste memory in rats and mice. Our results provide clear evidence that PKR plays a major role in cortex-dependent memory consolidation and, therefore, that pharmacological inhibition of PKR is a potential target for drugs to enhance cognition.

  6. The dynamic nature of systems consolidation: Stress during learning as a switch guiding the rate of the hippocampal dependency and memory quality.

    Science.gov (United States)

    Pedraza, Lizeth K; Sierra, Rodrigo O; Boos, Flávia Z; Haubrich, Josué; Quillfeldt, Jorge A; Alvares, Lucas de Oliveira

    2016-03-01

    Memory fades over time, becoming more schematic or abstract. The loss of contextual detail in memory may reflect a time-dependent change in the brain structures supporting memory. It has been well established that contextual fear memory relies on the hippocampus for expression shortly after learning, but it becomes hippocampus-independent at a later time point, a process called systems consolidation. This time-dependent process correlates with the loss of memory precision. Here, we investigated whether training intensity predicts the gradual decay of hippocampal dependency to retrieve memory, and the quality of the contextual memory representation over time. We have found that training intensity modulates the progressive decay of hippocampal dependency and memory precision. Strong training intensity accelerates systems consolidation and memory generalization in a remarkable timeframe match. The mechanisms underpinning such process are triggered by glucocorticoid and noradrenaline released during training. These results suggest that the stress levels during emotional learning act as a switch, determining the fate of memory quality. Moderate stress will create a detailed memory, whereas a highly stressful training will develop a generic gist-like memory. © 2015 Wiley Periodicals, Inc.

  7. Chewing gum does not induce context-dependent memory when flavor is held constant.

    Science.gov (United States)

    Overman, Amy A; Sun, Justin; Golding, Abbe C; Prevost, Darius

    2009-10-01

    This study examined the effect of chewing gum on memory when flavor is held constant. Four separate groups of participants (total n=101) completed a word recall task. At learning and recall, participants either chewed a piece of gum or sucked a sweet. Each participant completed the memory task twice, once with abstract words and once with concrete words. A significant effect of word type (concrete vs. abstract) was found, however recall performance was not improved by matched oral activity at learning and recall. The results cast further doubt on the ability of chewing gum to induce context-dependent memory effects.

  8. Effect of Pentylenetetrazol on Morphine State-Dependent Memory in Rat

    Directory of Open Access Journals (Sweden)

    Marziyeh Tavassoli

    2017-09-01

    Full Text Available Abstract Background: Learning and memory are among the higher functions of the brain. State-dependent memory (STM is a type of memory in which the recall of a learned behavior is happend only in the same sensory and physiologic condition in which the behavior is encoded. The STM is seen with some drugs, e.g. the morphine. The pentylenetetrazol (PTZ is a durg which is used for the induction of seizure in experimental models. Some studies have been revealed different effects of the PTZ on brain higher function (learning, memory …. The aim of present study was to explore the effect of PTZ on morphine-induced STM. Materials and Methods: In this study, male adult Wistar rats (190-220 g were used. Animals in 3 groups (n=8 during 3 sessions (learning/memory, STM and interaction were studied. During 48 hour (training and test the learning and memory of animals were studied in inhibitory avoidance apparatus. The step-through latency in the test day was used as a criterion for memory. Post-training injection of saline or morphine (2.5, 5 and 7.5 mg/kg-ip in different groups was carried out. In addition, the pre-test injection of morphine at the same doses was made to study the STM. Moreover, the interaction of pre-test single-dose PTZ (60 mg/kg-ip on STM was studied. The locomotion of the animals was measured using the open field. Results: The post-training injection of morphine (2.5, 5 and 7.5 mg/kg-ip impaired the inhibitory memory of rats compared to control group (p<0.001. The post-training and pre-test injections of the same dose of morphine (7.5 mg/kg-ip reversed the impaired memory compared to morphine (2.5 and 5 mg/kg-ip, (p<0.001. The pre-test PTZ (60 mg/kg-ip maintained the morphine (7.5 mg/kg-ip STM (p<0.001. Conclusion: The present study revealed that the post-training ip injection of different doses of morphine results in the impairment of inhibitory avoidance memory in rat. In addition, the pre-test injection of the same doses of morphine

  9. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    Science.gov (United States)

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Acute effects of alcohol on intrusive memory development and viewpoint dependence in spatial memory support a dual representation model.

    Science.gov (United States)

    Bisby, James A; King, John A; Brewin, Chris R; Burgess, Neil; Curran, H Valerie

    2010-08-01

    A dual representation model of intrusive memory proposes that personally experienced events give rise to two types of representation: an image-based, egocentric representation based on sensory-perceptual features; and a more abstract, allocentric representation that incorporates spatiotemporal context. The model proposes that intrusions reflect involuntary reactivation of egocentric representations in the absence of a corresponding allocentric representation. We tested the model by investigating the effect of alcohol on intrusive memories and, concurrently, on egocentric and allocentric spatial memory. With a double-blind independent group design participants were administered alcohol (.4 or .8 g/kg) or placebo. A virtual environment was used to present objects and test recognition memory from the same viewpoint as presentation (tapping egocentric memory) or a shifted viewpoint (tapping allocentric memory). Participants were also exposed to a trauma video and required to detail intrusive memories for 7 days, after which explicit memory was assessed. There was a selective impairment of shifted-view recognition after the low dose of alcohol, whereas the high dose induced a global impairment in same-view and shifted-view conditions. Alcohol showed a dose-dependent inverted "U"-shaped effect on intrusions, with only the low dose increasing the number of intrusions, replicating previous work. When same-view recognition was intact, decrements in shifted-view recognition were associated with increases in intrusions. The differential effect of alcohol on intrusive memories and on same/shifted-view recognition support a dual representation model in which intrusions might reflect an imbalance between two types of memory representation. These findings highlight important clinical implications, given alcohol's involvement in real-life trauma. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Development of naive personality perception

    OpenAIRE

    Hayashi, Tomoyuki

    2004-01-01

    Lay persons usually understand that the personality has consistency and causality. They also have the knowledge of what contents the personality consists of. Research of "theories of mind," which focuses on the developmental processes of the naive understanding of mind, suggests three stages : (a) alignment of actions (imitation) fosters the foundation of social cognition in young children (i.e., understanding that the mind causes behaviors, grasping the identity of a person, and discovering ...

  12. Non-Dependent and Dependent Daily Cannabis Users Differ in Mental Health but Not Prospective Memory Ability

    Directory of Open Access Journals (Sweden)

    Ruth Braidwood

    2018-03-01

    Full Text Available Research suggests that daily cannabis users have impaired memory for past events, but it is not clear whether they are also impaired in prospective memory (PM for future events. The present study examined PM in daily cannabis users who were either dependent (n = 18 or non-dependent (n = 18, and compared them with non-using controls (n = 18. The effect of future event simulation (FES on PM performance was also examined. Participants were matched across groups on age, gender, and highest level of education. The virtual week (VW was used to objectively assess PM abilities, both at baseline and following FES. Other measures used were: cannabis use variables, immediate and delayed prose recall, phonemic and category fluency, spot-the-word test (premorbid intelligence, Beck Depression Inventory, Beck Anxiety Inventory, and a measure of schizotypy (Oxford-Liverpool Inventory of Feelings and Experiences: unusual experiences subscale. No group differences were found in PM performance on the VW, and FES did not improve PM performance in any group. Dependent cannabis users scored higher on depression, anxiety, and schizotypy than both other groups with non-dependent cannabis users scoring at a similar level to controls. There were no group differences in alcohol use. Findings suggest that when carefully matched on baseline variables, and not differing in premorbid IQ or alcohol use, young, near-daily cannabis users do not differ from non-using controls in PM performance.

  13. The Dynamics of Memory: Context-Dependent Updating

    Science.gov (United States)

    Hupbach, Almut; Hardt, Oliver; Gomez, Rebecca; Nadel, Lynn

    2008-01-01

    Understanding the dynamics of memory change is one of the current challenges facing cognitive neuroscience. Recent animal work on memory reconsolidation shows that memories can be altered long after acquisition. When reactivated, memories can be modified and require a restabilization (reconsolidation) process. We recently extended this finding to…

  14. Medial Entorhinal Cortex Lesions Only Partially Disrupt Hippocampal Place Cells and Hippocampus-Dependent Place Memory

    Directory of Open Access Journals (Sweden)

    Jena B. Hales

    2014-11-01

    Full Text Available The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory.

  15. Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

    Science.gov (United States)

    Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

    2016-01-01

    The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

  16. Context-dependent memory in two natural environments: on land and underwater

    Science.gov (United States)

    Godden, D. R.; Baddeley, A. D.

    1975-01-01

    In a free recall experiment, divers learn lists of words in two natural environments: on dry land and underwater, and recalled the words in either the environment of original learning, or in the alternative environment. A subsequent experiment related these actions to context-dependent memory. (Editor/RK)

  17. Using k-dependence causal forest to mine the most significant dependency relationships among clinical variables for thyroid disease diagnosis.

    Directory of Open Access Journals (Sweden)

    LiMin Wang

    Full Text Available Numerous data mining models have been proposed to construct computer-aided medical expert systems. Bayesian network classifiers (BNCs are more distinct and understandable than other models. To graphically describe the dependency relationships among clinical variables for thyroid disease diagnosis and ensure the rationality of the diagnosis results, the proposed k-dependence causal forest (KCF model generates a series of submodels in the framework of maximum spanning tree (MST and demonstrates stronger dependence representation. Friedman test on 12 UCI datasets shows that KCF has classification accuracy advantage over the other state-of-the-art BNCs, such as Naive Bayes, tree augmented Naive Bayes, and k-dependence Bayesian classifier. Our extensive experimental comparison on 4 medical datasets also proves the feasibility and effectiveness of KCF in terms of sensitivity and specificity.

  18. Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

    Science.gov (United States)

    Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

    2016-01-01

    Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

  19. Children and Adolescents' Understandings of Family Resemblance: A Study of Naive Inheritance Concepts

    Science.gov (United States)

    Williams, Joanne M.

    2012-01-01

    This paper aims to provide developmental data on two connected naive inheritance concepts and to explore the coherence of children's naive biology knowledge. Two tasks examined children and adolescents' (4, 7, 10, and 14 years) conceptions of phenotypic resemblance across kin (in physical characteristics, disabilities, and personality traits). The…

  20. Effects of Financial Crises on the Long Memory Volatility Dependency of Foreign Exchange Rates: the Asian Crisis vs. the Global Crisis

    Directory of Open Access Journals (Sweden)

    Young Wook Han

    2014-03-01

    Full Text Available This paper examines the effects of financial crises on the long memory volatility dependency of daily exchange returns focusing on the Asian crisis in 97-98 and the Global crisis in 08-09. By using the daily KRW-USD and JPY-USD exchange rates which have different trading regions and volumes, this paper first applies both the parametric FIGARCH model and the semi-parametric Local Whittle method to estimate the long memory volatility dependency of the daily returns and the temporally aggregated returns of the two exchange rates. Then it compares the effects of the two financial crises on the long memory volatility dependency of the daily returns. The estimation results reflect that the long memory volatility dependency of the KRW-USD is generally greater than that of the JPY-USD returns and the long memory dependency of the two returns appears to be invariant to temporal aggregation. And, the two financial crises appear to affect the volatility dynamics of all the returns by inducing greater long memory dependency in the volatility process of the exchange returns, but the degree of the effects of the two crises seems to be different on the exchange rates.

  1. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    OpenAIRE

    Flavell, Charlotte R.; Lambert, Elliot A.; Winters, Boyer D.; Bredy, Timothy W.

    2013-01-01

    The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session) can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of...

  2. Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients

    Directory of Open Access Journals (Sweden)

    Jean-Marc Hoffmann

    2018-01-01

    Full Text Available IntroductionTherapy with chimeric antigen receptor T (CART cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (TN vs. effector (TE T cells, TN cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the TN/TE ratio of CART cells.Materials and methodsCART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL-7/IL-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs and 11 patients with chronic lymphocytic leukemia (CLL for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays.ResultsIL-7/IL-15 preferentially induced differentiation into TN, stem cell memory (TSCM: naive CD27+ CD95+, CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (TEM, CD56+ and CD4+ T regulatory (TReg CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CARTN cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CARTN cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CARTN cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CARTN cells in untreated CLL patients. Final TN/TE ratio stayed <0.3 despite stimulation condition for patients

  3. The effects of heterogeneities on memory-dependent diffusion

    Science.gov (United States)

    Adib, Farhad; Neogi, P.

    1993-07-01

    Case II diffusion is often seen in glassy polymers, where the mass uptake in sorption is proportional to time t instead of sqrt{t}. A memory dependent diffusion is needed to explain such effects, where the relaxation function used to describe the memory effect has a characteristic time. The ratio of this time to the overall diffusion times is the diffusional Deborah number. Simple models show that case II results when the Deborah number is around one, that is, when the two time scales are comparable. Under investigation are the possible effects of the fact that the glassy polymers are heterogeneous over molecular scales. The averaging form given by DiMarzio and Sanchez has been used to obtain the averaged response. The calculated dynamics of sorption show that whereas case II is still observed, the long term tails change dramatically from the oscillatory to torpid, to chaotic, which are all observed in the experiments. The Deborah number defined here in a self-consistent manner collapses in those cases, but causes no other ill-effects.

  4. Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

    Science.gov (United States)

    Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

    2012-01-01

    The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

  5. The Polarity-Dependent Effects of the Bilateral Brain Stimulation on Working Memory

    Directory of Open Access Journals (Sweden)

    Fatemeh Keshvari

    2013-08-01

    Full Text Available Introduction: Working memory plays a critical role in cognitive processes which are central to our daily life. Neuroimaging studies have shown that one of the most important areas corresponding to the working memory is the dorsolateral prefrontal cortex (DLFPC. This study was aimed to assess whether bilateral modulation of the DLPFC using a noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS, modi.es the working memory function in healthy adults.Methods: In a randomized sham-controlled cross-over study, 60 subjects (30 Males received sham and active tDCS in two subgroups (anode left/cathode right and anode right/cathode left of the DLPFC. Subjects were presented working memory n-back task while the reaction time and accuracy were recorded.Results: A repeated measures, mixed design ANOVA indicated a signi.cant difference between the type of stimulation (sham vs. active in anodal stimulation of the left DLPFC with cathodal stimulation of the right DLPFC [F(1,55= 5.29,  P=0.019], but not the inverse polarity worsened accuracy in the 2-back working memory task. There were also no statistically signi.cant changes in speed of working memory [F(1,55= 0.458 ,P=0.502] related to type or order of stimulation..Discussion: The results would imply to a polarity dependence of bilateral tDCS of working memory. Left anodal/ right cathodal stimulation of DLPFC could impair working memory, while the reverser stimulation had no effect. Meaning that bilateral stimulation of DLFC would not be a useful procedure to improve working memory. Further studies are required to understand subtle effects of different tDCS stimulation/inhibition electrode positioning on the working memory.

  6. Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism

    NARCIS (Netherlands)

    van Nimwegen, Lonneke J. M.; Storosum, Jitschak G.; Blumer, Regje M. E.; Allick, Gideon; Venema, Henk W.; de Haan, Lieuwe; Becker, Hiske; van Amelsvoort, Therese; Ackermans, Mariette T.; Fliers, Eric; Serlie, Mireille J. M.; Sauerwein, Hans P.

    2008-01-01

    OBJECTIVE: Our objective was to measure insulin sensitivity and body composition in antipsychotic-naive patients with DSM IV schizophrenia and/or schizoaffective disorder compared with matched controls. DESIGN: Seven antipsychotic medication-naive patients fulfilling the DSM IV A criteria for

  7. On time-dependent diffusion coefficients arising from stochastic processes with memory

    Science.gov (United States)

    Carpio-Bernido, M. Victoria; Barredo, Wilson I.; Bernido, Christopher C.

    2017-08-01

    Time-dependent diffusion coefficients arise from anomalous diffusion encountered in many physical systems such as protein transport in cells. We compare these coefficients with those arising from analysis of stochastic processes with memory that go beyond fractional Brownian motion. Facilitated by the Hida white noise functional integral approach, diffusion propagators or probability density functions (pdf) are obtained and shown to be solutions of modified diffusion equations with time-dependent diffusion coefficients. This should be useful in the study of complex transport processes.

  8. Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation.

    Science.gov (United States)

    Lee, Michael L; Katsuyama, Ângela M; Duge, Leanne S; Sriram, Chaitra; Krushelnytskyy, Mykhaylo; Kim, Jeansok J; de la Iglesia, Horacio O

    2016-11-01

    Sleep is important for consolidation of hippocampus-dependent memories. It is hypothesized that the temporal sequence of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep is critical for the weakening of nonadaptive memories and the subsequent transfer of memories temporarily stored in the hippocampus to more permanent memories in the neocortex. A great body of evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations that induce sleep deprivation or stage-specific sleep deprivation. We exploit an experimental model of circadian desynchrony in which intact animals are not deprived of any sleep stage but show fragmentation of REM and NREM sleep within nonfragmented sleep bouts. We test the hypothesis that the shortening of NREM and REM sleep durations post-training will impair memory consolidation irrespective of total sleep duration. When circadian-desynchronized animals are trained in a hippocampus-dependent contextual fear-conditioning task they show normal short-term memory but impaired long-term memory consolidation. This impairment in memory consolidation is positively associated with the post-training fragmentation of REM and NREM sleep but is not significantly associated with the fragmentation of total sleep or the total amount of delta activity. We also show that the sleep stage fragmentation resulting from circadian desynchrony has no effect on hippocampus-dependent spatial memory and no effect on hippocampus-independent cued fear-conditioning memory. Our findings in an intact animal model, in which sleep deprivation is not a confounding factor, support the hypothesis that the stereotypic sequence and duration of sleep stages play a specific role in long-term hippocampus-dependent fear memory consolidation. © 2016 Associated Professional Sleep Societies, LLC.

  9. Analysis of antigen-specific B-cell memory directly ex vivo.

    Science.gov (United States)

    McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

    2004-01-01

    Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

  10. Memory-dependent derivatives theory of thermo-viscoelasticity involving two-temperature

    Energy Technology Data Exchange (ETDEWEB)

    Ezzat, M. A. [Alexandria University, Alexandria (Egypt); El-Bary, A. A. [Arab Academy for Science and Technology, Alexandria (Egypt)

    2015-10-15

    A new model of two-temperature generalized thermo-viscoelasticity theory based on memory-dependent derivative is constructed. The equations of the new model are applied to one-dimensional problem of a half-space. The bounding surface is taken to be traction free and subjected to a time dependent thermal shock. Laplace transforms technique is used. A direct approach is applied to obtain the exact formulas of heat flux, temperature, stresses, displacement and strain in the Laplace transform domain. Application is employed to our problem to get the solution in the complete form. The considered variables are presented graphically and discussions are made.

  11. Long-term memory for instrumental responses does not undergo protein synthesis-dependent reconsolidation upon retrieval.

    Science.gov (United States)

    Hernandez, Pepe J; Kelley, Ann E

    2004-01-01

    Recent evidence indicates that certain forms of memory, upon recall, may return to a labile state requiring the synthesis of new proteins in order to preserve or reconsolidate the original memory trace. While the initial consolidation of "instrumental memories" has been shown to require de novo protein synthesis in the nucleus accumbens, it is not known whether memories of this type undergo protein synthesis-dependent reconsolidation. Here we show that low doses of the protein synthesis inhibitor anisomycin (ANI; 5 or 20 mg/kg) administered systemically in rats immediately after recall of a lever-pressing task potently impaired performance on the following daily test sessions. We determined that the nature of this impairment was attributable to conditioned taste aversion (CTA) to the sugar reinforcer used in the task rather than to mnemonic or motoric impairments. However, by substituting a novel flavored reinforcer (chocolate pellets) prior to the administration of doses of ANI (150 or 210 mg/kg) previously shown to cause amnesia, a strong CTA to chocolate was induced sparing any aversion to sugar. Importantly, when sugar was reintroduced on the following session, we found that memory for the task was not significantly affected by ANI. Thus, these data suggest that memory for a well-learned instrumental response does not require protein synthesis-dependent reconsolidation as a means of long-term maintenance.

  12. Activation of a remote (1-year old) emotional memory interferes with the retrieval of a newly formed hippocampus-dependent memory in rats.

    Science.gov (United States)

    Zoladz, Phillip R; Woodson, James C; Haynes, Vernon F; Diamond, David M

    2010-01-01

    The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.

  13. Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4+ T cells

    Science.gov (United States)

    Liu, Lanxia; Bai, Yuanyuan; Zhu, Dunwan; Song, Liping; Wang, Hai; Dong, Xia; Zhang, Hailing; Leng, Xigang

    2011-06-01

    Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4+ T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4+ T cells. The indirect impact of CS/DNA nanoparticles on naive CD4+ T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4+ T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4+ T cells to explore their direct impact on naive CD4+ T cell differentiation by measuring the release of IL-4 and IFN-γ from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4+ T cells. It was also demonstrated that, when directly exposed to the naive CD4+ T cells, the nanoparticles induced neither the activation of the naive CD4+ T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-γ) that induce naive CD4+ T cell polarization, nor any changes in the differentiation direction of naive CD4+ T cells in the presence of the corresponding cytokines.

  14. Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4+ T cells

    International Nuclear Information System (INIS)

    Liu Lanxia; Bai Yuanyuan; Zhu Dunwan; Song Liping; Wang Hai; Dong Xia; Zhang Hailing; Leng Xigang

    2011-01-01

    Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4 + T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4 + T cells. The indirect impact of CS/DNA nanoparticles on naive CD4 + T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4 + T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4 + T cells to explore their direct impact on naive CD4 + T cell differentiation by measuring the release of IL-4 and IFN-γ from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4 + T cells. It was also demonstrated that, when directly exposed to the naive CD4 + T cells, the nanoparticles induced neither the activation of the naive CD4 + T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-γ) that induce naive CD4 + T cell polarization, nor any changes in the differentiation direction of naive CD4 + T cells in the presence of the corresponding cytokines.

  15. Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

    Science.gov (United States)

    Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

    2010-07-06

    Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

  16. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  17. Enhancement of striatum-dependent memory by conditioned fear is mediated by beta-adrenergic receptors in the basolateral amygdala

    Directory of Open Access Journals (Sweden)

    Travis D. Goode

    2016-06-01

    Full Text Available Emotional arousal can have a profound impact on various learning and memory processes. For example, unconditioned emotional stimuli (e.g., predator odor or anxiogenic drugs enhance dorsolateral striatum (DLS-dependent habit memory. These effects critically depend on a modulatory role of the basolateral complex of the amygdala (BLA. Recent work indicates that, like unconditioned emotional stimuli, exposure to an aversive conditioned stimulus (CS (i.e., a tone previously paired with shock can also enhance consolidation of DLS-dependent habit memory. The present experiments examined whether noradrenergic activity, particularly within the BLA, is required for a fear CS to enhance habit memory consolidation. First, rats underwent a fear conditioning procedure in which a tone CS was paired with an aversive unconditioned stimulus. Over the course of the next five days, rats received training in a DLS-dependent water plus-maze task, in which rats were reinforced to make a consistent body-turn response to reach a hidden escape platform. Immediately after training on days 1–3, rats received post-training systemic (Experiment 1 or intra-BLA (Experiment 2 administration of the β-adrenoreceptor antagonist, propranolol. Immediately after drug administration, half of the rats were re-exposed to the tone CS in the conditioning context (without shock. Post-training CS exposure enhanced consolidation of habit memory in vehicle-treated rats, and this effect was blocked by peripheral (Experiment 1 or intra-BLA (Experiment 2 propranolol administration. The present findings reveal that noradrenergic activity within the BLA is critical for the enhancement of DLS-dependent habit memory as a result of exposure to conditioned emotional stimuli.

  18. Time course of protein synthesis-dependent phase of olfactory memory in the cricket Gryllus bimaculatus.

    Science.gov (United States)

    Matsumoto, Yukihisa; Noji, Sumihare; Mizunami, Makoto

    2003-04-01

    The cricket Gryllus bimaculatus forms a stable olfactory memory that lasts for practically a lifetime. As a first step to elucidate the cellular mechanisms of olfactory learning and memory retention in crickets, we studied the dependency of memory retention on the de novo brain protein synthesis by injecting the protein synthesis inhibitor cycloheximide (CHX) into the head capsule. Injection of CHX inhibited (3)H-leucine incorporation into brain proteins by > 90% for 3 hr. Crickets were trained to associate peppermint odor with water (reward) and vanilla odor with saline solution (non-reward) and were injected with CHX before or at different times after training. Their odor preferences were tested at 2 hr, 1 day and 4 days after training. Memory retention at 2 hr after training was unaffected by CHX injection. However, the level of retention at 1 day and 4 days after training was lowered when CHX was injected 1 hour before training or at 1 hr or 6 hr after training. To study the time course of the development of CHX-sensitive memory phase, crickets that had been injected with CHX at 1 hr after training were tested at different times from 2 to 12 hr after training. The level of retention was unaffected up to 4 hr after training but significantly lowered at 5 hr after training, and the CHX-sensitive memory phase developed gradually during the next several hours. CHX dissociates two phases of olfactory memory in crickets: earlier protein synthesis-independent phase ( 5 hr) protein synthesis-dependent phase.

  19. Context-dependent utility overrides absolute memory as a determinant of choice.

    Science.gov (United States)

    Pompilio, Lorena; Kacelnik, Alex

    2010-01-05

    A core problem of decision theories is that although decisionmakers' preferences depend on learning, their choices could be driven either by learned representations of the physical properties of each alternative (for instance reward sizes) or of the benefit (utility and fitness) experienced from them. Physical properties are independent of the subject's state and context, but utility depends on both. We show that starlings' choices are better explained by memory for context-dependent utility than by representations of the alternatives' physical properties, even when the decisionmakers' state is controlled and they have accurate knowledge about the options' physical properties. Our results support the potential universality of utility-driven preference control.

  20. Naive Fault Tree : formulation of the approach

    NARCIS (Netherlands)

    Rajabalinejad, M

    2017-01-01

    Naive Fault Tree (NFT) accepts a single value or a range of values for each basic event and returns values for the top event. This accommodates the need of commonly used Fault Trees (FT) for precise data making them prone to data concerns and limiting their area of application. This paper extends

  1. miRNA profiling of naive, effector and memory CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Haoquan Wu

    Full Text Available microRNAs have recently emerged as master regulators of gene expression during development and cell differentiation. Although profound changes in gene expression also occur during antigen-induced T cell differentiation, the role of miRNAs in the process is not known. We compared the miRNA expression profiles between antigen-specific naïve, effector and memory CD8+ T cells using 3 different methods--small RNA cloning, miRNA microarray analysis and real-time PCR. Although many miRNAs were expressed in all the T cell subsets, the frequency of 7 miRNAs (miR-16, miR-21, miR-142-3p, miR-142-5p, miR-150, miR-15b and let-7f alone accounted for approximately 60% of all miRNAs, and their expression was several fold higher than the other expressed miRNAs. Global downregulation of miRNAs (including 6/7 dominantly expressed miRNAs was observed in effector T cells compared to naïve cells and the miRNA expression levels tended to come back up in memory T cells. However, a few miRNAs, notably miR-21 were higher in effector and memory T cells compared to naïve T cells. These results suggest that concomitant with profound changes in gene expression, miRNA profile also changes dynamically during T cell differentiation. Sequence analysis of the cloned mature miRNAs revealed an extensive degree of end polymorphism. While 3'end polymorphisms dominated, heterogeneity at both ends, resembling drosha/dicer processing shift was also seen in miR-142, suggesting a possible novel mechanism to generate new miRNA and/or to diversify miRNA target selection. Overall, our results suggest that dynamic changes in the expression of miRNAs may be important for the regulation of gene expression during antigen-induced T cell differentiation. Our study also suggests possible novel mechanisms for miRNA biogenesis and function.

  2. A kinase-dependent feedforward loop affects CREBB stability and long term memory formation.

    Science.gov (United States)

    Lee, Pei-Tseng; Lin, Guang; Lin, Wen-Wen; Diao, Fengqiu; White, Benjamin H; Bellen, Hugo J

    2018-02-23

    In Drosophila , long-term memory (LTM) requires the cAMP-dependent transcription factor CREBB, expressed in the mushroom bodies (MB) and phosphorylated by PKA. To identify other kinases required for memory formation, we integrated Trojan exons encoding T2A-GAL4 into genes encoding putative kinases and selected for genes expressed in MB. These lines were screened for learning/memory deficits using UAS-RNAi knockdown based on an olfactory aversive conditioning assay. We identified a novel, conserved kinase, Meng-Po ( MP , CG11221 , SBK1 in human), the loss of which severely affects 3 hr memory and 24 hr LTM, but not learning. Remarkably, memory is lost upon removal of the MP protein in adult MB but restored upon its reintroduction. Overexpression of MP in MB significantly increases LTM in wild-type flies showing that MP is a limiting factor for LTM. We show that PKA phosphorylates MP and that both proteins synergize in a feedforward loop to control CREBB levels and LTM. key words: Drosophila, Mushroom bodies, SBK1, deGradFP, T2A-GAL4, MiMIC.

  3. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-01-01

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory. DOI: http://dx.doi.org/10.7554/eLife.17769.001 PMID:27919318

  4. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process.

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-12-06

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

  5. Improving Naive Bayes with Online Feature Selection for Quick Adaptation to Evolving Feature Usefulness

    Energy Technology Data Exchange (ETDEWEB)

    Pon, R K; Cardenas, A F; Buttler, D J

    2007-09-19

    The definition of what makes an article interesting varies from user to user and continually evolves even for a single user. As a result, for news recommendation systems, useless document features can not be determined a priori and all features are usually considered for interestingness classification. Consequently, the presence of currently useless features degrades classification performance [1], particularly over the initial set of news articles being classified. The initial set of document is critical for a user when considering which particular news recommendation system to adopt. To address these problems, we introduce an improved version of the naive Bayes classifier with online feature selection. We use correlation to determine the utility of each feature and take advantage of the conditional independence assumption used by naive Bayes for online feature selection and classification. The augmented naive Bayes classifier performs 28% better than the traditional naive Bayes classifier in recommending news articles from the Yahoo! RSS feeds.

  6. Hemispheric Specialization and Recognition Memory for Abstract and Realistic Pictures: A Comparison of Painters and Laymen

    Science.gov (United States)

    Vogt, S.; Magnussen, S.

    2005-01-01

    Recognition memory and hemispheric specialization were assessed for abstract colour/black and white pictures of sport situations in painters and visually naive subjects using a forced choice yes/no tachistoscopic procedure. Reaction times showed a significant three-way interaction of picture type, expertise, and visual field, indicating that…

  7. Neurocognitive Mechanisms of Prejudice Formation: The Role of Time-Dependent Memory Consolidation.

    Science.gov (United States)

    Enge, Luke R; Lupo, Amber K; Zárate, Michael A

    2015-07-01

    Prejudice is generally thought to derive from learned, emotion-laden experiences. The mechanisms underlying the formation of prejudice over time, however, remain unknown. In the present research, we proposed and tested hypotheses regarding prejudice formation derived from research on memory consolidation and social perception. We hypothesized that time-dependent memory consolidation would produce better implicit memory for negative out-group information and positive in-group information, compared with negative in-group information and positive out-group information. Fifty undergraduates learned positive and negative information about racial in-group (Latino) and out-group (African American) targets. Participants returned after both a short time delay (2-6 hr after the learning session) and a long time delay (48 hr after the learning session) to complete a lexical decision task. Results demonstrated that participants responded to information consistent with an in-group bias faster after a long time delay than after a short time delay. Our findings have important implications for the study of social perception and memory consolidation. © The Author(s) 2015.

  8. The effects of emotion regulation on explicit memory depend on strategy and testing method.

    Science.gov (United States)

    Knight, Marisa; Ponzio, Allison

    2013-12-01

    Although previous work has shown that emotion regulation strategies can influence memory, the mechanisms through which different strategies produce different memory outcomes are not well understood. We examined how two cognitive reappraisal strategies with similar elaboration demands but diverging effects on visual attention and emotional arousal influenced explicit memory for emotional stimuli and for the strategies used to evaluate the stimuli. At encoding, participants used reappraisal to increase and decrease the personal relevance of neutral and emotional pictures. In two experiments, recall accuracy was highest for emotional pictures featured on increase trials, intermediate for emotional pictures featured on look (respond naturally) trials, and lowest for emotional pictures featured on decrease trials. This recall pattern emerged after a short delay (15 min) and persisted over a longer delay (48 hr). Memory accuracy for the strategies used to evaluate the pictures showed a different pattern: Strategy memory was better for emotional pictures featured on decrease and increase trials than for pictures featured on look trials. Our findings show that the effects of emotion regulation on memory depend both on the particular strategy engaged and the particular aspect of memory being tested.

  9. Sleep-dependent memory consolidation in patients with sleep disorders.

    Science.gov (United States)

    Cipolli, Carlo; Mazzetti, Michela; Plazzi, Giuseppe

    2013-04-01

    Sleep can improve the off-line memory consolidation of new items of declarative and non-declarative information in healthy subjects, whereas acute sleep loss, as well as sleep restriction and fragmentation, impair consolidation. This suggests that, by modifying the amount and/or architecture of sleep, chronic sleep disorders may also lead to a lower gain in off-line consolidation, which in turn may be responsible for the varying levels of impaired performance at memory tasks usually observed in sleep-disordered patients. The experimental studies conducted to date have shown specific impairments of sleep-dependent consolidation overall for verbal and visual declarative information in patients with primary insomnia, for verbal declarative information in patients with obstructive sleep apnoeas, and for visual procedural skills in patients with narcolepsy-cataplexy. These findings corroborate the hypothesis that impaired consolidation is a consequence of the chronically altered organization of sleep. Moreover, they raise several novel questions as to: a) the reversibility of consolidation impairment in the case of effective treatment, b) the possible negative influence of altered prior sleep also on the encoding of new information, and c) the relationships between altered sleep and memory impairment in patients with other (medical, psychiatric or neurological) diseases associated with quantitative and/or qualitative changes of sleep architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Neurophysiological capacity in a working memory task differentiates dependent from nondependent heavy drinkers and controls.

    Science.gov (United States)

    Wesley, Michael J; Lile, Joshua A; Fillmore, Mark T; Porrino, Linda J

    2017-06-01

    Determining the neurobehavioral profiles that differentiate heavy drinkers who are and are not alcohol dependent will inform treatment efforts. Working memory is linked to substance use disorders and can serve as a representation of the demand placed on the neurophysiology associated with cognitive control. Behavior and brain activity (via fMRI) were recorded during an N-Back working memory task in controls (CTRL), nondependent heavy drinkers (A-ND) and dependent heavy drinkers (A-D). Typical and novel step-wise analyses examined profiles of working memory load and increasing task demand, respectively. Performance was significantly decreased in A-D during high working memory load (2-Back), compared to CTRL and A-ND. Analysis of brain activity during high load (0-Back vs. 2- Back) showed greater responses in the dorsal lateral and medial prefrontal cortices of A-D than CTRL, suggesting increased but failed compensation. The step-wise analysis revealed that the transition to Low Demand (0-Back to 1-Back) was associated with robust increases and decreases in cognitive control and default-mode brain regions, respectively, in A-D and A-ND but not CTRL. The transition to High Demand (1-Back to 2-Back) resulted in additional engagement of these networks in A-ND and CTRL, but not A-D. Heavy drinkers engaged working memory neural networks at lower demand than controls. As demand increased, nondependent heavy drinkers maintained control performance but relied on additional neurophysiological resources, and dependent heavy drinkers did not display further resource engagement and had poorer performance. These results support targeting these brain areas for treatment interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The Hayflick Limit May Determine the Effective Clonal Diversity of Naive T Cells.

    Science.gov (United States)

    Ndifon, Wilfred; Dushoff, Jonathan

    2016-06-15

    Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.) The causes of this observation are incompletely understood. A previous study proposed that it might result from the emergence of certain rare, replication-enhancing mutations in T cells. In this paper, we propose an even simpler explanation: that it results from the loss of T cells that have attained replicative senescence (i.e., the Hayflick limit). Stochastic numerical simulations of naive T cell population dynamics, based on experimental parameters, show that the rate of homeostatic T cell proliferation increases after the age of ∼60 y because naive T cells collectively approach replicative senescence. This leads to a sharp decline of effective clonal diversity after ∼70 y, in agreement with empirical data. A mathematical analysis predicts that, without an increase in the naive T cell proliferation rate, this decline will occur >50 yr later than empirically observed. These results are consistent with a model in which exhaustion of the proliferative capacity of naive T cells causes a sharp decline of their effective clonal diversity and imply that therapeutic potentiation of thymopoiesis might either prevent or reverse this outcome. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

    Science.gov (United States)

    Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

    2013-07-01

    Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

  13. Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4{sup +} T cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu Lanxia; Bai Yuanyuan; Zhu Dunwan; Song Liping; Wang Hai; Dong Xia; Zhang Hailing; Leng Xigang, E-mail: lengxg@bme.org.cn [Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Lab of Bioengineering, Institute of Biomedical Engineering (China)

    2011-06-15

    Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4{sup +} T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4{sup +} T cells. The indirect impact of CS/DNA nanoparticles on naive CD4{sup +} T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4{sup +} T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4{sup +} T cells to explore their direct impact on naive CD4{sup +} T cell differentiation by measuring the release of IL-4 and IFN-{gamma} from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4{sup +} T cells. It was also demonstrated that, when directly exposed to the naive CD4{sup +} T cells, the nanoparticles induced neither the activation of the naive CD4{sup +} T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-{gamma}) that induce naive CD4{sup +} T cell polarization, nor any changes in the differentiation direction of naive CD4{sup +} T cells in the presence of the corresponding

  14. Three naive Bayes approaches for discrimination-free classification

    NARCIS (Netherlands)

    Calders, T.G.K.; Verwer, S.E.

    2010-01-01

    In this paper, we investigate how to modify the naive Bayes classifier in order to perform classification that is restricted to be independent with respect to a given sensitive attribute. Such independency restrictions occur naturally when the decision process leading to the labels in the data-set

  15. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner

    NARCIS (Netherlands)

    Gupta, V.K.; Scheunemann, L.; Eisenberg, T.; Mertel, S.; Bhukel, A.; Koemans, T.S.; Kramer, J.M.; Liu, K.S.; Schroeder, S.; Stunnenberg, H.G.; Sinner, F.; Magnes, C.; Pieber, T.R.; Dipt, S.; Fiala, A.; Schenck, A.; Schwaerzel, M.; Madeo, F.; Sigrist, S.J.

    2013-01-01

    Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the

  16. PERBANDINGAN K-NEAREST NEIGHBOR DAN NAIVE BAYES UNTUK KLASIFIKASI TANAH LAYAK TANAM POHON JATI

    Directory of Open Access Journals (Sweden)

    Didik Srianto

    2016-10-01

    Full Text Available Data mining adalah proses menganalisa data dari perspektif yang berbeda dan menyimpulkannya menjadi informasi-informasi penting yang dapat dipakai untuk meningkatkan keuntungan, memperkecil biaya pengeluaran, atau bahkan keduanya. Secara teknis, data mining dapat disebut sebagai proses untuk menemukan korelasi atau pola dari ratusan atau ribuan field dari sebuah relasional database yang besar. Pada perum perhutani KPH SEMARANG saat ini masih menggunakan cara manual untuk menentukan jenis tanaman (jati / non jati. K-Nearest Neighbour atau k-NN merupakan algoritma data mining yang dapat digunakan untuk proses klasifikasi dan regresi. Naive bayes Classifier merupakan suatu teknik yang dapat digunakan untuk teknik klasifikasi. Pada penelitian ini k-NN dan Naive Bayes akan digunakan untuk mengklasifikasi data pohon jati dari perum perhutani KPH SEMARANG. Yang mana hasil klasifikasi dari k-NN dan Naive Bayes akan dibandingkan hasilnya. Pengujian dilakukan menggunakan software RapidMiner. Setelah dilakukan pengujian k-NN dianggap lebih baik dari Naife Bayes dengan akurasi 96.66% dan 82.63. Kata kunci -k-NN,Klasifikasi,Naive Bayes,Penanaman Pohon Jati

  17. Ensemble coding of context-dependent fear memory in the amygdala.

    Science.gov (United States)

    Orsini, Caitlin A; Yan, Chen; Maren, Stephen

    2013-01-01

    After fear conditioning, presenting the conditioned stimulus (CS) alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex (PFC) and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH). This method exploits the intracellular expression profile of the immediate early gene (IEG), Arc, to visualize neuronal activation patterns to two different behavioral experiences. Rats were fear conditioned in one context and extinguished in another; 24 h later, they were sequentially exposed to the CS in the extinction context and another context. Control rats were also tested in each context, but were never extinguished. We assessed Arc mRNA expression within the basal amygdala (BA), lateral amygdala (LA), ventral hippocampus (VH), prelimbic cortex (PL) and infralimbic cortex (IL). We observed that the sequential retention tests induced context-dependent patterns of Arc expression in the BA, LA, and IL of extinguished rats; this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled) neurons than extinguished animals. Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories after extinction.

  18. Ensemble coding of context-dependent fear memory in the amygdala

    Directory of Open Access Journals (Sweden)

    Caitlin A Orsini

    2013-12-01

    Full Text Available After fear conditioning, presenting the conditioned stimulus (CS alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH. This method exploits the intracellular expression profile of the immediate early gene, Arc, to visualize neuronal activation patterns to two different behavioral experiences. Rats were fear conditioned in one context and extinguished in another; twenty-four hours later, they were sequentially exposed to the CS in the extinction context and another context. Control rats were also tested in each context, but were never extinguished. We assessed Arc mRNA expression within the basal amygdala (BA, lateral amygdala (LA, ventral hippocampus (VH, prelimbic cortex (PL and infralimbic cortex (IL. We observed that the sequential retention tests induced context-dependent patterns of Arc expression in the BA, LA, and IL of extinguished rats; this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled neurons than extinguished animals. Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories after extinction.

  19. Incorporating pion effects into the naive quark model

    International Nuclear Information System (INIS)

    Nogami, Y.; Ohtuska, N.

    1982-01-01

    A hybrid of the naive nonrelativistic quark model and the Chew-Low model is proposed. The pion is treated as an elementary particle which interacts with the ''bare baryon'' or ''baryon core'' via the Chew-Low interaction. The baryon core, which is the source of the pion interaction, is described by the naive nonrelativistic quark model. It turns out that the baryon-core radius has to be as large as 0.8 fm, and consequently the cutoff momentum Λ for the pion interaction is < or approx. =3m/sub π/, m/sub π/ being the pion mass. Because of this small Λ (as compared with Λapprox. nucleon mass in the old Chew-Low model) the effects of the pion cloud are strongly suppressed. The baryon masses, baryon magnetic moments, and the nucleon charge radii can be reproduced quite well. However, we found it singularly difficult to fit the axial-vector weak decay constant g/sub A/

  20. Oxide Structure Dependence of SiO2/SiOx/3C-SiC/n-Type Si Nonvolatile Resistive Memory on Memory Operation Characteristics

    Science.gov (United States)

    Yamaguchi, Yuichiro; Shouji, Masatsugu; Suda, Yoshiyuki

    2012-11-01

    We have investigated the dependence of the oxide layer structure of our previously proposed metal/SiO2/SiOx/3C-SiC/n-Si/metal metal-insulator-semiconductor (MIS) resistive memory device on the memory operation characteristics. The current-voltage (I-V) measurement and X-ray photoemission spectroscopy results suggest that SiOx defect states mainly caused by the oxidation of 3C-SiC at temperatures below 1000 °C are related to the hysteresis memory behavior in the I-V curve. By restricting the SiOx interface region, the number of switching cycles and the on/off current ratio are more enhanced. Compared with a memory device formed by one-step or two-step oxidation of 3C-SiC, a memory device formed by one-step oxidation of Si/3C-SiC exhibits a more restrictive SiOx interface with a more definitive SiO2 layer and higher memory performances for both the endurance switching cycle and on/off current ratio.

  1. Hydrodynamic perspective on memory in time-dependent density-functional theory

    International Nuclear Information System (INIS)

    Thiele, M.; Kuemmel, S.

    2009-01-01

    The adiabatic approximation of time-dependent density-functional theory is studied in the context of nonlinear excitations of two-electron singlet systems. We compare the exact time evolution of these systems to the adiabatically exact one obtained from time-dependent Kohn-Sham calculations relying on the exact ground-state exchange-correlation potential. Thus, we can show under which conditions the adiabatic approximation breaks down and memory effects become important. The hydrodynamic formulation of quantum mechanics allows us to interpret these results and relate them to dissipative effects in the Kohn-Sham system. We show how the breakdown of the adiabatic approximation can be inferred from the rate of change of the ground-state noninteracting kinetic energy.

  2. Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

    Science.gov (United States)

    Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

    2016-01-01

    Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Context-dependent memory traces in the crab's mushroom bodies: Functional support for a common origin of high-order memory centers.

    Science.gov (United States)

    Maza, Francisco Javier; Sztarker, Julieta; Shkedy, Avishag; Peszano, Valeria Natacha; Locatelli, Fernando Federico; Delorenzi, Alejandro

    2016-12-06

    The hypothesis of a common origin for the high-order memory centers in bilateral animals is based on the evidence that several key features, including gene expression and neuronal network patterns, are shared across several phyla. Central to this hypothesis is the assumption that the arthropods' higher order neuropils of the forebrain [the mushroom bodies (MBs) of insects and the hemiellipsoid bodies (HBs) of crustaceans] are homologous structures. However, even though involvement in memory processes has been repeatedly demonstrated for the MBs, direct proof of such a role in HBs is lacking. Here, through neuroanatomical and immunohistochemical analysis, we identified, in the crab Neohelice granulata, HBs that resemble the calyxless MBs found in several insects. Using in vivo calcium imaging, we revealed training-dependent changes in neuronal responses of vertical and medial lobes of the HBs. These changes were stimulus-specific, and, like in the hippocampus and MBs, the changes reflected the context attribute of the memory trace, which has been envisioned as an essential feature for the HBs. The present study constitutes functional evidence in favor of a role for the HBs in memory processes, and provides key physiological evidence supporting a common origin of the arthropods' high-order memory centers.

  4. Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

    Directory of Open Access Journals (Sweden)

    Wallace Diana

    2008-10-01

    Full Text Available Abstract Background Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years. Methods Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV seropositivity was assessed by ELISA in adolescents. Results HIV-negative Malawian adolescents were shown to have a lower percentage of naïve T cells (CD45RO-CD62Lhi CD11alo, a higher proportion of memory T cells and a higher percentage of CD28- memory (CD28-CD45RO+ T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+ T cells and a higher percentage of stable memory (CD45RA+CCR7- T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59, compared to 21/58 (36% of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naïve T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naïve and memory T cell populations were observed in cord blood samples from the two sites. Conclusion It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.

  5. Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment.

    Science.gov (United States)

    Pace-Schott, Edward F; Spencer, Rebecca M C

    2015-01-01

    Sleep quality and architecture as well as sleep's homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep's (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as well as a phase advance (moved earlier in time) of the brain's circadian clock. With mild cognitive impairment (MCI) there are further reductions of sleep quality, SWS, spindles, and percent REM, all of which further diminish, along with a profound disruption of circadian rhythmicity, with the conversion to Alzheimer's disease (AD). Sleep disorders may represent risk factors for dementias (e.g., REM Behavior Disorder presages Parkinson's disease) and sleep disorders are themselves extremely prevalent in neurodegenerative diseases. Working memory , formation of new episodic memories, and processing speed all decline with healthy aging whereas semantic, recognition, and emotional declarative memory are spared. In MCI, episodic and working memory further decline along with declines in semantic memory. In young adults, sleep-dependent memory consolidation (SDC) is widely observed for both declarative and procedural memory tasks. However, with healthy aging, although SDC for declarative memory is preserved, certain procedural tasks, such as motor-sequence learning, do not show SDC. In younger adults, fragmentation of sleep can reduce SDC, and a normative increase in sleep fragmentation may account for reduced SDC with healthy aging. Whereas sleep disorders such as insomnia, obstructive sleep apnea, and narcolepsy can impair SDC in the absence of neurodegenerative changes, the incidence of sleep disorders increases both with normal aging and, further, with neurodegenerative disease. Specific features of sleep architecture, such as sleep spindles and SWS are strongly linked to SDC. Diminution of these features with healthy aging

  6. Individual Differences in Working Memory Capacity Predict Sleep-Dependent Memory Consolidation

    Science.gov (United States)

    Fenn, Kimberly M.; Hambrick, David Z.

    2012-01-01

    Decades of research have established that "online" cognitive processes, which operate during conscious encoding and retrieval of information, contribute substantially to individual differences in memory. Furthermore, it is widely accepted that "offline" processes during sleep also contribute to memory performance. However, the question of whether…

  7. Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

    Science.gov (United States)

    Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

    2014-06-01

    In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

  8. Modulating epigenetic memory through vitamins and TET: implications for regenerative medicine and cancer treatment.

    Science.gov (United States)

    Hore, Timothy A

    2017-06-01

    Vitamins A and C represent unrelated sets of small molecules that are essential to the human diet and have recently been shown to intensify erasure of epigenetic memory in naive embryonic stem cells. These effects are driven by complementary enhancement of the ten-eleven translocation (TET) demethylases - vitamin A stimulates TET expression, whereas vitamin C potentiates TET catalytic activity. Vitamin A and C cosupplementation synergistically enhances reprogramming of differentiated cells to the naive state, but overuse may exaggerate instability of imprinted genes. As such, optimizing their use in culture media will be important for regenerative medicine and mammalian transgenics. In addition, mechanistic perception of how these vitamins interact with the epigenome may be relevant for understanding cancer and improving patient treatment.

  9. Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets.

    Directory of Open Access Journals (Sweden)

    Makoto Mizunami

    Full Text Available Ca(2+/calmodulin (CaM-dependent protein kinase II (CaMKII is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+/CaM and cAMP signaling participates in long-term memory (LTM formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM. Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+ influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+ signaling and cAMP signaling for LTM formation, a new role of Ca

  10. Orientation dependence of shape memory and super elastic effects in Ti-30% Ni-20% Cu single crystals

    International Nuclear Information System (INIS)

    Chumlyakov, Yu.I.; Kireeva, I.V.

    1999-01-01

    Single crystals of Ti-30% Ni-20% Cu (at.%) alloy experiencing B2-B19 martensitic transformation are used to study the dependence of deforming stress σ cr , shape memory effect and super elasticity on test temperature, crystal orientation and the sign of tension/compression stresses. It is shown that experimental values of shape memory effect and super elasticity as well as their dependences on orientation and loading regime are described within the frameworks of the model taking into account lattice distortions only. The orientation dependence and axial stress asymmetry in the temperature range of stress-induced martensite formation are determined by the dependence of lattice distortion during B2-B19 martensitic transformations on the orientation and the sign of applied stresses [ru

  11. Naive Bayesian classifiers for multinomial features: a theoretical analysis

    CSIR Research Space (South Africa)

    Van Dyk, E

    2007-11-01

    Full Text Available The authors investigate the use of naive Bayesian classifiers for multinomial feature spaces and derive error estimates for these classifiers. The error analysis is done by developing a mathematical model to estimate the probability density...

  12. Partial reconstitution of virus-specific memory CD8+ T cells following whole body γ-irradiation

    International Nuclear Information System (INIS)

    Grayson, Jason M.; Laniewski, Nathan G.; Holbrook, Beth C.

    2006-01-01

    CD8 + memory T cells are critical in providing immunity to viral infection. Previous studies documented that antigen-specific CD8 + memory T cells are more resistant to radiation-induced apoptosis than naive T cells. Here, we determined the number and in vivo function of memory CD8 + T cells as immune reconstitution progressed following irradiation. Immediately following irradiation, the number of memory CD8 + T cells declined 80%. As reconstitution progressed, the number of memory cells reached a zenith at 33% of pre-irradiation levels, and was maintained for 120 days post-irradiation. In vitro, memory CD8 + T cells were able to produce cytokines at all times post-irradiation, but when adoptively transferred, they were not able to expand upon rechallenge immediately following irradiation, but regained this ability as reconstitution progressed. When proliferation was examined in vitro, irradiated memory CD8 + T cells were able to respond to mitogenic growth but were unable to divide

  13. Neural markers of negative symptom outcomes in distributed working memory brain activity of antipsychotic-naive schizophrenia patients

    DEFF Research Database (Denmark)

    Nejad, Ayna B.; Madsen, Kristoffer H.; Ebdrup, Bjørn H.

    2013-01-01

    Since working memory deficits in schizophrenia have been linked to negative symptoms, we tested whether features of the one could predict the treatment outcome in the other. Specifically, we hypothesized that working memory-related functional connectivity at pre-treatment can predict improvement...

  14. Evidence for a Peripheral Olfactory Memory in Imprinted Salmon

    Science.gov (United States)

    Nevitt, Gabrielle A.; Dittman, Andrew H.; Quinn, Thomas P.; Moody, William J., Jr.

    1994-05-01

    The remarkable homing ability of salmon relies on olfactory cues, but its cellular basis is unknown. To test the role of peripheral olfactory receptors in odorant memory retention, we imprinted coho salmon (Oncorhynchus kisutch) to micromolar concentrations of phenyl ethyl alcohol during parr-smolt transformation. The following year, we measured phenyl ethyl alcohol responses in the peripheral receptor cells using patch clamp. Cells from imprinted fish showed increased sensitivity to phenyl ethyl alcohol compared either to cells from naive fish or to sensitivity to another behaviorally important odorant (L-serine). Field experiments verified an increased behavioral preference for phenyl ethyl alcohol by imprinted salmon as adults. Thus, some component of the imprinted olfactory homestream memory appears to be retained peripherally.

  15. Surface effects of electrode-dependent switching behavior of resistive random-access memory

    KAUST Repository

    Ke, Jr Jian

    2016-09-26

    The surface effects of ZnO-based resistive random-access memory (ReRAM) were investigated using various electrodes. Pt electrodes were found to have better performance in terms of the device\\'s switching functionality. A thermodynamic model of the oxygen chemisorption process was proposed to explain this electrode-dependent switching behavior. The temperature-dependent switching voltage demonstrates that the ReRAM devices fabricated with Pt electrodes have a lower activation energy for the chemisorption process, resulting in a better resistive switching performance. These findings provide an in-depth understanding of electrode-dependent switching behaviors and can serve as design guidelines for future ReRAM devices.

  16. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

    Science.gov (United States)

    Heisler, Jillian M; O'Connor, Jason C

    2015-11-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

  17. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

    Science.gov (United States)

    Heisler, Jillian M.; O’Connor, Jason C.

    2015-01-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

  18. Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

    Science.gov (United States)

    Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

    2016-09-01

    Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

  19. Scaling dependence of memory windows and different carrier charging behaviors in Si nanocrystal nonvolatile memory devices

    Science.gov (United States)

    Yu, Jie; Chen, Kun-ji; Ma, Zhong-yuan; Zhang, Xin-xin; Jiang, Xiao-fan; Wu, Yang-qing; Huang, Xin-fan; Oda, Shunri

    2016-09-01

    Based on the charge storage mode, it is important to investigate the scaling dependence of memory performance in silicon nanocrystal (Si-NC) nonvolatile memory (NVM) devices for its scaling down limit. In this work, we made eight kinds of test key cells with different gate widths and lengths by 0.13-μm node complementary metal oxide semiconductor (CMOS) technology. It is found that the memory windows of eight kinds of test key cells are almost the same of about 1.64 V @ ± 7 V/1 ms, which are independent of the gate area, but mainly determined by the average size (12 nm) and areal density (1.8 × 1011/cm2) of Si-NCs. The program/erase (P/E) speed characteristics are almost independent of gate widths and lengths. However, the erase speed is faster than the program speed of test key cells, which is due to the different charging behaviors between electrons and holes during the operation processes. Furthermore, the data retention characteristic is also independent of the gate area. Our findings are useful for further scaling down of Si-NC NVM devices to improve the performance and on-chip integration. Project supported by the State Key Development Program for Basic Research of China (Grant No. 2010CB934402) and the National Natural Science Foundation of China (Grant Nos. 11374153, 61571221, and 61071008).

  20. Acoustic Masking Disrupts Time-Dependent Mechanisms of Memory Encoding in Word-List Recall

    Science.gov (United States)

    Cousins, Katheryn A.Q.; Dar, Jonathan; Wingfield, Arthur; Miller, Paul

    2013-01-01

    Recall of recently heard words is affected by the clarity of presentation: even if all words are presented with sufficient clarity for successful recognition, those that are more difficult to hear are less likely to be recalled. Such a result demonstrates that memory processing depends on more than whether a word is simply “recognized” versus “not-recognized”. More surprising is that when a single item in a list of spoken words is acoustically masked, prior words that were heard with full clarity are also less likely to be recalled. To account for such a phenomenon, we developed the Linking by Active Maintenance Model (LAMM). This computational model of perception and encoding predicts that these effects are time dependent. Here we challenge our model by investigating whether and how the impact of acoustic masking on memory depends on presentation rate. We find that a slower presentation rate causes a more disruptive impact of stimulus degradation on prior, clearly heard words than does a fast rate. These results are unexpected according to prior theories of effortful listening, but we demonstrate that they can be accounted for by LAMM. PMID:24838269

  1. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway.

    Science.gov (United States)

    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G; Mungenast, Alison E; Deisseroth, Karl; Tsai, Li-Huei

    2015-06-09

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.

  2. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

    Science.gov (United States)

    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G.; Mungenast, Alison E.; Deisseroth, Karl; Tsai, Li-Huei

    2015-01-01

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation. PMID:25995364

  3. Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

    Science.gov (United States)

    Jafari, M R; Zarrindast, M R; Djahanguiri, B

    2004-10-01

    Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

  4. Context-dependent memory traces in the crab’s mushroom bodies: Functional support for a common origin of high-order memory centers

    Science.gov (United States)

    Maza, Francisco Javier; Sztarker, Julieta; Shkedy, Avishag; Peszano, Valeria Natacha; Locatelli, Fernando Federico; Delorenzi, Alejandro

    2016-01-01

    The hypothesis of a common origin for the high-order memory centers in bilateral animals is based on the evidence that several key features, including gene expression and neuronal network patterns, are shared across several phyla. Central to this hypothesis is the assumption that the arthropods’ higher order neuropils of the forebrain [the mushroom bodies (MBs) of insects and the hemiellipsoid bodies (HBs) of crustaceans] are homologous structures. However, even though involvement in memory processes has been repeatedly demonstrated for the MBs, direct proof of such a role in HBs is lacking. Here, through neuroanatomical and immunohistochemical analysis, we identified, in the crab Neohelice granulata, HBs that resemble the calyxless MBs found in several insects. Using in vivo calcium imaging, we revealed training-dependent changes in neuronal responses of vertical and medial lobes of the HBs. These changes were stimulus-specific, and, like in the hippocampus and MBs, the changes reflected the context attribute of the memory trace, which has been envisioned as an essential feature for the HBs. The present study constitutes functional evidence in favor of a role for the HBs in memory processes, and provides key physiological evidence supporting a common origin of the arthropods’ high-order memory centers. PMID:27856766

  5. Generalized Fractional Processes with Long Memory and Time Dependent Volatility Revisited

    Directory of Open Access Journals (Sweden)

    M. Shelton Peiris

    2016-09-01

    Full Text Available In recent years, fractionally-differenced processes have received a great deal of attention due to their flexibility in financial applications with long-memory. This paper revisits the class of generalized fractionally-differenced processes generated by Gegenbauer polynomials and the ARMA structure (GARMA with both the long-memory and time-dependent innovation variance. We establish the existence and uniqueness of second-order solutions. We also extend this family with innovations to follow GARCH and stochastic volatility (SV. Under certain regularity conditions, we give asymptotic results for the approximate maximum likelihood estimator for the GARMA-GARCH model. We discuss a Monte Carlo likelihood method for the GARMA-SV model and investigate finite sample properties via Monte Carlo experiments. Finally, we illustrate the usefulness of this approach using monthly inflation rates for France, Japan and the United States.

  6. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  7. A real-time multichannel memory controller and optimal mapping of memory clients to memory channels

    NARCIS (Netherlands)

    Gomony, M.D.; Akesson, K.B.; Goossens, K.G.W.

    2015-01-01

    Ever-increasing demands for main memory bandwidth and memory speed/power tradeoff led to the introduction of memories with multiple memory channels, such as Wide IO DRAM. Efficient utilization of a multichannel memory as a shared resource in multiprocessor real-time systems depends on mapping of the

  8. Children's Conceptions of Mental Illness: A Naive Theory Approach

    Science.gov (United States)

    Fox, Claudine; Buchanan-Barrow, Eithne; Barrett, Martyn

    2010-01-01

    This paper reports two studies that investigated children's conceptions of mental illness using a naive theory approach, drawing upon a conceptual framework for analysing illness representations which distinguishes between the identity, causes, consequences, curability, and timeline of an illness. The studies utilized semi-structured interviewing…

  9. Short-term memory for event duration: modality specificity and goal dependency.

    Science.gov (United States)

    Takahashi, Kohske; Watanabe, Katsumi

    2012-11-01

    Time perception is involved in various cognitive functions. This study investigated the characteristics of short-term memory for event duration by examining how the length of the retention period affects inter- and intramodal duration judgment. On each trial, a sample stimulus was followed by a comparison stimulus, after a variable delay period (0.5-5 s). The sample and comparison stimuli were presented in the visual or auditory modality. The participants determined whether the comparison stimulus was longer or shorter than the sample stimulus. The distortion pattern of subjective duration during the delay period depended on the sensory modality of the comparison stimulus but was not affected by that of the sample stimulus. When the comparison stimulus was visually presented, the retained duration of the sample stimulus was shortened as the delay period increased. Contrarily, when the comparison stimulus was presented in the auditory modality, the delay period had little to no effect on the retained duration. Furthermore, whenever the participants did not know the sensory modality of the comparison stimulus beforehand, the effect of the delay period disappeared. These results suggest that the memory process for event duration is specific to sensory modality and that its performance is determined depending on the sensory modality in which the retained duration will be used subsequently.

  10. Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C; Branum, K C

    2000-01-01

    The recall of CD8(+) T-cell memory established by infecting H-2(b) mice with an H1N1 influenza A virus provided a measure of protection against an extremely virulent H7N7 virus. The numbers of CD8(+) effector and memory T cells specific for the shared, immunodominant D(b)NP(366) epitope were...... greatly increased subsequent to the H7N7 challenge, and though lung titers remained as high as those in naive controls for 5 days or more, the virus was cleared more rapidly. Expanding the CD8(+) memory T-cell pool (10%) by sequential priming with two different influenza A viruses (H3N2-->H1N1......) gave much better protection. Though the H7N7 virus initially grew to equivalent titers in the lungs of naive and double-primed mice, the replicative phase was substantially controlled within 3 days. This tertiary H7N7 challenge caused little increase in the magnitude of the CD8(+) D(b)NP(366)(+) T...

  11. Surface feature congruency effects in the object-reviewing paradigm are dependent on task memory demands.

    Science.gov (United States)

    Kimchi, Ruth; Pirkner, Yossef

    2014-08-01

    Perception of object continuity depends on establishing correspondence between objects viewed across disruptions in visual information. The role of spatiotemporal information in guiding object continuity is well documented; the role of surface features, however, is controversial. Some researchers have shown an object-specific preview benefit (OSPB)-a standard index of object continuity-only when correspondence could be based on an object's spatiotemporal information, whereas others have found color-based OSPB, suggesting that surface features can also guide object continuity. This study shows that surface feature-based OSPB is dependent on the task memory demands. When the task involved letters and matching just one target letter to the preview ones, no color congruency effect was found under spatiotemporal discontinuity and spatiotemporal ambiguity (Experiments 1-3), indicating that the absence of feature-based OSPB cannot be accounted for by salient spatiotemporal discontinuity. When the task involved complex shapes and matching two target shapes to the preview ones, color-based OSPB was obtained. Critically, however, when a visual working memory task was performed concurrently with the matching task, the presence of a nonspatial (but not a spatial) working memory load eliminated the color-based OSPB (Experiments 4 and 5). These results suggest that the surface feature congruency effects that are observed in the object-reviewing paradigm (with the matching task) reflect memory-based strategies that participants use to solve a memory-demanding task; therefore, they are not reliable measures of online object continuity and cannot be taken as evidence for the role of surface features in establishing object correspondence.

  12. Recent memory for socially transmitted food preferences in rats does not depend on the hippocampus.

    Science.gov (United States)

    Thapa, Rajat; Sparks, Fraser T; Hanif, Wahab; Gulbrandsen, Tine; Sutherland, Robert J

    2014-10-01

    The standard model of systems consolidation holds that the hippocampus (HPC) is involved only in the initial storage and retrieval of a memory. With time hippocampal-neocortical interactions slowly strengthen the neocortical memory, ultimately enabling retrieval of the memory without the HPC. Key support for this idea comes from experiments measuring memory recall in the socially-transmitted food preference (STFP) task in rats. HPC damage within a day or two of STFP learning can abolish recall, but similar damage five or more days after learning has no effect. We hypothesize that disruption of cellular consolidation outside the HPC could contribute to the amnesia with recent memories, perhaps playing a more important role than the loss of HPC. This view predicts that intraHPC infusion of Tetrodotoxin (TTX), which can block conduction of action potentials from the lesion sites, will block the retrograde amnesia in the STFP task. Here we confirm the previously reported retrograde amnesia with neurotoxic HPC damage within the first day after learning, but show that co-administration of TTX with the neurotoxin blocks the retrograde amnesia despite very extensive HPC damage. These results indicate that HPC damage disrupts cellular consolidation of the recent memory elsewhere; STFP memory may not ever depend on the HPC. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Olfactory insights into sleep-dependent learning and memory.

    Science.gov (United States)

    Shanahan, Laura K; Gottfried, Jay A

    2014-01-01

    Sleep is pervasive throughout most of the animal kingdom-even jellyfish and honeybees do it. Although the precise function of sleep remains elusive, research increasingly suggests that sleep plays a key role in memory consolidation. Newly formed memories are highly labile and susceptible to interference, and the sleep period offers an optimal window in which memories can be strengthened or modified. Interestingly, a small but growing research area has begun to explore the ability of odors to modulate memories during sleep. The unique anatomical organization of the olfactory system, including its intimate overlap with limbic systems mediating emotion and memory, and the lack of a requisite thalamic intermediary between the nasal periphery and olfactory cortex, suggests that odors may have privileged access to the brain during sleep. Indeed, it has become clear that the long-held assumption that odors have no impact on the sleeping brain is no longer tenable. Here, we summarize recent studies in both animal and human models showing that odor stimuli experienced in the waking state modulate olfactory cortical responses in sleep-like states, that delivery of odor contextual cues during sleep can enhance declarative memory and extinguish fear memory, and that olfactory associative learning can even be achieved entirely within sleep. Data reviewed here spotlight the emergence of a new research area that should hold far-reaching implications for future neuroscientific investigations of sleep, learning and memory, and olfactory system function. © 2014 Elsevier B.V. All rights reserved.

  14. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells.

    Science.gov (United States)

    Mendoza, Alejandra; Fang, Victoria; Chen, Cynthia; Serasinghe, Madhavika; Verma, Akanksha; Muller, James; Chaluvadi, V Sai; Dustin, Michael L; Hla, Timothy; Elemento, Olivier; Chipuk, Jerry E; Schwab, Susan R

    2017-06-01

    Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P 1 receptor (S1P 1 R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P 1 R on T cells, and that the requirement for S1P 1 R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.

  15. Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

    Science.gov (United States)

    Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

    2013-04-01

    Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

  16. Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.

    Science.gov (United States)

    Leão, Anderson H F F; Medeiros, André M; Apolinário, Gênedy K S; Cabral, Alícia; Ribeiro, Alessandra M; Barbosa, Flávio F; Silva, Regina H

    2016-05-01

    The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 μg, 0.1 μg, and 0.2 μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to

  17. Going the distance: Memory and control processes in active dependency construction.

    Science.gov (United States)

    Wagers, Matthew W; Phillips, Colin

    2014-01-01

    Filler-gap dependencies make strong demands on working memory in language comprehension because they cannot always be immediately resolved. In a series of three reading-time studies, we test the idea that these demands can be decomposed into active maintenance processes and retrieval events. Results indicate that the fact that a displaced phrase exists and the identity of its basic syntactic category both immediately impact comprehension at potential gap sites. In contrast, specific lexical details of the displaced phrase show an immediate effect only for short dependencies and a much later effect for longer dependencies. We argue that coarse-grained information about the filler is actively maintained and is used to make phrase structure parsing decisions, whereas finer grained information is more quickly released from active maintenance and consequently has to be retrieved at the gap site.

  18. Music-dependent memory in immediate and delayed word recall.

    Science.gov (United States)

    Balch, W R; Bowman, K; Mohler, L

    1992-01-01

    Undergraduate volunteers rated a series of words for pleasantness while hearing a particular background music. The subjects in Experiment 1 received, immediately or after a 48-h delay, an unexpected word-recall test in one of the following musical cue contexts: same cue (S), different cue (D), or no cue (N). For immediate recall, context dependency (S-D) was significant but same-cue facilitation (S-N) was not. No cue effects at all were found for delayed recall, and there was a significant interaction between cue and retention interval. A similar interaction was also found in Experiment 3, which was designed to rule out an alternative explanation with respect to distraction. When the different musical selection was changed specifically in either tempo or form (genre), only pieces having an altered tempo produced significantly lower immediate recall compared with the same pieces (Experiment 2). The results support a stimulus generalization view of music-dependent memory.

  19. Sex-dependent dissociation between emotional appraisal and memory: a large-scale behavioral and fMRI study.

    Science.gov (United States)

    Spalek, Klara; Fastenrath, Matthias; Ackermann, Sandra; Auschra, Bianca; Coynel, David; Frey, Julia; Gschwind, Leo; Hartmann, Francina; van der Maarel, Nadine; Papassotiropoulos, Andreas; de Quervain, Dominique; Milnik, Annette

    2015-01-21

    Extensive evidence indicates that women outperform men in episodic memory tasks. Furthermore, women are known to evaluate emotional stimuli as more arousing than men. Because emotional arousal typically increases episodic memory formation, the females' memory advantage might be more pronounced for emotionally arousing information than for neutral information. Here, we report behavioral data from 3398 subjects, who performed picture rating and memory tasks, and corresponding fMRI data from up to 696 subjects. We were interested in the interaction between sex and valence category on emotional appraisal, memory performances, and fMRI activity. The behavioral results showed that females evaluate in particular negative (p pictures, as emotionally more arousing (pinteraction recall females outperformed males not only in positive (p picture recall (p pictures (pinteraction memory advantage during free recall was absent in a recognition setting. We identified activation differences in fMRI, which corresponded to the females' stronger appraisal of especially negative pictures, but no activation differences that reflected the interaction effect in the free recall memory task. In conclusion, females' valence-category-specific memory advantage is only observed in a free recall, but not a recognition setting and does not depend on females' higher emotional appraisal. Copyright © 2015 the authors 0270-6474/15/350920-16$15.00/0.

  20. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Erica L. Underwood

    2016-01-01

    Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

  1. The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.

    Science.gov (United States)

    Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M; Kerjaschki, Dontscho; Pollak, Daniela D; Uhrin, Pavel; Monje, Francisco J

    2016-12-01

    Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well

  2. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals

    Directory of Open Access Journals (Sweden)

    Rapeli Pekka

    2009-04-01

    Full Text Available Abstract Background Opioid-substitution treatment (OST for opioid dependence (OD has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. Methods Within the first two months (T1 and between 6–9 months (T2 after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. Results Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to

  3. Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.

    Science.gov (United States)

    Duhlin, Amanda; Chen, Yunying; Wermeling, Fredrik; Sedimbi, Saikiran K; Lindh, Emma; Shinde, Rahul; Halaby, Marie Jo; Kaiser, Ylva; Winqvist, Ola; McGaha, Tracy L; Karlsson, Mikael C I

    2016-10-01

    Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

  4. Estradiol-Induced Object Recognition Memory Consolidation Is Dependent on Activation of mTOR Signaling in the Dorsal Hippocampus

    Science.gov (United States)

    Fortress, Ashley M.; Fan, Lu; Orr, Patrick T.; Zhao, Zaorui; Frick, Karyn M.

    2013-01-01

    The mammalian target of rapamycin (mTOR) signaling pathway is an important regulator of protein synthesis and is essential for various forms of hippocampal memory. Here, we asked whether the enhancement of object recognition memory consolidation produced by dorsal hippocampal infusion of 17[Beta]-estradiol (E[subscript 2]) is dependent on mTOR…

  5. Extracting Credible Dependencies for Averaged One-Dependence Estimator Analysis

    Directory of Open Access Journals (Sweden)

    LiMin Wang

    2014-01-01

    Full Text Available Of the numerous proposals to improve the accuracy of naive Bayes (NB by weakening the conditional independence assumption, averaged one-dependence estimator (AODE demonstrates remarkable zero-one loss performance. However, indiscriminate superparent attributes will bring both considerable computational cost and negative effect on classification accuracy. In this paper, to extract the most credible dependencies we present a new type of seminaive Bayesian operation, which selects superparent attributes by building maximum weighted spanning tree and removes highly correlated children attributes by functional dependency and canonical cover analysis. Our extensive experimental comparison on UCI data sets shows that this operation efficiently identifies possible superparent attributes at training time and eliminates redundant children attributes at classification time.

  6. Aging memories: differential decay of episodic memory components.

    Science.gov (United States)

    Talamini, Lucia M; Gorree, Eva

    2012-05-17

    Some memories about events can persist for decades, even a lifetime. However, recent memories incorporate rich sensory information, including knowledge on the spatial and temporal ordering of event features, while old memories typically lack this "filmic" quality. We suggest that this apparent change in the nature of memories may reflect a preferential loss of hippocampus-dependent, configurational information over more cortically based memory components, including memory for individual objects. The current study systematically tests this hypothesis, using a new paradigm that allows the contemporaneous assessment of memory for objects, object pairings, and object-position conjunctions. Retention of each memory component was tested, at multiple intervals, up to 3 mo following encoding. The three memory subtasks adopted the same retrieval paradigm and were matched for initial difficulty. Results show differential decay of the tested episodic memory components, whereby memory for configurational aspects of a scene (objects' co-occurrence and object position) decays faster than memory for featured objects. Interestingly, memory requiring a visually detailed object representation decays at a similar rate as global object recognition, arguing against interpretations based on task difficulty and against the notion that (visual) detail is forgotten preferentially. These findings show that memories undergo qualitative changes as they age. More specifically, event memories become less configurational over time, preferentially losing some of the higher order associations that are dependent on the hippocampus for initial fast encoding. Implications for theories of long-term memory are discussed.

  7. Input-Timing-Dependent Plasticity in the Hippocampal CA2 Region and Its Potential Role in Social Memory.

    Science.gov (United States)

    Leroy, Felix; Brann, David H; Meira, Torcato; Siegelbaum, Steven A

    2017-08-30

    Input-timing-dependent plasticity (ITDP) is a circuit-based synaptic learning rule by which paired activation of entorhinal cortical (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of SC excitation. We now find that paired stimulation of EC and SC inputs also induces ITDP of SC excitation of CA2 PNs. However, whereas CA1 ITDP results from long-term depression of feedforward inhibition (iLTD) as a result of activation of CB1 endocannabinoid receptors on cholecystokinin-expressing interneurons, CA2 ITDP results from iLTD through activation of δ-opioid receptors on parvalbumin-expressing interneurons. Furthermore, whereas CA1 ITDP has been previously linked to enhanced specificity of contextual memory, we find that CA2 ITDP is associated with enhanced social memory. Thus, ITDP may provide a general synaptic learning rule for distinct forms of hippocampal-dependent memory mediated by distinct hippocampal regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats.

    Science.gov (United States)

    Park, Collin R; Zoladz, Phillip R; Conrad, Cheryl D; Fleshner, Monika; Diamond, David M

    2008-04-01

    We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.

  9. Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis.

    Science.gov (United States)

    Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia; Wimmer, Mathieu E; van Tilborg, Erik; Park, Alan J; Poplawski, Shane G; Chung, Caroline W; Havekes, Robbert; Huang, Jiayan; Gatti, Evelina; Pierre, Philippe; Abel, Ted

    2016-04-26

    Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss. These findings collectively demonstrate that 4EBP2-regulated protein synthesis is a critical mediator of the memory deficits caused by sleep deprivation. Copyright © 2016, American Association for the Advancement of Science.

  10. Efficacy and durability of nevirapine in antiretroviral drug naive patients

    NARCIS (Netherlands)

    Lange, Joep M. A.

    2003-01-01

    Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) naive patients. Four key studies have

  11. Selective memory retrieval can impair and improve retrieval of other memories.

    Science.gov (United States)

    Bäuml, Karl-Heinz T; Samenieh, Anuscheh

    2012-03-01

    Research from the past decades has shown that retrieval of a specific memory (e.g., retrieving part of a previous vacation) typically attenuates retrieval of other memories (e.g., memories for other details of the event), causing retrieval-induced forgetting. More recently, however, it has been shown that retrieval can both attenuate and aid recall of other memories (K.-H. T. Bäuml & A. Samenieh, 2010). To identify the circumstances under which retrieval aids recall, the authors examined retrieval dynamics in listwise directed forgetting, context-dependent forgetting, proactive interference, and in the absence of any induced memory impairment. They found beneficial effects of selective retrieval in listwise directed forgetting and context-dependent forgetting but detrimental effects in all the other conditions. Because context-dependent forgetting and listwise directed forgetting arguably reflect impaired context access, the results suggest that memory retrieval aids recall of memories that are subject to impaired context access but attenuates recall in the absence of such circumstances. The findings are consistent with a 2-factor account of memory retrieval and suggest the existence of 2 faces of memory retrieval. 2012 APA, all rights reserved

  12. Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines.

    Science.gov (United States)

    Croft, M; Swain, S L

    1995-05-01

    Development of T cells during primary responses was investigated using pigeon cytochrome C-specific naive Th from TCR transgenic mice. Naive CD4 cells did not activate and help resting B cells. This failure was found to be primarily because the resting B cells were incapable of stimulating the naive Th. Provision of a costimulatory signal such as anti-CD28, or addition of APCs that express costimulatory molecules, such as dendritic cells, activated B cells, and B7+ and B7+ICAM(+)-expressing fibroblasts, induced naive Th activation and promoted T cell-dependent help for IgM secretion. T cell activation for as little as 24 h promoted helper activity, and Ig secretion required production of small amounts of IL-4 by the activated naive Th. On initial stimulation, naive Th secrete only IL-2. By mRNA analysis, activated naive Th were also shown to produce IL-4, however induction of IL-4 message only occurred 24 h after initial activation and required additional stimulation with Ag. A single exposure of naive CD4 to Ag/APC followed by 4 to 12 days in culture led to generation of effector Th which secreted IL-2 and some IFN-gamma, and no detectable IL-4 or IL-5, and which could only help B cells to IgM secretion. In contrast, similar cultures that received Ag/APC one or more times during this period generated effector cells capable of secreting easily detectable titers of IL-4 and IL-5, as well as IL-2 and IFN-gamma, and able to now promote IgG1 and IgE responses. Generation of these Th0-like effectors was accompanied by increasing amounts of IL-4 secreted during the culture period after each restimulation, and addition of anti-IL-4 in culture inhibited development of the capacity to produce Th2 cytokines. These studies reinforce the notion that naive CD4 must interact with a costimulatory professional APC, rather than a resting B cell, for initiation of the primary response, but show that such an interaction can result in rapid development of the ability to interact with

  13. Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis.

    Science.gov (United States)

    Abdelsamed, Hossam A; Moustaki, Ardiana; Fan, Yiping; Dogra, Pranay; Ghoneim, Hazem E; Zebley, Caitlin C; Triplett, Brandon M; Sekaly, Rafick-Pierre; Youngblood, Ben

    2017-06-05

    Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T EM ), and longer-lived central memory (T CM ) and stem cell memory (T SCM ) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T CM and T SCM memory cells resulted in phenotypic conversion into T EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T EM -associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. © 2017 Abdelsamed et al.

  14. Autoimmune Memory T Helper 17 Cell Function and Expansion Are Dependent on Interleukin-23

    Directory of Open Access Journals (Sweden)

    Christopher J. Haines

    2013-05-01

    Full Text Available Interleukin-23 (IL-23 is essential for the differentiation of pathogenic effector T helper 17 (Th17 cells, but its role in memory Th17 cell responses is unclear. Using the experimental autoimmune encephalomyelitis (EAE model, we report that memory Th17 cells rapidly expanded in response to rechallenge and migrated to the CNS in high numbers, resulting in earlier onset and increased severity of clinical disease. Memory Th17 cells were generated from IL-17+ and RORγt+ precursors, and the stability of the Th17 cell phenotype depended on the amount of time allowed for the primary response. IL-23 was required for this enhanced recall response. IL-23 receptor blockade did not directly impact IL-17 production, but did impair the subsequent proliferation and generation of effectors coexpressing the Th1 cell-specific transcription factor T-bet. In addition, many genes required for cell-cycle progression were downregulated in Th17 cells that lacked IL-23 signaling, showing that a major mechanism for IL-23 in primary and memory Th17 cell responses operates via regulation of proliferation-associated pathways.

  15. Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

    Science.gov (United States)

    Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

    2018-04-23

    Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

  16. Naive (commonsense) geography and geobrowser usability after ten years of Google Earth

    Science.gov (United States)

    Hamerlinck, J. D.

    2016-04-01

    In 1995, the concept of ‘naive geography’ was formally introduced as an area of cognitive geographic information science representing ‘the body of knowledge that people have about the surrounding geographic world’ and reflecting ‘the way people think and reason about geographic space and time, both consciously and subconsciously’. The need to incorporate such commonsense knowledge and reasoning into design of geospatial technologies was identified but faced challenges in formalizing these relationships and processes in software implementation. Ten years later, the Google Earth geobrowser was released, marking the beginning of a new era of open access to, and application of, geographic data and information in society. Fast-forward to today, and the opportunity presents itself to take stock of twenty years of naive geography and a decade of the ubiquitous virtual globe. This paper introduces an ongoing research effort to explore the integration of naive (or commonsense) geography concepts in the Google Earth geobrowser virtual globe and their possible impact on Google Earth's usability, utility, and usefulness. A multi-phase methodology is described, combining usability reviews and usability testing with use-case scenarios involving the U.S.-Canadian Yellowstone to Yukon Initiative. Initial progress on a usability review combining cognitive walkthroughs and heuristics evaluation is presented.

  17. Three Naive Questions: Addressed to the Modern Educational Optimism

    Science.gov (United States)

    Krstic, Predrag

    2016-01-01

    This paper aims to question anew the popular and supposedly self-evident affirmation of education, in its modern incarnation as in its historical notion. The "naive" questions suggest that we have recently taken for granted that education ought to be for the masses, that it ought to be upbringing, and that it is better than ignorance.…

  18. Context-dependent memory under stressful conditions: the case of skydiving.

    Science.gov (United States)

    Thompson, L A; Williams, K L; L'Esperance, P; Cornelius, J

    2001-01-01

    Two experiments examined the effect of differing levels of emotional arousal on learning and memory for words in matching and mismatching contexts. In Experiment 1, experienced skydivers learned words either in the air or on the ground and recalled them in the same context or in the other context. Experiment 2 replicated the stimuli and design of the first experiment except that participants were shown a skydiving video in lieu of skydiving. Recall was poor in air-learning conditions with actual skydiving, but when lists were learned on land, recall was higher in the matching context than in the mismatching context. In the skydiving video experiment, recall was higher in matching learn-recall contexts regardless of the situation in which learning occurred. We propose that under extremely emotionally arousing circumstances, environmental and/or mood cues are unlikely to become encoded or linked to newly acquired information and thus cannot serve as cues to retrieval. Results can be applied to understanding variations in context-dependent memory in occupations (e.g., police, military special operations, and Special Weapons and Tactics teams) in which the worker experiences considerable emotional stress while learning or recalling new information.

  19. Factors that Determine the Non-Linear Amygdala Influence on Hippocampus-Dependent Memory

    OpenAIRE

    Akirav, Irit; Richter-Levin, Gal

    2006-01-01

    Stressful experiences are known to either improve or impair hippocampal-dependent memory tasks and synaptic plasticity. These positive and negative effects of stress on the hippocampus have been largely documented, however little is known about the mechanism involved in the twofold influence of stress on hippocampal functioning and about what factors define an enhancing or inhibitory outcome. We have recently demonstrated that activation of the basolateral amygdala can produce a biphasic effe...

  20. Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

    Science.gov (United States)

    Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

    2015-01-01

    Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

  1. Naive forecasting: the fiasco of coal gasification

    Energy Technology Data Exchange (ETDEWEB)

    Peirce, W S

    1985-01-01

    The decision by the U.S. government to subsidize the development of coal gasification was based on a naive forecast that neglected the influence of price on both conventional sources of supply and consumer demand. Even before substantial construction costs were incurred on the Great Plains plant, a surplus of natural gas has developed. The political process, however, did not include the sort of critical review that often accompanies the financing decision in the private sector and that would surely have prevented this error. 17 references.

  2. CD4-dependent characteristics of coreceptor use and HIV type 1 V3 sequence in a large population of therapy-naive individuals.

    Science.gov (United States)

    Low, Andrew J; Marchant, David; Brumme, Chanson J; Brumme, Zabrina L; Dong, Winnie; Sing, Tobias; Hogg, Robert S; Montaner, Julio S G; Gill, Vikram; Cheung, Peter K; Harrigan, P Richard

    2008-02-01

    We investigated the associations between coreceptor use, V3 loop sequence, and CD4 count in a cross-sectional analysis of a large cohort of chronically HIV-infected, treatment-naive patients. HIV coreceptor usage was determined in the last pretherapy plasma sample for 977 individuals initiating HAART in British Columbia, Canada using the Monogram Trofile Tropism assay. Relative light unit (RLU) readouts from the Trofile assay, as well as HIV V3 loop sequence data, were examined as a function of baseline CD4 cell count for 953 (97%) samples with both phenotype and genotype data available. Median CCR5 RLUs were high for both R5 and X4-capable samples, while CXCR4 RLUs were orders of magnitude lower for X4 samples (p < 0.001). CCR5 RLUs in R5 samples (N = 799) increased with decreasing CD4 count (p < 0.001), but did not vary with plasma viral load (pVL) (p = 0.74). In X4 samples (N = 178), CCR5 RLUs decreased with decreasing CD4 count (p = 0.046) and decreasing pVL (p = 0.097), while CXCR4 RLUs increased with decreasing pVL (p = 0.0008) but did not vary with CD4 (p = 0.96). RLUs varied with the presence of substitutions at V3 loop positions 11, 25, and 6-8. The prevalence and impact of substitutions at codons 25 and 6-8 were CD4 dependent as was the presence of amino acid mixtures in the V3; substitutions at position 11 were CD4 independent. Assay RLU measures predictably vary with both immunological and virological parameters. The ability to predict X4 virus using genotypic determinants at positions 25 and 6-8 of the V3 loop is CD4 dependent, while position 11 appears to be CD4 independent.

  3. Spike-timing dependent plasticity in a transistor-selected resistive switching memory

    International Nuclear Information System (INIS)

    Ambrogio, S; Balatti, S; Nardi, F; Facchinetti, S; Ielmini, D

    2013-01-01

    In a neural network, neuron computation is achieved through the summation of input signals fed by synaptic connections. The synaptic activity (weight) is dictated by the synchronous firing of neurons, inducing potentiation/depression of the synaptic connection. This learning function can be supported by the resistive switching memory (RRAM), which changes its resistance depending on the amplitude, the pulse width and the bias polarity of the applied signal. This work shows a new synapse circuit comprising a MOS transistor as a selector and a RRAM as a variable resistance, displaying spike-timing dependent plasticity (STDP) similar to the one originally experienced in biological neural networks. We demonstrate long-term potentiation and long-term depression by simulations with an analytical model of resistive switching. Finally, the experimental demonstration of the new STDP scheme is presented. (paper)

  4. Effects of working memory load, a history of conduct disorder, and sex on decision making in substance dependent individuals.

    Science.gov (United States)

    Fridberg, Daniel J; Gerst, Kyle R; Finn, Peter R

    2013-12-01

    Substance dependence and antisocial psychopathology, such as a history of childhood conduct disorder (HCCD), are associated with impulsive or disadvantageous decision making and reduced working memory capacity (WMC). Reducing WMC via a working memory load increases disadvantageous decision making in healthy adults, but no previous studies have examined this effect in young adults with substance dependence and HCCD. Young adults with substance dependence (SubDep; n=158, 71 female), substance dependence and HCCD (SubDep+HCCD; n=72, 24 female), and control participants (n=152, 84 female) completed a test of decision making (the Iowa Gambling Task; IGT) with or without a concurrent working memory load intended to tax WMC. Outcomes were (i) net advantageous decisions on the IGT, and (ii) preferences for infrequent- versus frequent-punishment decks. SubDep+HCCD men made fewer advantageous decisions on the IGT than control men without a load, but there were no group differences among women in that condition. Load was associated with fewer advantageous decisions for SubDep+HCCD women and control men, but not for men or women in the other groups. Participants showed greater preference for infrequent-punishment, advantageous decks under load as well. There are gender differences in the effects of substance dependence, HCCD, and working memory load on decision making on the IGT. Decision making by control men and SubDep+HCCD women suffered the most under load. Load increases preferences for less-frequent punishments, similar to a delay discounting effect. Future research should clarify the cognitive and neural mechanisms underlying these effects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Environmental context effects on episodic memory are dependent on retrieval mode and modulated by neuropsychological status.

    Science.gov (United States)

    Barak, Ohr; Vakil, Eli; Levy, Daniel A

    2013-01-01

    Contextual change or constancy between occasions of memory formation and retrieval are commonly assumed to affect retrieval success, yet such effects may be inconsistent, and the processes leading to the pattern of effects are still not well understood. We conducted a systematic investigation of environmental context effects on memory, using a range of materials (common objects, pictures of familiar and unfamiliar faces, words, and sentences), and four types of retrieval (free recall, cued recall, recognition, and order memory), all assessed within participants. Additionally, we examined the influence of mnemonic challenge on context effects by examining both healthy participants and a group of patients in rehabilitation following traumatic brain injury (TBI). We found no effects of contextual factors on tests of recognition for either group of participants, but effects did emerge for cued and free recall, with the most prominent effects being on memory for objects. Furthermore, while patients' memory abilities in general were impaired relative to the comparison group, they exhibited greater influences of contextual reinstatement on several recall tasks. These results support suggestions that environmental context effects on memory are dependent on retrieval mode and on the extent to which retrieval is challenging because of neurocognitive status. Additionally, findings of environmental context effects in memory-impaired TBI patients suggest that by harnessing such preserved indirect memory (e.g., using reminder technologies), it may be possible to ameliorate TBI patients' difficulties in explicit remembering.

  6. Protein phosphatase dependent circadian regulation of intermediate-term associative memory

    OpenAIRE

    Michel, Maximilian; Gardner, Jacob S.; Green, Charity L.; Organ, Chelsea L.; Lyons, Lisa C.

    2013-01-01

    The endogenous circadian clock is a principal factor modulating memory across species. Determining the processes through which the circadian clock modulates memory formation is a key issue in understanding and identifying mechanisms to improve memory. We used the marine mollusk Aplysia californica to investigate circadian modulation of intermediate-term memory (ITM) and the mechanisms through which the circadian clock phase specifically suppresses memory using the operant learning paradigm, l...

  7. Results of the naive quark model

    International Nuclear Information System (INIS)

    Gignoux, C.

    1987-10-01

    The hypotheses and limits of the naive quark model are recalled and results on nucleon-nucleon scattering and possible multiquark states are presented. Results show that with this model, ropers do not come. For hadron-hadron interactions, the model predicts Van der Waals forces that the resonance group method does not allow. Known many-body forces are not found in the model. The lack of mesons shows up in the absence of a far reaching force. However, the model does have strengths. It is free from spuriousness of center of mass, and allows a democratic handling of flavor. It has few parameters, and its predictions are very good [fr

  8. CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals.

    Science.gov (United States)

    Do, Jeong-Su; Visperas, Anabelle; O'Brien, Rebecca L; Min, Booki

    2012-04-01

    A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)β1-dependent mechanism, thus considered 'innate' IL-17-producing cells. Here, we report that γδ T cells generated within αβ T cell (or CD4 T cell)-deficient environments displayed altered cytokine profiles; particularly, 'innate' IL-17 expression was significantly impaired compared with those in wild-type mice. Impaired IL-17 production in γδ T cells was directly related to CD4 T-cell deficiency, because depletion of CD4 T cells in wild-type mice diminished and adoptive CD4 T-cell transfer into T-cell receptor β-/- mice restored IL-17 expression in γδ T cells. CD4 T cell-mediated IL-17 expression required TGFβ1. Moreover, Th17 but not Th1 or Th2 effector CD4 T cells were highly efficient in enhancing γδ T-cell IL-17 expression. Taken together, our results highlight a novel CD4 T cell-dependent mechanism that shapes the generation of IL-17+ γδ T cells in naive settings.

  9. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.

    Science.gov (United States)

    Iyer, Smita S; Chatraw, Janel Hart; Tan, Wendy G; Wherry, E John; Becker, Todd C; Ahmed, Rafi; Kapasi, Zoher F

    2012-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.

  10. CD4 T cell autophagy is integral to memory maintenance.

    Science.gov (United States)

    Murera, Diane; Arbogast, Florent; Arnold, Johan; Bouis, Delphine; Muller, Sylviane; Gros, Frédéric

    2018-04-13

    Studies of mice deficient for autophagy in T cells since thymic development, concluded that autophagy is integral to mature T cell homeostasis. Basal survival and functional impairments in vivo, limited the use of these models to delineate the role of autophagy during the immune response. We generated Atg5 f/f distal Lck (dLck)-cre mice, with deletion of autophagy only at a mature stage. In this model, autophagy deficiency impacts CD8 + T cell survival but has no influence on CD4 + T cell number and short-term activation. Moreover, autophagy in T cells is dispensable during early humoral response but critical for long-term antibody production. Autophagy in CD4 + T cells is required to transfer humoral memory as shown by injection of antigen-experienced cells in naive mice. We also observed a selection of autophagy-competent cells in the CD4 + T cell memory compartment. We performed in vitro differentiation of memory CD4 + T cells, to better characterize autophagy-deficient memory cells. We identified mitochondrial and lipid load defects in differentiated memory CD4 + T cells, together with a compromised survival, without any collapse of energy production. We then propose that memory CD4 + T cells rely on autophagy for their survival to regulate toxic effects of mitochondrial activity and lipid overload.

  11. The naive CD4+ count in HIV-1-infected patients at time of initiation of highly active antiretroviral therapy is strongly associated with the level of immunological recovery

    DEFF Research Database (Denmark)

    Michael, OG; Kirk, O; Mathiesen, Lars Reinhardt

    2002-01-01

    CD4 + count followed a triphasic pattern, reflecting an initial phase of rapid redistribution from lymphoid tissues, followed by a slow increase, partially due to an increase in naive CD4+ cell count. From Month 18 onwards, both naive and total CD4 + cell counts stabilized, although viral suppression......-infected patients. The focus was on the naive CD4 + cell time course and associations between naive CD4 + cell counts and established prognostic markers. Total and naive CD4 + cell counts were measured using flow cytometry. The HIV-RNA detection limit was 20 copies/ml. During 36 months of HAART, the total...... was sustained. There was no association between plasma viral load and the increase in naive CD4 + cell count. Importantly, baseline naive CD4 + cell count was significantly associated with the change in naive CD4 + cell count, suggesting that the naive cell count at baseline does influence the immunological...

  12. Binary naive Bayesian classifiers for correlated Gaussian features: a theoretical analysis

    CSIR Research Space (South Africa)

    Van Dyk, E

    2008-11-01

    Full Text Available classifier with Gaussian features while using any quadratic decision boundary. Therefore, the analysis is not restricted to Naive Bayesian classifiers alone and can, for instance, be used to calculate the Bayes error performance. We compare the analytical...

  13. Expert and Naive Raters Using the PAG: Does it Matter?

    Science.gov (United States)

    Cornelius, Edwin T.; And Others

    1984-01-01

    Questions the observed correlation between job experts and naive raters using the Position Analysis Questionnaire (PAQ); and conducts a replication of the Smith and Hakel study (1979) with college students (N=39). Concluded that PAQ ratings from job experts and college students are not equivalent and therefore are not interchangeable. (LLL)

  14. Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

    Science.gov (United States)

    Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

    2017-10-01

    Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

  15. Stress Effects on Working Memory, Explicit Memory, and Implicit Memory for Neutral and Emotional Stimuli in Healthy Men

    OpenAIRE

    Luethi, Mathias; Meier, Beat; Sandi, Carmen

    2009-01-01

    Stress is a strong modulator of memory function. However, memory is not a unitary process and stress seems to exert different effects depending on the memory type under study. Here, we explored the impact of social stress on different aspects of human memory, including tests for explicit memory and working memory (for neutral materials), as well as implicit memory (perceptual priming, contextual priming and classical conditioning for emotional stimuli). A total of 35 young adult...

  16. Context-dependent activation of reduced autobiographical memory specificity as an avoidant coping style.

    Science.gov (United States)

    Debeer, Elise; Raes, Filip; Williams, J Mark G; Hermans, Dirk

    2011-12-01

    According to the affect-regulation hypothesis (Williams et al., 2007), reduced autobiographical memory specificity (rAMS) or overgeneral memory (OGM) might be considered a cognitive avoidance strategy; that is, people learn to avoid the emotionally painful consequences associated with the retrieval of specific negative memories. Based on this hypothesis, one would predict significant negative associations between AMS and avoidant coping. However, studies investigating this prediction have led to equivocal results. In the present study we tested a possible explanation for these contradictory findings. It was hypothesized that rAMS (in part) reflects an avoidant coping strategy, which might only become apparent under certain conditions, that is, conditions that signal the possibility of 'danger.' To test this hypothesis, we assessed AMS and behavioral avoidance but experimentally manipulated the instructions. In the neutral condition, two parallel versions of the Autobiographical Memory Test (AMT) were presented under neutral instructions. In the threat condition, the first AMT was presented under neutral instructions, while the second AMT was presented under 'threat instructions.' Results showed no significant correlations between avoidance and OGM under neutral conditions but significant and markedly stronger correlations under threat conditions, with more avoidance being associated with fewer specific and more categoric memories. In addition, high avoiders showed a stronger reduction in AMS in the threat condition as compared with the neutral condition, while low avoiders showed no such difference between conditions. The data confirm that OGM can be considered as part of a broader avoidant coping style. However, more importantly, they show that, at least in nonclinical individuals, the activation of this coping style may depend on the context. (c) 2011 APA, all rights reserved.

  17. Identification of a dopamine receptor-mediated opiate reward memory switch in the basolateral amygdala-nucleus accumbens circuit.

    Science.gov (United States)

    Lintas, Alessandra; Chi, Ning; Lauzon, Nicole M; Bishop, Stephanie F; Gholizadeh, Shervin; Sun, Ninglei; Tan, Huibing; Laviolette, Steven R

    2011-08-03

    The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-state-dependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.

  18. Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice.

    Science.gov (United States)

    Yang, Liya; Zou, Bende; Xiong, Xiaoxing; Pascual, Conrado; Xie, James; Malik, Adam; Xie, Julian; Sakurai, Takeshi; Xie, Xinmin Simon

    2013-03-20

    Hypocretin/orexin (Hcrt)-producing neurons in the lateral hypothalamus project throughout the brain, including to the hippocampus, where Hcrt receptors are widely expressed. Hcrt neurons activate these targets to orchestrate global arousal state, wake-sleep architecture, energy homeostasis, stress adaptation, and reward behaviors. Recently, Hcrt has been implicated in cognitive functions and social interaction. In the present study, we tested the hypothesis that Hcrt neurons are critical to social interaction, particularly social memory, using neurobehavioral assessment and electrophysiological approaches. The validated "two-enclosure homecage test" devices and procedure were used to test sociability, preference for social novelty (social novelty), and recognition memory. A conventional direct contact social test was conducted to corroborate the findings. We found that adult orexin/ataxin-3-transgenic (AT) mice, in which Hcrt neurons degenerate by 3 months of age, displayed normal sociability and social novelty with respect to their wild-type littermates. However, AT mice displayed deficits in long-term social memory. Nasal administration of exogenous Hcrt-1 restored social memory to an extent in AT mice. Hippocampal slices taken from AT mice exhibited decreases in degree of paired-pulse facilitation and magnitude of long-term potentiation, despite displaying normal basal synaptic neurotransmission in the CA1 area compared to wild-type hippocampal slices. AT hippocampi had lower levels of phosphorylated cAMP response element-binding protein (pCREB), an activity-dependent transcription factor important for synaptic plasticity and long-term memory storage. Our studies demonstrate that Hcrt neurons play an important role in the consolidation of social recognition memory, at least in part through enhancements of hippocampal synaptic plasticity and cAMP response element-binding protein phosphorylation.

  19. CD49b-dependent establishment of T helper cell memory.

    Science.gov (United States)

    Hanazawa, Asami; Hayashizaki, Koji; Shinoda, Kenta; Yagita, Hideo; Okumura, Ko; Löhning, Max; Hara, Takahiro; Tani-ichi, Shizue; Ikuta, Koichi; Eckes, Beate; Radbruch, Andreas; Tokoyoda, Koji; Nakayama, Toshinori

    2013-09-01

    CD4 T cells play a key role in immunological memory. We have demonstrated that professional memory CD4 T cells reside and rest in the bone marrow (BM). However, the molecular mechanisms of their establishment in the BM and their maintenance remain unclear. We here show that memory CD4 T cells express high levels of CD49b and that CD49b-deficient or -blocked memory CD4 T-cell precursors fail to migrate from blood into the marrow of the bone, and they especially fail to transmigrate through sinusoidal endothelial cells of the BM. In the marrow, memory CD4 T cells and the precursors contact stromal cells expressing collagen II that are specific ligands for CD49b. Interestingly, memory CD4 T cells on day 117 of an immune response also dock on IL-7(+)/collagen XI(+) stromal cells, whereas memory precursors on day 12 do not. These results indicate that the collagen receptor CD49b is required for the migration of memory CD4 T-cell precursors into their survival niches of the bone marrow.

  20. Executed Movement Using EEG Signals through a Naive Bayes Classifier

    Directory of Open Access Journals (Sweden)

    Juliano Machado

    2014-11-01

    Full Text Available Recent years have witnessed a rapid development of brain-computer interface (BCI technology. An independent BCI is a communication system for controlling a device by human intension, e.g., a computer, a wheelchair or a neuroprosthes is, not depending on the brain’s normal output pathways of peripheral nerves and muscles, but on detectable signals that represent responsive or intentional brain activities. This paper presents a comparative study of the usage of the linear discriminant analysis (LDA and the naive Bayes (NB classifiers on describing both right- and left-hand movement through electroencephalographic signal (EEG acquisition. For the analysis, we considered the following input features: the energy of the segments of a band pass-filtered signal with the frequency band in sensorimotor rhythms and the components of the spectral energy obtained through the Welch method. We also used the common spatial pattern (CSP filter, so as to increase the discriminatory activity among movement classes. By using the database generated by this experiment, we obtained hit rates up to 70%. The results are compatible with previous studies.

  1. Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

    Science.gov (United States)

    Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

    2012-11-30

    Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.

    Science.gov (United States)

    Zhu, Xueling; Wang, Xiang; Xiao, Jin; Liao, Jian; Zhong, Mingtian; Wang, Wei; Yao, Shuqiao

    2012-04-01

    Imaging studies have shown that major depressive disorder (MDD) is associated with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and MDD-related pathopsychological characteristics, such as depressive rumination and overgeneral autobiographical memory (OGM) phenomena, still remain unclear. Using independent component analysis, we analyzed resting-state functional magnetic resonance imaging data obtained from 35 first-episode, treatment-naive young adults with MDD and from 35 matched healthy control subjects. Patients with MDD exhibited higher levels of rumination and OGM than did the control subjects. We observed increased functional connectivity in the anterior medial cortex regions (especially the medial prefrontal cortex and anterior cingulate cortex) and decreased functional connectivity in the posterior medial cortex regions (especially the posterior cingulate cortex/precuneus) in MDD patients compared with control subjects. In the depressed group, the increased functional connectivity in the anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in the posterior medial cortex correlated negatively with OGM score. We report dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Increased functional connectivity in anterior medial regions of the resting-state DMN was associated with rumination, whereas decreased functional connectivity in posterior medial regions was associated with OGM. These results provide new evidence for the importance of the DMN in the pathophysiology of MDD and suggest that abnormal DMN activity may be an MDD trait. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Creating opioid dependence in the emergency department.

    Science.gov (United States)

    Upadhye, Suneel

    2018-01-01

    Clinical question What is the risk of creating opioid dependence from an ED opioid prescription? Article chosen Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017;376:663-73, doi:10.1056/NEJMsa1610524. This study examined the risk of creating long-term opioid dependence from a prescription written in an opioid-naive patient in the ED.

  4. Visual perception is dependent on visuospatial working memory and thus on the posterior parietal cortex.

    Science.gov (United States)

    Pisella, Laure

    2017-06-01

    Visual perception involves complex and active processes. We will start by explaining why visual perception is dependent on visuospatial working memory, especially the spatiotemporal integration of the perceived elements through the ocular exploration of visual scenes. Then we will present neuropsychology, transcranial magnetic stimulation and neuroimaging data yielding information on the specific role of the posterior parietal cortex of the right hemisphere in visuospatial working memory. Within the posterior parietal cortex, neuropsychology data also suggest that there might be dissociated neural substrates for deployment of attention (superior parietal lobules) and spatiotemporal integration (right inferior parietal lobule). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Memory-dependent derivatives for photothermal semiconducting medium in generalized thermoelasticity with two-temperature

    Science.gov (United States)

    Lotfy, K.; Sarkar, N.

    2017-11-01

    In this work, a novel generalized model of photothermal theory with two-temperature thermoelasticity theory based on memory-dependent derivative (MDD) theory is performed. A one-dimensional problem for an elastic semiconductor material with isotropic and homogeneous properties has been considered. The problem is solved with a new model (MDD) under the influence of a mechanical force with a photothermal excitation. The Laplace transform technique is used to remove the time-dependent terms in the governing equations. Moreover, the general solutions of some physical fields are obtained. The surface taken into consideration is free of traction and subjected to a time-dependent thermal shock. The numerical Laplace inversion is used to obtain the numerical results of the physical quantities of the problem. Finally, the obtained results are presented and discussed graphically.

  6. Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event.

    Science.gov (United States)

    Contestabile, Antonio; Peña-Altamira, Emiliano; Virgili, Marco; Monti, Barbara

    2016-06-01

    Zinc is a trace element important for synaptic plasticity, learning and memory. Zinc deficiency, both during pregnancy and after birth, impairs cognitive performance and, in addition to memory deficits, also results in alterations of attention, activity, neuropsychological behavior and motor development. The effects of zinc supplementation on cognition, particularly in the adult, are less clear. We demonstrate here in adult rats, that 4 week-long zinc supplementation given by drinking water, and approximately doubling normal daily intake, strongly impairs consolidation of hippocampal-dependent memory, tested through contextual fear conditioning and inhibitory avoidance. Furthermore, the same treatment started after memory consolidation of training for the same behavioral tests, substantially dampens the recall of the stressful event occurred 4 weeks before. A molecular correlate of the amnesic effect of zinc supplementation is represented by a dysregulated function of GSK-3ß in the hippocampus, a kinase that participates in memory processes. The possible relevance of these data for humans, in particular regarding post-traumatic stress disorders, is discussed in view of future investigation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  7. Associations between vascular co-morbidities and depression in insulin-naive diabetes patients

    DEFF Research Database (Denmark)

    Koopmans, B; Pouwer, F; de Bie, Rob A

    2009-01-01

    AIMS/HYPOTHESIS: The aim of the study was to determine the prevalence of depression in insulin-naive diabetes patients and to investigate the associations between different forms of vascular co-morbidity and depression. METHODS: Cross-sectional data were used from a primary-care sample of 1......,269 insulin-naive (i.e. not using insulin therapy) diabetes patients participating in the DIAZOB Primary Care Diabetes study. Demographics, vascular co-morbidities, clinical and lifestyle characteristics, and psychosocial factors were assessed. Depression symptoms were measured with the Edinburgh Depression.......2% vs 10.0%). Single vascular co-morbidities were not associated with increased rates of depression. The final model predicting depression included: having multiple vascular co-morbidities compared with none; having less social support; having experienced a recent stressful life event; female sex...

  8. 1Protein Energy Malnutrition Impairs Homeostatic Proliferation of Memory CD8 T cells

    Science.gov (United States)

    Iyer, Smita S.; Chatraw, Janel Hart; Tan, Wendy G.; Wherry, E. John; Becker, Todd C.; Ahmed, Rafi; Kapasi, Zoher F.

    2011-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. Here we show that protein energy malnutrition (PEM) induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate-protein (AP) fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV) immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that PEM caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. While antigen-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less-responsive to poly(I:C)-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13 resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals. PMID:22116826

  9. Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation.

    Science.gov (United States)

    Beilharz, J E; Maniam, J; Morris, M J

    2016-06-01

    Chronic high-energy diets are known to induce obesity and impair memory; these changes have been associated with inflammation in brain areas crucial for memory. In this study, we investigated whether inflammation could also be related to diet-induced memory deficits, prior to obesity. We exposed rats to chow, chow supplemented with a 10% sucrose solution (Sugar) or a diet high in fat and sugar (Caf+Sugar) and assessed hippocampal-dependent and perirhinal-dependent memory at 1 week. Both high-energy diet groups displayed similar, selective hippocampal-dependent memory deficits despite the Caf+Sugar rats consuming 4-5 times more energy, and weighing significantly more than the other groups. Extreme weight gain and excessive energy intake are therefore not necessary for deficits in memory. Weight gain across the diet period however, was correlated with the memory deficits, even in the Chow rats. The Sugar rats had elevated expression of a number of inflammatory genes in the hippocampus and WAT compared to Chow and Caf+Sugar rats but not in the perirhinal cortex or hypothalamus. Blood glucose concentrations were also elevated in the Sugar rats, and were correlated with the hippocampal inflammatory markers. Together, these results indicate that liquid sugar can rapidly elevate markers of central and peripheral inflammation, in association with hyperglycemia, and this may be related to the memory deficits in the Sugar rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline.

    Science.gov (United States)

    Mahoney, James J; Jackson, Brian J; Kalechstein, Ari D; De La Garza, Richard; Newton, Thomas F

    2011-03-30

    Abstinent methamphetamine (Meth) dependent individuals demonstrate poorer performance on tests sensitive to attention/information processing speed, learning and memory, and working memory when compared to non-Meth dependent individuals. The poorer performance on these tests may contribute to the morbidity associated with Meth-dependence. In light of this, we sought to determine the effects of acute, low-dose Meth administration on attention, working memory, and verbal learning and memory in 19 non-treatment seeking, Meth-dependent individuals. Participants were predominantly male (89%), Caucasian (63%), and cigarette smokers (63%). Following a four day, drug-free washout period, participants were given a single-blind intravenous infusion of saline, followed the next day by 30 mg of Meth. A battery of neurocognitive tasks was administered before and after each infusion, and performance on measures of accuracy and reaction time were compared between conditions. While acute Meth exposure did not affect test performance for the entire sample, participants who demonstrated relatively poor performance on these tests at baseline, identified using a median split on each test, showed significant improvement on measures of attention/information processing speed and working memory when administered Meth. Improved performance was seen on the following measures of working memory: choice reaction time task (p≤0.04), a 1-back task (p≤0.01), and a 2-back task (p≤0.04). In addition, those participants demonstrating high neurocognitive performance at baseline experienced similar or decreased performance following Meth exposure. These findings suggest that acute administration of Meth may temporarily improve Meth-associated neurocognitive performance in those individuals experiencing lower cognitive performance at baseline. As a result, stimulants may serve as a successful treatment for improving cognitive functioning in those Meth-dependent individuals experiencing

  11. Temperature dependent evolution of wrinkled single-crystal silicon ribbons on shape memory polymers.

    Science.gov (United States)

    Wang, Yu; Yu, Kai; Qi, H Jerry; Xiao, Jianliang

    2017-10-25

    Shape memory polymers (SMPs) can remember two or more distinct shapes, and thus can have a lot of potential applications. This paper presents combined experimental and theoretical studies on the wrinkling of single-crystal Si ribbons on SMPs and the temperature dependent evolution. Using the shape memory effect of heat responsive SMPs, this study provides a method to build wavy forms of single-crystal silicon thin films on top of SMP substrates. Silicon ribbons obtained from a Si-on-insulator (SOI) wafer are released and transferred onto the surface of programmed SMPs. Then such bilayer systems are recovered at different temperatures, yielding well-defined, wavy profiles of Si ribbons. The wavy profiles are shown to evolve with time, and the evolution behavior strongly depends on the recovery temperature. At relatively low recovery temperatures, both wrinkle wavelength and amplitude increase with time as evolution progresses. Finite element analysis (FEA) accounting for the thermomechanical behavior of SMPs is conducted to study the wrinkling of Si ribbons on SMPs, which shows good agreement with experiment. Merging of wrinkles is observed in FEA, which could explain the increase of wrinkle wavelength observed in the experiment. This study can have important implications for smart stretchable electronics, wrinkling mechanics, stimuli-responsive surface engineering, and advanced manufacturing.

  12. Episodic memory, semantic memory, and amnesia.

    Science.gov (United States)

    Squire, L R; Zola, S M

    1998-01-01

    Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.

  13. Working memory, long-term memory, and medial temporal lobe function

    Science.gov (United States)

    Jeneson, Annette; Squire, Larry R.

    2012-01-01

    Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance in patients with MTL lesions on tasks with short retention intervals, or no retention interval, and neuroimaging findings with similar tasks have been interpreted to mean that the MTL is sometimes needed for working memory and possibly even for visual perception itself. We present a reappraisal of this interpretation. Our main conclusion is that, if the material to be learned exceeds working memory capacity, if the material is difficult to rehearse, or if attention is diverted, performance depends on long-term memory even when the retention interval is brief. This fundamental notion is better captured by the terms subspan memory and supraspan memory than by the terms short-term memory and long-term memory. We propose methods for determining when performance on short-delay tasks must depend on long-term (supraspan) memory and suggest that MTL lesions impair performance only when immediate memory and working memory are insufficient to support performance. In neuroimaging studies, MTL activity during encoding is influenced by the memory load and correlates positively with long-term retention of the material that was presented. The most parsimonious and consistent interpretation of all the data is that subspan memoranda are supported by immediate memory and working memory and are independent of the MTL. PMID:22180053

  14. Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

    Science.gov (United States)

    Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

    2015-02-24

    The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

  15. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

    Directory of Open Access Journals (Sweden)

    Vafaei A.L.

    2008-03-01

    Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

  16. Item-location binding in working memory: is it hippocampus-dependent?

    Science.gov (United States)

    Allen, Richard J; Vargha-Khadem, Faraneh; Baddeley, Alan D

    2014-07-01

    A general consensus is emerging that the hippocampus has an important and active role in the creation of new long-term memory representations of associations or bindings between elements. However, it is less clear whether this contribution can be extended to the creation of temporary bound representations in working memory, involving the retention of small numbers of items over short delays. We examined this by administering a series of recognition and recall tests of working memory for colour-location binding and object-location binding to a patient with highly selective hippocampal damage (Jon), and groups of control participants. Jon achieved high levels of accuracy in all working memory tests of recognition and recall binding across retention intervals of up to 10s. In contrast, Jon performed at chance on an unexpected delayed test of the same object-location binding information. These findings indicate a clear dissociation between working memory and long-term memory, with no evidence for a critical hippocampal contribution to item-location binding in working memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Analog memory and spike-timing-dependent plasticity characteristics of a nanoscale titanium oxide bilayer resistive switching device

    International Nuclear Information System (INIS)

    Seo, Kyungah; Park, Sangsu; Lee, Kwanghee; Lee, Byounghun; Hwang, Hyunsang; Kim, Insung; Jung, Seungjae; Jo, Minseok; Park, Jubong; Shin, Jungho; Biju, Kuyyadi P; Kong, Jaemin

    2011-01-01

    We demonstrated analog memory, synaptic plasticity, and a spike-timing-dependent plasticity (STDP) function with a nanoscale titanium oxide bilayer resistive switching device with a simple fabrication process and good yield uniformity. We confirmed the multilevel conductance and analog memory characteristics as well as the uniformity and separated states for the accuracy of conductance change. Finally, STDP and a biological triple model were analyzed to demonstrate the potential of titanium oxide bilayer resistive switching device as synapses in neuromorphic devices. By developing a simple resistive switching device that can emulate a synaptic function, the unique characteristics of synapses in the brain, e.g. combined memory and computing in one synapse and adaptation to the outside environment, were successfully demonstrated in a solid state device.

  18. Lipid Profile of Anti Retroviral Treatment Naive HIV Infected Patients ...

    African Journals Online (AJOL)

    hypercholesterolemia [22.4% (22/98) vs. 10.4% (11/106), P = 0.02]. Lower HDL.C was associated with CD4+ cell count < 200 cells/ƒÊL (P = 0.02). Conclusion: Lipid abnormalities are common in treatment.naive HIV.infected patients even in the absence of major host.related risk factors for dyslipidemia. HIV.infected patients ...

  19. A Workshop for High School Students on Naive Set Theory

    Science.gov (United States)

    Wegner, Sven-Ake

    2014-01-01

    In this article we present the prototype of a workshop on naive set theory designed for high school students in or around the seventh year of primary education. Our concept is based on two events which the author organized in 2006 and 2010 for students of elementary school and high school, respectively. The article also includes a practice report…

  20. Induction of latent memory for conditioned food aversion and its transformation into "active" state depend on translation and transcription processes.

    Science.gov (United States)

    Solntseva, S V; Nikitin, V P

    2014-05-01

    Mechanisms of induction and retrieval of latent (hidden) memory for conditioned food aversion were investigated in snails. After initial training (single combination of a food stimulus with electric shock), aversive reactions to presentation of the conditioned food stimulus were not revealed. Repeated presentation of the stimuli in 12 days after the first combination was followed by the appearance of aversive food reactions that persisted for at least 14 days. Injections of inhibitors of protein (cycloheximide) or RNA (α-amanitin) synthesis immediately after the first or second combined presentation of the stimuli disturbed skill performance. We hypothesized that single combination of food and reinforcing stimuli led to translation- and transcription-dependent induction of latent conditioned food aversion memory. Transformation of this memory into an active state after repeated presentation of the stimulus combination also depends on the synthesis of new proteins and RNA.

  1. The activation of visual memory for facial identity is task-dependent: evidence from human electrophysiology.

    Science.gov (United States)

    Zimmermann, Friederike G S; Eimer, Martin

    2014-05-01

    The question whether the recognition of individual faces is mandatory or task-dependent is still controversial. We employed the N250r component of the event-related potential as a marker of the activation of representations of facial identity in visual memory, in order to find out whether identity-related information from faces is encoded and maintained even when facial identity is task-irrelevant. Pairs of faces appeared in rapid succession, and the N250r was measured in response to repetitions of the same individual face, as compared to presentations of two different faces. In Experiment 1, an N250r was present in an identity matching task where identity information was relevant, but not when participants had to detect infrequent targets (inverted faces), and facial identity was task-irrelevant. This was the case not only for unfamiliar faces, but also for famous faces, suggesting that even famous face recognition is not as automatic as is often assumed. In Experiment 2, an N250r was triggered by repetitions of non-famous faces in a task where participants had to match the view of each face pair, and facial identity had to be ignored. This shows that when facial features have to be maintained in visual memory for a subsequent comparison, identity-related information is retained as well, even when it is irrelevant. Our results suggest that individual face recognition is neither fully mandatory nor completely task-dependent. Facial identity is encoded and maintained in tasks that involve visual memory for individual faces, regardless of the to-be-remembered feature. In tasks without this memory component, irrelevant visual identity information can be completely ignored. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    Directory of Open Access Journals (Sweden)

    Janna eMantua

    2015-06-01

    Full Text Available Individuals with a history of traumatic brain injury (TBI often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations. Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-hrs later, following an interval awake or with overnight sleep. Young adult participants (18-22 yrs were assigned to one of four experimental groups: TBI Sleep (n=14, TBI Wake (n=12, non-TBI Sleep (n=15, non-TBI Wake (n=15. Each TBI participant was >1 yr post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-hr intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation.

  3. Sleep-dependent consolidation patterns reveal insights into episodic memory structure.

    Science.gov (United States)

    Oyanedel, Carlos N; Sawangjit, Anuck; Born, Jan; Inostroza, Marion

    2018-05-18

    Episodic memory formation is considered a genuinely hippocampal function. Its study in rodents has relied on two different task paradigms, i.e. the so called "what-where-when" (WW-When) task and "what-where-which" (WW-Which) task. The WW-When task aims to assess the memory for an episode as an event bound into its context defined by spatial and distinct temporal information, the WW-Which task lacks the temporal component and introduces, instead, an "occasion setter" marking the broader contextual configuration in which the event occurred. Whether both tasks measure episodic memory in an equivalent manner in terms of recollection has been controversially discussed. Here, we compared in two groups of rats the consolidating effects of sleep on episodic-like memory between both task paradigms. Sampling and test phases were separated by a 90-min morning retention interval which did or did not allow for spontaneous sleep. Results show that sleep is crucial for the consolidation of the memory on both tasks. However, consolidating effects of sleep were stronger for the WW-Which than WW-When task. Comparing performance during the post-sleep test phase revealed that WW-When memory only gradually emerged during the 3-min test period whereas WW-Which memory was readily expressed already from the first minute onward. Separate analysis of the temporal and spatial components of WW-When performance showed that the delayed episodic memory on this task originated from the temporal component which also did not emerge until the third minute of the test phase, whereas the spatial component already showed up in the first minute. In conclusion, sleep differentially affects consolidation on the two episodic-like memory tasks, with the delayed expression of WW-When memory after sleep resulting from preferential coverage of temporal aspects by this task. Copyright © 2018. Published by Elsevier Inc.

  4. History-dependent excitability as a single-cell substrate of transient memory for information discrimination.

    Directory of Open Access Journals (Sweden)

    Fabiano Baroni

    Full Text Available Neurons react differently to incoming stimuli depending upon their previous history of stimulation. This property can be considered as a single-cell substrate for transient memory, or context-dependent information processing: depending upon the current context that the neuron "sees" through the subset of the network impinging on it in the immediate past, the same synaptic event can evoke a postsynaptic spike or just a subthreshold depolarization. We propose a formal definition of History-Dependent Excitability (HDE as a measure of the propensity to firing in any moment in time, linking the subthreshold history-dependent dynamics with spike generation. This definition allows the quantitative assessment of the intrinsic memory for different single-neuron dynamics and input statistics. We illustrate the concept of HDE by considering two general dynamical mechanisms: the passive behavior of an Integrate and Fire (IF neuron, and the inductive behavior of a Generalized Integrate and Fire (GIF neuron with subthreshold damped oscillations. This framework allows us to characterize the sensitivity of different model neurons to the detailed temporal structure of incoming stimuli. While a neuron with intrinsic oscillations discriminates equally well between input trains with the same or different frequency, a passive neuron discriminates better between inputs with different frequencies. This suggests that passive neurons are better suited to rate-based computation, while neurons with subthreshold oscillations are advantageous in a temporal coding scheme. We also address the influence of intrinsic properties in single-cell processing as a function of input statistics, and show that intrinsic oscillations enhance discrimination sensitivity at high input rates. Finally, we discuss how the recognition of these cell-specific discrimination properties might further our understanding of neuronal network computations and their relationships to the distribution and

  5. Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics

    DEFF Research Database (Denmark)

    Wise, Robert; Calverley, Peter Ma; Dahl, Ronald

    2015-01-01

    BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety...... in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. AIMS: The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy...... the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. CONCLUSIONS: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy....

  6. Short-lived brain state after cued motor imagery in naive subjects

    NARCIS (Netherlands)

    Pfurtscheller, G.; Scherer, R.; Müller-Putz, G.R.; Lopes da Silva, F.H.

    2008-01-01

    Multi-channel electroencephalography recordings have shown that a visual cue, indicating right hand, left hand or foot motor imagery, can induce a short-lived brain state in the order of about 500 ms. In the present study, 10 able-bodied subjects without any motor imagery experience (naive subjects)

  7. Arc/Arg3.1 mRNA global expression patterns elicited by memory recall in cerebral cortex differ for remote versus recent spatial memories

    Directory of Open Access Journals (Sweden)

    Pavel A Gusev

    2010-05-01

    Full Text Available The neocortex plays a critical role in the gradual formation and storage of remote declarative memories. Because the circuitry mechanisms of systems-level consolidation are not well understood, the precise cortical sites for memory storage and the nature of enduring memory correlates (mnemonic plasticity are largely unknown. Detailed maps of neuronal activity underlying recent and remote memory recall highlight brain regions that participate in systems consolidation and constitute putative storage sites, and thus may facilitate detection of mnemonic plasticity. To localize cortical regions involved in the recall of a spatial memory task, we trained rats in a water maze and then mapped mRNA expression patterns of a neuronal activity marker Arc/Arg3.1 (Arc upon recall of recent (24 hours after training or remote (one month after training memories and compared them with swimming and naive controls. Arc gene expression was significantly more robust 24 hours after training compared to one month after training. Arc expression diminished in the parietal, cingulate and visual areas, but select segments in the prefrontal, retrosplenial, somatosensory and motor cortical showed similar robust increases in the Arc expression. When Arc expression was compared across select segments of sensory, motor and associative regions within recent and remote memory groups, the overall magnitude and cortical laminar patterns of task-specific Arc expression were similar (stereotypical. Arc mRNA fractions expressed in the upper cortical layers (2/3, 4 increased after both recent and remote recall, while layer 6 fractions decreased only after the recent recall. The data suggest that robust recall of remote memory requires an overall smaller increase in neuronal activity within fewer cortical segments. This activity trend highlights the difficulty in detecting the storage sites and plasticity underlying remote memory. Application of the Arc maps may ameliorate this

  8. Early events governing memory CD8+ T-cell differentiation.

    Science.gov (United States)

    Obar, Joshua J; Lefrançois, Leo

    2010-08-01

    Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

  9. Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

    Science.gov (United States)

    Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

    2017-01-01

    In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The effects of cue distinctiveness on odor-based context-dependent memory.

    Science.gov (United States)

    Herz, R S

    1997-05-01

    The distinctiveness of an ambient odor was examined in relation to its success as a cue in context-dependent memory. Distinctiveness was examined in terms of both cue novelty and contextual appropriateness. Two experiments were conducted in which three different ambient odors that varied in familiarity and contextual appropriateness were manipulated at an incidental word learning encoding session and at a free recall retrieval session 48 h later. Experiment 1 revealed that when a novel ambient odor (osmanthus) was the available context cue, word recall was better than in any other condition. Further, among familiar odor cues, recall was better with a contextually inappropriate odor (peppermint) than with a contextually appropriate odor (clean fresh pine). Experiment 2 confirmed that superior word recall with osmanthus and peppermint depended on the odor cue's being available at both encoding and retrieval, and that the relation of an odor to the situational context is a key factor for predicting its effectiveness as a retrieval cue.

  11. Dose-Dependent Effect of Curcumin on Learning and Memory Deficit in Kainate-Epileptic Rats

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari

    2014-09-01

    Full Text Available Background & objectives : Epileptic seizures accompany disturbances in learning, memory, and cognitive skills. With regard to antiepileptic potential of curcumin and its beneficial effect on memory, the effect of its administration on learning and memory in kainate-epileptic rats was investigated.   Methods: Forty male rats were divided into sham, positive control ( valproate-treated epileptic, epileptic, and two curcumin-treated epileptic groups. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 4 μg of kainate per rat. Rats received intraperitoneal injection of curcumin (50 and 100 mg/kg daily for 1 week before surgery. For evaluation of learning and memory, initial (IL and step-through latencies (STL were determined using passive avoidance test and alternation behavior percentage was obtained according to Y maze test.   Results: Regarding IL, there was no significant difference between the groups. In contrast, STL significantly decreased in curcumin-50-treated epileptic group (p<0.05 (a change from 263.1 to 184.5 s. However, this parameter significantly increased in curcumin-100-treated epileptic group as compared to epileptic group (p<0.01 (a change from 263.1 to 220.3 s. In addition, STL was also significantly higher in valproic acid-treated epileptic group versus epileptic group (p<0.05 (a change from 145.7 to 210.3 s. Alternation percentage was also significantly higher in curcumin-50- and curcumin-100-treated epileptic groups relative to epileptic group (p<0.05 (a change from 60.5 to 77.6 and 80.3%.   Conclusion: Curcumin could dose-dependently enhance the consolidation and recall in epileptic animals and could improve spatial memory in such animals.

  12. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.

    Science.gov (United States)

    Weber, Jeffrey S; Kudchadkar, Ragini Reiney; Yu, Bin; Gallenstein, Donna; Horak, Christine E; Inzunza, H David; Zhao, Xiuhua; Martinez, Alberto J; Wang, Wenshi; Gibney, Geoffrey; Kroeger, Jodi; Eysmans, Cabell; Sarnaik, Amod A; Chen, Y Ann

    2013-12-01

    Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma. In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab. In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.

  13. The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.

    Science.gov (United States)

    Pitsikas, Nikolaos; Gravanis, Achille

    2017-04-01

    Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Short-term memory of motor network performance via activity-dependent potentiation of Na+/K+ pump function.

    Science.gov (United States)

    Zhang, Hong-Yan; Sillar, Keith T

    2012-03-20

    Brain networks memorize previous performance to adjust their output in light of past experience. These activity-dependent modifications generally result from changes in synaptic strengths or ionic conductances, and ion pumps have only rarely been demonstrated to play a dynamic role. Locomotor behavior is produced by central pattern generator (CPG) networks and modified by sensory and descending signals to allow for changes in movement frequency, intensity, and duration, but whether or how the CPG networks recall recent activity is largely unknown. In Xenopus frog tadpoles, swim bout duration correlates linearly with interswim interval, suggesting that the locomotor network retains a short-term memory of previous output. We discovered an ultraslow, minute-long afterhyperpolarization (usAHP) in network neurons following locomotor episodes. The usAHP is mediated by an activity- and sodium spike-dependent enhancement of electrogenic Na(+)/K(+) pump function. By integrating spike frequency over time and linking the membrane potential of spinal neurons to network performance, the usAHP plays a dynamic role in short-term motor memory. Because Na(+)/K(+) pumps are ubiquitously expressed in neurons of all animals and because sodium spikes inevitably accompany network activity, the usAHP may represent a phylogenetically conserved but largely overlooked mechanism for short-term memory of neural network function. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Encoding instructions and stimulus presentation in local environmental context-dependent memory studies.

    Science.gov (United States)

    Markopoulos, G; Rutherford, A; Cairns, C; Green, J

    2010-08-01

    Murnane and Phelps (1993) recommend word pair presentations in local environmental context (EC) studies to prevent associations being formed between successively presented items and their ECs and a consequent reduction in the EC effect. Two experiments were conducted to assess the veracity of this assumption. In Experiment 1, participants memorised single words or word pairs, or categorised them as natural or man made. Their free recall protocols were examined to assess any associations established between successively presented items. Fewest associations were observed when the item-specific encoding task (i.e., natural or man made categorisation of word referents) was applied to single words. These findings were examined further in Experiment 2, where the influence of encoding instructions and stimulus presentation on local EC dependent recognition memory was examined. Consistent with recognition dual-process signal detection model predictions and findings (e.g., Macken, 2002; Parks & Yonelinas, 2008), recollection sensitivity, but not familiarity sensitivity, was found to be local EC dependent. However, local EC dependent recognition was observed only after item-specific encoding instructions, irrespective of stimulus presentation. These findings and the existing literature suggest that the use of single word presentations and item-specific encoding enhances local EC dependent recognition.

  16. Accuracy Evaluation of C4.5 and Naive Bayes Classifiers Using Attribute Ranking Method

    Directory of Open Access Journals (Sweden)

    S. Sivakumari

    2009-03-01

    Full Text Available This paper intends to classify the Ljubljana Breast Cancer dataset using C4.5 Decision Tree and Nai?ve Bayes classifiers. In this work, classification is carriedout using two methods. In the first method, dataset is analysed using all the attributes in the dataset. In the second method, attributes are ranked using information gain ranking technique and only the high ranked attributes are used to build the classification model. We are evaluating the results of C4.5 Decision Tree and Nai?ve Bayes classifiers in terms of classifier accuracy for various folds of cross validation. Our results show that both the classifiers achieve good accuracy on the dataset.

  17. Robust Biometric Score Fusion by Naive Likelihood Ratio via Receiver Operating Characteristics

    NARCIS (Netherlands)

    Tao, Q.; Veldhuis, Raymond N.J.

    This paper presents a novel method of fusing multiple biometrics on the matching score level. We estimate the likelihood ratios of the fused biometric scores, via individual receiver operating characteristics (ROC) which construct the Naive Bayes classifier. Using a limited number of operation

  18. Short-term memory and strategy use in children with insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Wolters, C A; Yu, S L; Hagen, J W; Kail, R

    1996-12-01

    The present study was designed to examine recall and rehearsal in short-term memory among children with insulin-dependent diabetes mellitus (IDDM). Children with onset of IDDM before age 5 years, children with onset after 5 years, and children without IDDM were administered a measure of short-term memory that provides information about rehearsal as well as level of recall. Children with later onset of diabetes and children without IDDM were expected to recall more words and use more effective rehearsal strategies than children with early onset of diabetes. Results indicate that children diagnosed with IDDM early in life used similar rehearsal strategies but recalled fewer words than children with later onset of diabetes and children without IDDM. In addition, results provide evidence that children who are in poor control of their diabetes did not use strategies designed to increase recall as often, or as well as, children in better control of their diabetes.

  19. Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment

    DEFF Research Database (Denmark)

    Sjo, Christina Power; Stenstrøm, Anne Dorte; Bojesen, Anders Bo

    2017-01-01

    if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG......), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. RESULTS: The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p 

  20. Emotion strengthens high-priority memory traces but weakens low-priority memory traces.

    Science.gov (United States)

    Sakaki, Michiko; Fryer, Kellie; Mather, Mara

    2014-02-01

    When people encounter emotional events, their memory for those events is typically enhanced. But it has been unclear how emotionally arousing events influence memory for preceding information. Does emotional arousal induce retrograde amnesia or retrograde enhancement? The current study revealed that this depends on the top-down goal relevance of the preceding information. Across three studies, we found that emotional arousal induced by one image facilitated memory for the preceding neutral item when people prioritized that neutral item. In contrast, an emotionally arousing image impaired memory for the preceding neutral item when people did not prioritize that neutral item. Emotional arousal elicited by both negative and positive pictures showed this pattern of enhancing or impairing memory for the preceding stimulus depending on its priority. These results indicate that emotional arousal amplifies the effects of top-down priority in memory formation.

  1. Verbal Short-Term Memory Span in Children: Long-Term Modality Dependent Effects of Intrauterine Growth Restriction

    Science.gov (United States)

    Geva, R.; Eshel, R.; Leitner, Y.; Fattal-Valevski, A.; Harel, S.

    2008-01-01

    Background: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. Methods: This long-term, prospective design study…

  2. The Effect of Naive Ideas on Students' Reasoning about Electricity and Magnetism

    Science.gov (United States)

    Leppavirta, Johanna

    2012-01-01

    Traditional multiple-choice concept inventories measure students' critical conceptual understanding and are designed to reveal students' naive or alternate ideas. The overall scores, however, give little information about the state of students' knowledge and the consistency of reasoning. This study investigates whether students have consistent…

  3. Modeling spatial-temporal operations with context-dependent associative memories.

    Science.gov (United States)

    Mizraji, Eduardo; Lin, Juan

    2015-10-01

    We organize our behavior and store structured information with many procedures that require the coding of spatial and temporal order in specific neural modules. In the simplest cases, spatial and temporal relations are condensed in prepositions like "below" and "above", "behind" and "in front of", or "before" and "after", etc. Neural operators lie beneath these words, sharing some similarities with logical gates that compute spatial and temporal asymmetric relations. We show how these operators can be modeled by means of neural matrix memories acting on Kronecker tensor products of vectors. The complexity of these memories is further enhanced by their ability to store episodes unfolding in space and time. How does the brain scale up from the raw plasticity of contingent episodic memories to the apparent stable connectivity of large neural networks? We clarify this transition by analyzing a model that flexibly codes episodic spatial and temporal structures into contextual markers capable of linking different memory modules.

  4. The Effect of Reversible Abolition of Basolateral Amygdala on Hippocampal Dependent Spatial Memory Processes in Mice

    Directory of Open Access Journals (Sweden)

    A Rashidy-Pour

    2004-04-01

    Full Text Available Introduction: Many evidences have suggested that the Basolateral Amygdala (BLA are probably involved in emotional learning and modulation of spatial memory processes. The aim of this present study was assessment of the effect of reversible abolition of BLA on spatial memory processes in a place avoidance learning model in a stable environment. Methods and Materials: Long-Evans strain rats (280-320 gr. were selected and cannulae aimed at the BLA were surgically implanted bilaterally. The mice were trained to avoid a 60° segment of the arena by punishing with a mild foot shock upon entering the area. The punished sector was defined by room cues during the place avoidance training, which occurred in a single 30-min session and the avoidance memory was assessed during a 30-min extinction trial after 24 hours. The time of the first entry and the number of entrances into the punished sector during extinction were used to measure the place avoidance memory. Bilateral injections of Tetrodotoxin (5ng/0.6ml per side were used to inactivate the BLA 60 min before acquisition, immediately, 60 and 120 min after training, or 60 min before the retrieval test. Control mice were injected saline at the same time. Results : The results indicated that acquisition, consolidation (immediately, 60 min after training and retrieval of spatial memory in stable arena were impaired (p0.05. Conclusion: We conclude that the Basolateral Amygdala (BLA modulate spatial memory processes in place avoidance learning model in stable arena and this effect in regard to consolidation is time dependent.

  5. Role of adult neurogenesis in hippocampal-cortical memory consolidation

    Science.gov (United States)

    2014-01-01

    Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

  6. Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons.

    Science.gov (United States)

    Shobe, Justin L; Zhao, Yali; Stough, Shara; Ye, Xiaojing; Hsuan, Vickie; Martin, Kelsey C; Carew, Thomas J

    2009-01-15

    An activity-dependent form of intermediate memory (AD-ITM) for sensitization is induced in Aplysia by a single tail shock that gives rise to plastic changes (AD-ITF) in tail sensory neurons (SNs) via the interaction of action potential firing in the SN coupled with the release of serotonin in the CNS. Activity-dependent long-term facilitation (AD-LTF, lasting >24hr) requires protein synthesis dependent persistent mitogen-activated protein kinase (MAPK) activation and translocation to the SN nucleus. We now show that the induction of the earlier temporal phase (AD-ITM and AD-ITF), which is translation and transcription independent, requires the activation of a compartmentally distinct novel signaling cascade that links second messengers, MAPK and PKC into a unified pathway within tail SNs. Since both AD-ITM and AD-LTM require MAPK activity, these collective findings suggest that presynaptic SNs route the flow of molecular information to distinct subcellular compartments during the induction of activity-dependent long-lasting memories.

  7. Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress.

    Science.gov (United States)

    Campbell, Adam M; Park, Collin R; Zoladz, Phillip R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

    2008-02-01

    Extensive research has shown that the antidepressant tianeptine blocks the adverse effects of chronic stress on hippocampal functioning. The current series of experiments extended this area of investigation by examining the influence of tianeptine on acute stress-induced impairments of spatial (hippocampus-dependent) memory. Tianeptine (10 mg/kg, ip) administered to adult male rats before, but not after, water maze training blocked the amnestic effects of predator stress (occurring between training and retrieval) on memory. The protective effects of tianeptine on memory occurred in rats which had extensive pre-stress training, as well as in rats which had only a single day of training. Tianeptine blocked stress effects on memory without altering the stress-induced increase in corticosterone levels. Propranolol, a beta-adrenergic receptor antagonist (5 and 10 mg/kg, ip), in contrast, did not block stress-induced amnesia. These findings indicate that treatment with tianeptine, unlike propanolol, provides an effective means with which to block the adverse effects of stress on cognitive functions of the hippocampus.

  8. Penerapan Data Mining Algoritma Naives Bayes dan PART Untuk Mengetahui Minat Baca Mahasiswa di Perpustakaan STMIK AMIKOM Purwokerto

    Directory of Open Access Journals (Sweden)

    Mohammad Imron

    2017-08-01

    Full Text Available Perpustakaan STMIK AMIKOM Purwokerto didirikan dengan tujuan untuk membantu serta memenuhi kebutuhan sivitas akademik yang ada di Perguruan Tinggi, koleksi buku yang ada sekitar 12,518, dengan judul 6,375 eksemplar. Penelitian ini bertujuan untuk mengetahui minat baca mahasiswa dengan membandingkan tingkat akurasi pada data mining dengan menggunakan algoritma naive bayes dan PART berdasarkan data peminjaman. Pengambilan data dari bulan Januari 2016 sampai bulan Maret 2017 dengan total data 4022. Hasil pengujian yang telah dilakukan terhadap kedua algoritma yaitu algoritma Naive Bayes dan Algoritma PART, maka dapat disimpulkan dari evaluasi dengan confusion matrix didapat hasil nilai akurasi masing-masing algoritma, nilai akurasi dari algoritma naive bayes sebesar 97,01% dan nilai akurasi dari algoritma PART sebesar 97,19%, sehingga algoritma yang terbaik dari pengujian tersebut untuk mengetahui minat baca mahasiswa di Perpustakaan STMIK AMIKOM Purwokerto adalah algoritma PART.

  9. Frequency-dependent brain regional homogeneity alterations in patients with mild cognitive impairment during working memory state relative to resting state

    Directory of Open Access Journals (Sweden)

    Pengyun eWang

    2016-03-01

    Full Text Available Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI. However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control subjects. Therefore, using the index of regional homogeneity (ReHo, we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex in the slow-3 band (0.073–0.198 Hz, and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex, the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01–0.027 Hz. Furthermore, in normal controls, the value of ReHo in clusters belonging to the default mode network decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients.This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states.

  10. The time course of working memory effects on visual attention differs depending on memory type

    NARCIS (Netherlands)

    Dombrowe, I.; Olivers, C.N.L.; Donk, M.

    2010-01-01

    Previous work has generated inconsistent results with regard to what extent working memory (WM) content guides visual attention. Some studies found effects of easy to verbalize stimuli, whereas others only found an influence of visual memory content. To resolve this, we compared the time courses of

  11. Bisphenol A impairs the memory function and glutamatergic homeostasis in a sex-dependent manner in mice: Beneficial effects of diphenyl diselenide.

    Science.gov (United States)

    Jardim, Natália S; Sartori, Glaúbia; Sari, Marcel H M; Müller, Sabrina G; Nogueira, Cristina W

    2017-08-15

    Bisphenol A (BPA) is a compound integrated in commodities, which consequently increases the human exposure to this toxicant. The deleterious effects of BPA exposure during periods of brain development have been documented mainly concerning the impairment in memory functions. Diphenyl diselenide (PhSe) 2 , an organoselenium compound, shows protective/restorative effects against memory deficits in experimental models. Thus, this study investigated the effects of (PhSe) 2 on the memory impairments induced by BPA exposure to male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old male and female Swiss mice received BPA (5mg/kg), intragastrically, from 21st to 60th postnatal day. After, the animals were intragastrically treated with (PhSe) 2 (1mg/kg) during seven days. The mice performed the behavioral memory tests and the [ 3 H] glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the passive avoidance memory in male mice. Besides, BPA caused a decrease in the [ 3 H] glutamate uptake and NMDA receptor subunit levels in the cortical and hippocampal regions depending on the sex. Treatment with (PhSe) 2 reversed in a sex-independent manner the behavioral impairments and molecular alterations. In conclusion, BPA had a negative effect in different memory types as well as in the glutamatergic parameters in a sex-dependent manner and (PhSe) 2 treatment was effective against these alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  13. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  14. Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks.

    Directory of Open Access Journals (Sweden)

    Su-Hyun Kim

    Full Text Available Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice. Both contextual fear conditioning (CFC and object-location recognition tasks were impaired in recent (1 day memory test while passive avoidance task was impaired only in remote (≥ 20 days memory in KO mice. Results using adeno-associated virus (AAV-mediated Cav1.3 knock-down (KD or retrovirus-mediated KD in dorsal hippocampal DG area showed that the recent memory of CFC was impaired in both KD mice but the remote memory was impaired only in AAV KD mice, suggesting that Cav1.3 of mature neurons play important roles in both recent and remote CFC memory while Cav1.3 in newborn neurons is selectively involved in the recent CFC memory process. Meanwhile, AAV KD of Cav1.3 in ventral hippocampal area has no effect on the recent CFC memory. In conclusion, the results suggest that Cav1.3 in newborn neurons of dorsal hippocampus is involved in the survival of newborn neurons while mediating developments of dendritic and axonal processes of newborn cells and plays a role in the memory process differentially depending on the stage of maturation and the type of learning task.

  15. Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks.

    Science.gov (United States)

    Kim, Su-Hyun; Park, Ye-Ryoung; Lee, Boyoung; Choi, Byungil; Kim, Hyun; Kim, Chong-Hyun

    2017-01-01

    Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO) of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB) filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice. Both contextual fear conditioning (CFC) and object-location recognition tasks were impaired in recent (1 day) memory test while passive avoidance task was impaired only in remote (≥ 20 days) memory in KO mice. Results using adeno-associated virus (AAV)-mediated Cav1.3 knock-down (KD) or retrovirus-mediated KD in dorsal hippocampal DG area showed that the recent memory of CFC was impaired in both KD mice but the remote memory was impaired only in AAV KD mice, suggesting that Cav1.3 of mature neurons play important roles in both recent and remote CFC memory while Cav1.3 in newborn neurons is selectively involved in the recent CFC memory process. Meanwhile, AAV KD of Cav1.3 in ventral hippocampal area has no effect on the recent CFC memory. In conclusion, the results suggest that Cav1.3 in newborn neurons of dorsal hippocampus is involved in the survival of newborn neurons while mediating developments of dendritic and axonal processes of newborn cells and plays a role in the memory process differentially depending on the stage of maturation and the type of learning task.

  16. Statistical Estimation for CAPM with Long-Memory Dependence

    Directory of Open Access Journals (Sweden)

    Tomoyuki Amano

    2012-01-01

    Full Text Available We investigate the Capital Asser Pricing Model (CAPM with time dimension. By using time series analysis, we discuss the estimation of CAPM when market portfolio and the error process are long-memory process and correlated with each other. We give a sufficient condition for the return of assets in the CAPM to be short memory. In this setting, we propose a two-stage least squares estimator for the regression coefficient and derive the asymptotic distribution. Some numerical studies are given. They show an interesting feature of this model.

  17. Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

    Directory of Open Access Journals (Sweden)

    Zalina Zahari

    2018-06-01

    Full Text Available ABSTRACT Opioidergic system involves in regulation of sleep and wakefulness. It is possible, therefore, that genetic polymorphisms in OPRM1 influence sleep quality. This study investigated the association of OPRM1 polymorphisms with subjective sleep quality among opioid-naive individuals. This cross-sectional observational study involved 161 opioid-naive males (mean age = 27.74 years; range: 18−63 years. Subjective sleep quality was assessed with the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI. DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR-genotyping for two OPRM1 polymorphisms (118A>G and IVS2+691G>C. Subjects with combined 118A and IVS2+691G alleles (AC haplotype had significantly lower PSQI scores [mean (SD = 4.29 (1.76] compared to those without the haplotype [4.99 (2.50] (p = 0.004. On the other hand, subjects with combined heterozygous genotype (GC/AG diplotype had significantly higher PSQI scores compared to those without the diplotype [6.04 (2.48 vs 4.54 (2.22, p = 0.004]. In opioid-naive individuals, AC haplotype and GC/AG diplotype for the 118A>G and IVS2+691G>C polymorphisms of OPRM1 are associated with better and poorer sleep quality, respectively.

  18. Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells*

    Science.gov (United States)

    Ali, Ramadan A.; Camick, Christina; Wiles, Katherine; Walseth, Timothy F.; Slama, James T.; Bhattacharya, Sumit; Giovannucci, David R.; Wall, Katherine A.

    2016-01-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+ mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. PMID:26728458

  19. Autobiographical Memory Deficits in Alcohol-Dependent Patients with Short- and Long-Term Abstinence.

    Science.gov (United States)

    Nandrino, Jean-Louis; El Haj, Mohamad; Torre, Julie; Naye, Delphine; Douchet, Helyette; Danel, Thierry; Cottençin, Oliver

    2016-04-01

    Autobiographical memory (AM) enables the storage and retrieval of life experiences that allow individuals to build their sense of identity. Several AM impairments have been described in patients with alcohol abuse disorders without assessing whether such deficits can be recovered. This cross-sectional study aimed to identify whether the semantic (SAM) and episodic (EAM) dimensions of AM are affected in individuals with alcohol dependence after short-term abstinence (STA) or long-term abstinence (LTA). A second aim of this study was to examine the factors that could disrupt the efficiency of semantic and episodic AM (the impact of depression severity, cognitive functions, recent or early traumatic events, and drinking history variables). After clinical and cognitive evaluations (alcohol consumption, depression, anxiety, IQ, memory performance), AM was assessed with the Autobiographical Memory Interview in patients with recent (between 4 and 6 weeks) and longer (at least 6 months) abstinence. Participants were asked to retrieve the number and nature of traumatic or painful life experiences in recent or early life periods (using the Childhood Traumatic Events Scale). The 2 abstinent groups had lower global EAM and SAM scores than the control group. These scores were comparable for both abstinent groups. For childhood events, no significant differences were observed in SAM for both groups compared with control participants. For early adulthood and recent events, both STA and LTA groups had lower scores on both SAM and EAM. Moreover, there was a negative correlation between the length of substance consumption and SAM scores. This study highlighted a specific AM disorder in both episodic and semantic dimensions. These deficits remained after 6 months of abstinence. This AM impairment may be explained by compromised encoding and consolidation of memories during bouts of drinking. Copyright © 2016 by the Research Society on Alcoholism.

  20. The relation between T-cell expression of LFA-1 and immunological memory

    DEFF Research Database (Denmark)

    Hviid, L; Odum, N; Theander, T G

    1993-01-01

    Antibodies against isotypes of the leucocyte common antigen (LCA, CD45) can be used to identify largely reciprocal subsets of human peripheral T cells, characterized by differential ability to respond to recall antigen in vitro. The transition from naive, unprimed T cells to memory cells capable...... of responding to recall stimulating has been associated with a switch in surface expression of CD45 from the CD45RA isotype to CD45RO. It has been proposed that this transition is accompanied by the coordinated up-regulation of a number of cell-surface molecules involved in cellular adhesion and/or activation......, including the leucocyte function-associated antigens (LFA). In the present study we have examined the expression of LFA-1 on subsets of human peripheral T cells, and related it to the expression of markers of cellular activation and CD45 isotypes, and thus to immunological memory. Our results suggest...

  1. The Effect of Opium Dependency of Parent (s) on Offspring's Spatial Learning & Memory in Adult Male Rats.

    Science.gov (United States)

    Saberi Moghadam, Arezoo; Sepehri, Gholamreza; Sheibani, Vahid; Haghpanah, Tahereh; Divsalar, Kouros; Hajzadeh, Mousa-Al-Reza; Afarineshkhaki, Mohammadreza

    2013-05-01

    As far as we know, there has been no report regarding the effects of opium addiction or dependency of both parents on the learning and memory process in offspring. The aim of this study was to examine the learning and memory changes of adult male offspring whose mothers, fathers and/or both parents had dependency to opium before and during pregnancy. Materials and Methods : All experiments were carried out on Wistar rats. Opium dependency was induced by daily injections of opium (10 mg/kg/SC, bid/10 d) before mating. The presence of a vaginal plug was designated as gestation day. Treatment with opium continued through breeding and gestation until parturition. Spatial memory was tested in male offspring of control, saline and prenatal opium treated groups by a training trial and the probe test in the Morris water maze. Swimming escape latency in the maze and the ability to find the platform in the training trial were recorded. The time spent in the trigger zone and number of times the rats crossed the platform during the probe phase and swimming speed were measured. The data revealed increased escape latency and a greater distance traveled to find the hidden platform in the offspring's whose mother, father and /or both parents were exposed to opium. Crossings to target quadrant at probe trials was significantly reduced in all of the prenatal opium exposed offsprings. The swimming speed showed a significant increase in father and parent's opium exposed offspring. Prenatal opium exposure of either parent may cause deficits in spatial learning, but the precise mechanism(s) remain largely unknown.

  2. Magnetic resonance imaging-guided biopsies may improve diagnosis in biopsy-naive men with suspicion of prostate cancer

    DEFF Research Database (Denmark)

    Winther, Mads Dochedahl; Balslev, Ingegerd; Boesen, Lars

    2017-01-01

    INTRODUCTION: The purpose of this pilot study was to investigate whether a short prostate biparametric magnetic resonance imaging (bp-MRI) protocol provides a valuable diagnostic addition for biopsy guidance in biopsy-naive men with a suspicion of prostate cancer (PCa). METHODS: A total of 62...... biopsy-naive patients referred to a systematic transrectal ultrasound biopsy (TRUS-bx) due to suspicion of PCa were prospectively enrolled. Bp-MRI was performed before biopsy. All lesions were scored according to the modified Prostate Imaging Reporting and Data System (PI-RADS) version 2. All patients...

  3. Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis.

    Science.gov (United States)

    Mastrodonato, Alessia; Barbati, Saviana Antonella; Leone, Lucia; Colussi, Claudia; Gironi, Katia; Rinaudo, Marco; Piacentini, Roberto; Denny, Christine A; Grassi, Claudio

    2018-01-10

    Exposure to extremely low-frequency electromagnetic fields (ELFEF) influences the expression of key target genes controlling adult neurogenesis and modulates hippocampus-dependent memory. Here, we assayed whether ELFEF stimulation affects olfactory memory by modulating neurogenesis in the subventricular zone (SVZ) of the lateral ventricle, and investigated the underlying molecular mechanisms. We found that 30 days after the completion of an ELFEF stimulation protocol (1 mT; 50 Hz; 3.5 h/day for 12 days), mice showed enhanced olfactory memory and increased SVZ neurogenesis. These effects were associated with upregulated expression of mRNAs encoding for key regulators of adult neurogenesis and were mainly dependent on the activation of the Wnt pathway. Indeed, ELFEF stimulation increased Wnt3 mRNA expression and nuclear localization of its downstream target β-catenin. Conversely, inhibition of Wnt3 by Dkk-1 prevented ELFEF-induced upregulation of neurogenic genes and abolished ELFEF's effects on olfactory memory. Collectively, our findings suggest that ELFEF stimulation increases olfactory memory via enhanced Wnt/β-catenin signaling in the SVZ and point to ELFEF as a promising tool for enhancing SVZ neurogenesis and olfactory function.

  4. The effect of chronic corticosterone on fear learning and memory depends on dose and the testing protocol.

    Science.gov (United States)

    Marks, W N; Fenton, E Y; Guskjolen, A J; Kalynchuk, L E

    2015-03-19

    Chronic exposure to the stress hormone corticosterone (CORT) is known to alter plasticity within hippocampal and amygdalar circuits that mediate fear learning and memory. The purpose of this experiment was to clarify the effects of chronic CORT on Pavlovian fear conditioning, which is dependent on intact hippocampal and amygdalar activity. In particular, we assessed whether the effect of chronic CORT on fear learning and memory is influenced by two factors-the dose of CORT and the order in which rats are tested for freezing to context versus tone cues. Male Long-Evans rats received low-dose CORT (5mg/kg), high-dose CORT (40mg/kg), or vehicle injections once daily for 21days. On day 22, the rats were trained in a fear-conditioning paradigm. On days 23 and 24, the rats were tested for the retrieval of fear memories to context and tone cues in a counterbalanced way-half the rats received context testing on day 23 and then tone testing on day 24 and half the rats received tone testing on day 23 followed by context testing on day 24. Our results revealed dose-dependent effects of CORT on memory retrieval: Rats injected with high-dose CORT froze significantly more than control rats to both context and tone cues regardless of what testing day these cues were presented. However, rats injected with low-dose CORT froze significantly more than control rats to tone cues only. We also found an order effect in that the effects of CORT on freezing were greater on the second day of testing, regardless of whether that testing was to context or tones cues. This order effect may be due to a lack of extinction in the CORT rats. Overall, these results suggest a relationship between stress intensity and testing conditions that should be taken into account when assessing the effect of stress on fear memories. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Context-dependent enhancement of declarative memory performance following acute psychosocial stress.

    Science.gov (United States)

    Smeets, T; Giesbrecht, T; Jelicic, M; Merckelbach, H

    2007-09-01

    Studies on how acute stress affects learning and memory have yielded inconsistent findings, with some studies reporting enhancing effects while others report impairing effects. Recently, Joëls et al. [Joëls, M., Pu, Z., Wiegert, O., Oitzl, M.S., Krugers, H.J., 2006. Learning under stress: how does it work? Trends in Cognitive Sciences, 10, 152-158] argued that stress will enhance memory only when the memory acquisition phase and stressor share the same spatiotemporal context (i.e., context-congruency). The current study tested this hypothesis by looking at whether context-congruent stress enhances declarative memory performance. Undergraduates were assigned to a personality stress group (n=16), a memory stress group (n=18), or a no-stress control group (n=18). While being exposed to the acute stressor or a control task, participants encoded personality- and memory-related words and were tested for free recall 24h later. Relative to controls, stress significantly enhanced recall of context-congruent words, but only for personality words. This suggests that acute stress may strengthen the consolidation of memory material when the stressor matches the to-be-remembered information in place and time.

  6. Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

    Science.gov (United States)

    Barsegyan, Areg; Mackenzie, Scott M.; Kurose, Brian D.; McGaugh, James L.; Roozendaal, Benno

    2010-01-01

    It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC. PMID:20810923

  7. Reversal of cycloheximide-induced memory disruption by AIT-082 (Neotrofin) is modulated by, but not dependent on, adrenal hormones.

    Science.gov (United States)

    Yan, Rongzi; Nguyen, Quang; Gonzaga, James; Johnson, Mai; Ritzmann, Ronald F; Taylor, Eve M

    2003-04-01

    AIT-082 (Neotrofin), a hypoxanthine derivative, has been shown to improve memory in both animals and humans. In animals, adrenal hormones modulate the efficacy of many memory-enhancing compounds, including piracetam and tacrine (Cognex). To investigate the role of adrenal hormones in the memory-enhancing action of AIT-082. Plasma levels of adrenal hormones (corticosterone and aldosterone) in mice were significantly reduced by surgical or chemical (aminoglutethimide) adrenalectomy or significantly elevated by oral administration of corticosterone. The effects of these hormone level manipulations on the memory-enhancing activity of AIT-082 and piracetam were evaluated using a cycloheximide-induced amnesia/passive avoidance model. As previously reported by others, the memory enhancing action of piracetam was abolished by adrenalectomy. In contrast, the memory enhancement by 60 mg/kg AIT-082 (IP) was unaffected. However, a sub-threshold dose of AIT-082 (0.1 mg/kg, IP) that did not improve memory in control animals did improve memory in adrenalectomized animals. These data suggested that, similar to piracetam and tacrine, the memory enhancing action of AIT-082 might be inhibited by high levels of adrenal hormones. As expected, corticosterone (30 and 100 mg/kg) inhibited the action of piracetam, however no dose up to 100 mg/kg corticosterone inhibited the activity of AIT-082. These data suggest that while AIT-082 function is not dependent on adrenal hormones, it is modulated by them. That memory enhancement by AIT-082 was not inhibited by high plasma corticosterone levels may have positive implications for its clinical utility, given that many Alzheimer's disease patients have elevated plasma cortisol levels.

  8. Flavor Memory

    NARCIS (Netherlands)

    Mojet, Jos; Köster, Ep

    2016-01-01

    Odor, taste, texture, temperature, and pain all contribute to the perception and memory of food flavor. Flavor memory is also strongly linked to the situational aspects of previous encounters with the flavor, but does not depend on the precise recollection of its sensory features as in vision and

  9. Stateless Malware Packet Detection by Incorporating Naive Bayes with Known Malware Signatures

    Directory of Open Access Journals (Sweden)

    Ismahani Ismail

    2014-01-01

    Full Text Available Malware detection done at the network infrastructure level is still an open research problem ,considering the evolution of malwares and high detection accuracy needed to detect these threats. Content based classification techniques have been proven capable of detecting malware without matching for malware signatures. However, the performance of the classification techniques depends on observed training samples. In this paper, a new detection method that incorporates Snort malware signatures into Naive Bayes model training is proposed. Through experimental work, we prove that the proposed work results in low features search space for effective detection at the packet level. This paper also demonstrates the viability of detecting malware at the stateless level (using packets as well as at the stateful level (using TCP byte stream. The result shows that it is feasible to detect malware at the stateless level with similar accuracy to the stateful level, thus requiring minimal resource for implementation on middleboxes. Stateless detection can give a better protection to end users by detecting malware on middleboxes without having to reconstruct stateful sessions and before malwares reach the end users.

  10. IFN-Gamma-Dependent and Independent Mechanisms of CD4+ Memory T Cell-Mediated Protection from Listeria Infection

    Directory of Open Access Journals (Sweden)

    Stephanie M. Meek

    2018-02-01

    Full Text Available While CD8+ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4+ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV, followed by a heterologous rechallenge with Listeria monocytogenes recombinantly expressing the MHC Class II-restricted LCMV epitope, GP61–80 (Lm-gp61. We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4+ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4+ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4+ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4+ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4+ memory T cells from heterologous Listeria challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role.

  11. Dreams are made of memories, but maybe not for memory.

    Science.gov (United States)

    Blagrove, Mark; Ruby, Perrine; Eichenlaub, Jean-Baptiste

    2013-12-01

    Llewellyn's claim that rapid eye movement (REM) dream imagery may be related to the processes involved in memory consolidation during sleep is plausible. However, whereas there is voluntary and deliberate intention behind the construction of images in the ancient art of memory (AAOM) method, there is a lack of intentionality in producing dream images. The memory for dreams is also fragile, and dependent on encoding once awake.

  12. Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

    Science.gov (United States)

    Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

    2013-08-01

    Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

  13. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Skimminge, Arnold; Rasmussen, Hans

    2011-01-01

    . Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement of negative symptoms. Progressive regional volume loss in quetiapine-treated, first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying...... scarcely been investigated. Here we investigated structural brain changes in antipsychotic-naive, first-episode schizophrenia patients after 6 months treatment with the SGA, quetiapine. We have recently reported on baseline volume reductions in the caudate nucleus and hippocampus. Baseline and follow-up T1......-weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations...

  14. Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

    Science.gov (United States)

    Plihal, W; Born, J

    1999-09-09

    Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

  15. Personality matters: individual variation in reactions of naive bird predators to aposematic prey

    NARCIS (Netherlands)

    Exnerová, A.; Hotova Svadova, K.; Fucikova, E.; Drent, P.; Stys, P.

    2010-01-01

    Variation in reactions to aposematic prey is common among conspecific individuals of bird predators. It may result from different individual experience but it also exists among naive birds. This variation may possibly be explained by the effect of personality—a complex of correlated, heritable

  16. Using Unsupervised Learning to Improve the Naive Bayes Classifier for Wireless Sensor Networks

    NARCIS (Netherlands)

    Zwartjes, G.J.; Havinga, Paul J.M.; Smit, Gerardus Johannes Maria; Hurink, Johann L.

    2012-01-01

    Online processing is essential for many sensor network applications. Sensor nodes can sample far more data than what can practically be transmitted using state of the art sensor network radios. Online processing, however, is complicated due to limited resources of individual nodes. The naive Bayes

  17. Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.

    Science.gov (United States)

    Ali, Ramadan A; Camick, Christina; Wiles, Katherine; Walseth, Timothy F; Slama, James T; Bhattacharya, Sumit; Giovannucci, David R; Wall, Katherine A

    2016-02-26

    Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing second messenger discovered to date, has been implicated in Ca(2+) signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca(2+) signaling or the identity of the Ca(2+) stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca(2+) signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca(2+) signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca(2+) stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca(2+) signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca(2+) release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

    Science.gov (United States)

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2009-12-01

    The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (Pchronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

  19. Iron Loading Selectively Increases Hippocampal Levels of Ubiquitinated Proteins and Impairs Hippocampus-Dependent Memory.

    Science.gov (United States)

    Figueiredo, Luciana Silva; de Freitas, Betânia Souza; Garcia, Vanessa Athaíde; Dargél, Vinícius Ayub; Köbe, Luiza Machado; Kist, Luiza Wilges; Bogo, Maurício Reis; Schröder, Nadja

    2016-11-01

    Alterations of brain iron levels have been observed in a number of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in the adulthood. Protein degradation mediated by the ubiquitin-proteasome system (UPS) plays a central regulatory role in several cellular processes. Impairment of the UPS has been implicated in the pathogenesis of neurodegenerative disorders. Here, we examined the effects of iron exposure in the neonatal period (12th-14th day of postnatal life) on the expression of proteasome β-1, β-2, and β-5 subunits, and ubiquitinated proteins in brains of 15-day-old rats, to evaluate the immediate effect of the treatment, and in adulthood to assess long-lasting effects. Two different memory types, emotionally motivated conditioning and object recognition were assessed in adult animals. We found that iron administered in the neonatal period impairs both emotionally motivated and recognition memory. Polyubiquitinated protein levels were increased in the hippocampus, but not in the cortex, of adult animals treated with iron. Gene expression of subunits β1 and β5 was affected by age, being higher in the early stages of development in the hippocampus, accompanied by an age-related increase in polyubiquitinated protein levels in adults. In the cortex, gene expression of the three proteasome subunits was significantly higher in adulthood than in the neonatal period. These findings suggest that expression of proteasome subunits and activity are age-dependently regulated. Iron exposure in the neonatal period produces long-lasting harmful effects on the UPS functioning, which may be related with iron-induced memory impairment.

  20. Neuroprotective mechanism of Lycium barbarum polysaccharides against hippocampal-dependent spatial memory deficits in a rat model of obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Chun-Sing Lam

    Full Text Available Chronic intermittent hypoxia (CIH is a hallmark of obstructive sleep apnea (OSA, which induces hippocampal injuries mediated by oxidative stress. This study aims to examine the neuroprotective mechanism of Lycium barbarum polysaccharides (LBP against CIH-induced spatial memory deficits. Adult Sprague-Dawley rats were exposed to hypoxic treatment resembling a severe OSA condition for a week. The animals were orally fed with LBP solution (1 mg/kg daily 2 hours prior to hypoxia or in air for the control. The effect of LBP on the spatial memory and levels of oxidative stress, inflammation, endoplasmic reticulum (ER stress, apoptosis and neurogenesis in the hippocampus was examined. There was a significant deficit in the spatial memory and an elevated level of malondialdehyde with a decreased expression of antioxidant enzymes (SOD, GPx-1 in the hypoxic group when compared with the normoxic control. In addition, redox-sensitive nuclear factor kappa B (NFКB canonical pathway was activated with a translocation of NFКB members (p65, p50 and increased expression levels of NFКB-dependent inflammatory cytokines and mediator (TNFα, IL-1β, COX-2; also, a significantly elevated level of ER stress (GRP78/Bip, PERK, CHOP and autophagic flux in the hypoxic group, leading to neuronal apoptosis in hippocampal subfields (DG, CA1, CA3. Remarkably, LBP administration normalized the elevated level of oxidative stress, neuroinflammation, ER stress, autophagic flux and apoptosis induced by hypoxia. Moreover, LBP significantly mitigated both the caspase-dependent intrinsic (Bax, Bcl2, cytochrome C, cleaved caspase-3 and extrinsic (FADD, cleaved caspase-8, Bid signaling apoptotic cascades. Furthermore, LBP administration prevented the spatial memory deficit and enhanced the hippocampal neurogenesis induced by hypoxia. Our results suggest that LBP is neuroprotective against CIH-induced hippocampal-dependent spatial memory deficits by promoting hippocampal neurogenesis

  1. Stressors impair odor recognition memory via an olfactory bulb-dependent noradrenergic mechanism

    Directory of Open Access Journals (Sweden)

    Laura C Manella

    2013-12-01

    Full Text Available Non-associative habituation and odor recognition tasks have been widely used to probe questions social recognition, odor memory duration, and odor memory specificity. Among others, these paradigms have provided valuable insight into how neuromodulation, and specifically norepinephrine/noradrenaline (NE influences odor memory. In general, NE levels are modulated by arousal, stress, and behavioral state, and there is sparse evidence of a direct relationship between NE and odor memory in adult rodents. The present study uses simple mild psychological stressors (bright light and sound, to modulate NE levels physiologically in order to probe its effect on olfactory memory. In rats with bilateral bulbar cannulations, we show that these stressors modulate olfactory memory and that this effect is at least partially mediated by olfactory bulb. Specifically, we show that the presence of stressors during the acquisition of odor memory suppresses memory for an odor when tested 30 minutes after the acquisition. This suppression is blocked by infusing NE antagonists into the olfactory bulb prior to odor acquisition. Additionally, we find that infusion of bulbar NE is sufficient to suppress odor memory in a manner mimicking that of our stressors. These effects are unlikely to be solely mediated by locomotor/exploratory changes produced by stressors, although these stressors influence certain behaviors not directly related to odor investigation. This study provides important information about how behaviorally relevant changes in NE can influence top-down sensory processing and odor memory.

  2. Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

    Science.gov (United States)

    Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

    2015-11-01

    The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

  3. Sleep Dependent Memory Consolidation in Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Maski, Kiran; Holbrook, Hannah; Manoach, Dara; Hanson, Ellen; Kapur, Kush; Stickgold, Robert

    2015-12-01

    Examine the role of sleep in the consolidation of declarative memory in children with autism spectrum disorder (ASD). Case-control study. Home-based study with sleep and wake conditions. Twenty-two participants with ASD and 20 control participants between 9 and 16 y of age. Participants were trained to criterion on a spatial declarative memory task and then given a cued recall test. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with home-based polysomnography; Wake and Sleep conditions were counterbalanced. Children with ASD had poorer sleep efficiency than controls, but other sleep macroarchitectural and microarchitectural measures were comparable after controlling for age and medication use. Both groups demonstrated better memory consolidation across Sleep than Wake, although participants with ASD had poorer overall memory consolidation than controls. There was no interaction between group and condition. The change in performance across sleep, independent of medication and age, showed no significant relationships with any specific sleep parameters other than total sleep time and showed a trend toward less forgetting in the control group. This study shows that despite their more disturbed sleep quality, children with autism spectrum disorder (ASD) still demonstrate more stable memory consolidation across sleep than in wake conditions. The findings support the importance of sleep for stabilizing memory in children with and without neurodevelopmental disabilities. Our results suggest that improving sleep quality in children with ASD could have direct benefits to improving their overall cognitive functioning. © 2015 Associated Professional Sleep Societies, LLC.

  4. Factors that influence the relative use of multiple memory systems.

    Science.gov (United States)

    Packard, Mark G; Goodman, Jarid

    2013-11-01

    Neurobehavioral evidence supports the existence of at least two anatomically distinct "memory systems" in the mammalian brain that mediate dissociable types of learning and memory; a "cognitive" memory system dependent upon the hippocampus and a "stimulus-response/habit" memory system dependent upon the dorsolateral striatum. Several findings indicate that despite their anatomical and functional distinctiveness, hippocampal- and dorsolateral striatal-dependent memory systems may potentially interact and that, depending on the learning situation, this interaction may be cooperative or competitive. One approach to examining the neural mechanisms underlying these interactions is to consider how various factors influence the relative use of multiple memory systems. The present review examines several such factors, including information compatibility, temporal sequence of training, the visual sensory environment, reinforcement parameters, emotional arousal, and memory modulatory systems. Altering these parameters can lead to selective enhancements of either hippocampal-dependent or dorsolateral striatal-dependent memory, and bias animals toward the use of either cognitive or habit memory in dual-solution tasks that may be solved adequately with either memory system. In many learning situations, the influence of such experimental factors on the relative use of memory systems likely reflects a competitive interaction between the systems. Research examining how various factors influence the relative use of multiple memory systems may be a useful method for investigating how these systems interact with one another. Copyright © 2013 Wiley Periodicals, Inc.

  5. The radish gene reveals a memory component with variable temporal properties.

    Directory of Open Access Journals (Sweden)

    Holly LaFerriere

    Full Text Available Memory phases, dependent on different neural and molecular mechanisms, strongly influence memory performance. Our understanding, however, of how memory phases interact is far from complete. In Drosophila, aversive olfactory learning is thought to progress from short-term through long-term memory phases. Another memory phase termed anesthesia resistant memory, dependent on the radish gene, influences memory hours after aversive olfactory learning. How does the radish-dependent phase influence memory performance in different tasks? It is found that the radish memory component does not scale with the stability of several memory traces, indicating a specific recruitment of this component to influence different memories, even within minutes of learning.

  6. Memory and Self–Neuroscientific Landscapes

    Science.gov (United States)

    Markowitsch, Hans J.

    2013-01-01

    Relations between memory and the self are framed from a number of perspectives—developmental aspects, forms of memory, interrelations between memory and the brain, and interactions between the environment and memory. The self is seen as dividable into more rudimentary and more advanced aspects. Special emphasis is laid on memory systems and within them on episodic autobiographical memory which is seen as a pure human form of memory that is dependent on a proper ontogenetic development and shaped by the social environment, including culture. Self and episodic autobiographical memory are seen as interlocked in their development and later manifestation. Aside from content-based aspects of memory, time-based aspects are seen along two lines—the division between short-term and long-term memory and anterograde—future-oriented—and retrograde—past-oriented memory. The state dependency of episodic autobiographical is stressed and implications of it—for example, with respect to the occurrence of false memories and forensic aspects—are outlined. For the brain level, structural networks for encoding, consolidation, storage, and retrieval are discussed both by referring to patient data and to data obtained in normal participants with functional brain imaging methods. It is elaborated why descriptions from patients with functional or dissociative amnesia are particularly apt to demonstrate the facets in which memory, self, and personal temporality are interwoven. PMID:24967303

  7. The Effect of Opium Dependency of Parent (s on Offspring’s Spatial Learning & Memory in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Arezoo Saberi Moghadam

    2013-05-01

    Full Text Available Objective(s:As far as we know,there has been no report regarding the effects of opium addiction or dependency of both parents on the learning and memory process in offspring. The aim of this study was to examine the learning and memory changes of adult male offspring whose mothers, fathers and/or both parents had dependency to opium before and during pregnancy. Materials and Methods: All experiments were carried out on Wistar rats. Opium dependency was induced by daily injections of opium (10 mg/kg/SC, bid/10 d before mating. The presence of a vaginal plug was designated as gestation day. Treatment with opium continued through breeding and gestation until parturition. Spatial memory was tested in male offspring of control, saline and prenatal opium treated groups by a training trial and the probe test in the Morris water maze. Swimming escape latency in the maze and the ability to find the platform in the training trial were recorded. The time spent in the trigger zone and number of times the rats crossed the platform during the probe phase and swimming speed were measured. Results:Thedata revealed increased escape latency and a greater distance traveled to find the hidden platform in the offspring’s whose mother, father and /or both parents were exposed to opium. Crossings to target quadrant at probe trials was significantly reduced in all of the prenatal opium exposed offsprings. The swimming speed showed a significant increase in father and parent’s opium exposed offspring.  Conclusion:Prenatal opium exposure of either parent may cause deficits in spatial learning, but the precise mechanism(s remain largely unknown.

  8. Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics.

    Science.gov (United States)

    Lukas, Michael; Toth, Iulia; Veenema, Alexa H; Neumann, Inga D

    2013-06-01

    Brain oxytocin (OXT) plays an important role in short-term social memory in laboratory rodents. Here we monitored local release of OXT and its functional involvement in the maintenance and retrieval of social memory during the social discrimination test. We further assessed, if the local effects of OXT within the medial amygdala (MeA) and lateral septum (LS) on social discrimination abilities were dependent on the biological relevance of the social stimulus, thus comparing male juvenile versus adult female conspecifics. OXT release was increased in the LS of male rats during the retrieval, but not during the acquisition or maintenance, of social memory for male juvenile stimuli. Blockade of OXT activity by intracerebroventricular (ICV) administration of a specific OXT receptor antagonist (OXTR-A, rats: 0.75 μg/5 μl, mice: 2 μg/2 μl) immediately after acquisition of social memory impaired the maintenance of social memory, and consequently discrimination abilities during retrieval of social memory. In contrast, ICV OXTR-A was without effect when administered 20 min prior to retrieval of social memory in both species. Non-social memory measured in the object discrimination test was not affected by ICV OXTR-A in male mice, indicating that brain OXT is mainly required for memory formation in a social context. The biological relevance of the social stimulus seems to importantly determine social memory abilities, as male rats recognized a previously encountered female adult stimulus for at least 2h (versus 60 min for male juveniles), with a region-dependent contribution of endogenous OXT; while bilateral administration of OXTR-A into the MeA (0.1 μg/1 μl) impaired social memory for adult females only, administration of OXTR-A into the LS via retrodialysis (10 μg/ml, 1.0 μl/min) impaired social memory for both male juveniles and female adults. Overall, these results indicate that brain OXT is a critical mediator of social memory in male rodents and that, depending

  9. Memory behaviors of entropy production rates in heat conduction

    Science.gov (United States)

    Li, Shu-Nan; Cao, Bing-Yang

    2018-02-01

    Based on the relaxation time approximation and first-order expansion, memory behaviors in heat conduction are found between the macroscopic and Boltzmann-Gibbs-Shannon (BGS) entropy production rates with exponentially decaying memory kernels. In the frameworks of classical irreversible thermodynamics (CIT) and BGS statistical mechanics, the memory dependency on the integrated history is unidirectional, while for the extended irreversible thermodynamics (EIT) and BGS entropy production rates, the memory dependences are bidirectional and coexist with the linear terms. When macroscopic and microscopic relaxation times satisfy a specific relationship, the entropic memory dependences will be eliminated. There also exist initial effects in entropic memory behaviors, which decay exponentially. The second-order term are also discussed, which can be understood as the global non-equilibrium degree. The effects of the second-order term are consisted of three parts: memory dependency, initial value and linear term. The corresponding memory kernels are still exponential and the initial effects of the global non-equilibrium degree also decay exponentially.

  10. A Chinese text classification system based on Naive Bayes algorithm

    Directory of Open Access Journals (Sweden)

    Cui Wei

    2016-01-01

    Full Text Available In this paper, aiming at the characteristics of Chinese text classification, using the ICTCLAS(Chinese lexical analysis system of Chinese academy of sciences for document segmentation, and for data cleaning and filtering the Stop words, using the information gain and document frequency feature selection algorithm to document feature selection. Based on this, based on the Naive Bayesian algorithm implemented text classifier , and use Chinese corpus of Fudan University has carried on the experiment and analysis on the system.

  11. Dependence of Immunoglobulin Class Switch Recombination in B Cells on Vesicular Release of ATP and CD73 Ectonucleotidase Activity

    Directory of Open Access Journals (Sweden)

    Francesca Schena

    2013-06-01

    Full Text Available Immunoglobulin (Ig isotype diversification by class switch recombination (CSR is an essential process for mounting a protective humoral immune response. Ig CSR deficiencies in humans can result from an intrinsic B cell defect; however, most of these deficiencies are still molecularly undefined and diagnosed as common variable immunodeficiency (CVID. Here, we show that extracellular adenosine critically contributes to CSR in human naive and IgM memory B cells. In these cells, coordinate stimulation of B cell receptor and toll-like receptors results in the release of ATP stored in Ca2+-sensitive secretory vesicles. Plasma membrane ectonucleoside triphosphate diphosphohydrolase 1 CD39 and ecto-5′-nucleotidase CD73 hydrolyze ATP to adenosine, which induces CSR in B cells in an autonomous fashion. Notably, CVID patients with impaired class-switched antibody responses are selectively deficient in CD73 expression in B cells, suggesting that CD73-dependent adenosine generation contributes to the pathogenesis of this disease.

  12. DeNASA: Destination-Naive AS-Awareness in Anonymous Communications

    Directory of Open Access Journals (Sweden)

    Barton Armon

    2016-10-01

    Full Text Available Prior approaches to AS-aware path selection in Tor do not consider node bandwidth or the other characteristics that Tor uses to ensure load balancing and quality of service. Further, since the AS path from the client’s exit to her destination can only be inferred once the destination is known, the prior approaches may have problems constructing circuits in advance, which is important for Tor performance. In this paper, we propose and evaluate DeNASA, a new approach to AS-aware path selection that is destination-naive, in that it does not need to know the client’s destination to pick paths, and that takes advantage of Tor’s circuit selection algorithm. To this end, we first identify the most probable ASes to be traversed by Tor streams. We call this set of ASes the Suspect AS list and find that it consists of eight highest ranking Tier 1 ASes. Then, we test the accuracy of Qiu and Gao AS-level path inference on identifying the presence of these ASes in the path, and we show that inference accuracy is 90%. We develop an AS-aware algorithm called DeNASA that uses Qiu and Gao inference to avoid Suspect ASes. DeNASA reduces Tor stream vulnerability by 74%. We also show that DeNASA has performance similar to Tor. Due to the destination-naive property, time to first byte (TTFB is close to Tor’s, and due to leveraging Tor’s bandwidth-weighted relay selection, time to last byte (TTLB is also similar to Tor’s.

  13. Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression.

    Science.gov (United States)

    Lim, Patrick H; Wert, Stephanie L; Tunc-Ozcan, Elif; Marr, Robert; Ferreira, Adriana; Redei, Eva E

    2018-02-25

    Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Menstrual-cycle dependent fluctuations in ovarian hormones affect emotional memory.

    Science.gov (United States)

    Bayer, Janine; Schultz, Heidrun; Gamer, Matthias; Sommer, Tobias

    2014-04-01

    The hormones progesterone and estradiol modulate neural plasticity in the hippocampus, the amygdala and the prefrontal cortex. These structures are involved in the superior memory for emotionally arousing information (EEM effects). Therefore, fluctuations in hormonal levels across the menstrual cycle are expected to influence activity in these areas as well as behavioral memory performance for emotionally arousing events. To test this hypothesis, naturally cycling women underwent functional magnetic resonance imaging during the encoding of emotional and neutral stimuli in the low-hormone early follicular and the high-hormone luteal phase. Their memory was tested after an interval of 48 h, because emotional arousal primarily enhances the consolidation of new memories. Whereas overall recognition accuracy remained stable across cycle phases, recognition quality varied with menstrual cycle phases. Particularly recollection-based recognition memory for negative items tended to decrease from early follicular to luteal phase. EEM effects for both valences were associated with higher activity in the right anterior hippocampus during early follicular compared to luteal phase. Valence-specific modulations were found in the anterior cingulate, the amygdala and the posterior hippocampus. Current findings connect to anxiolytic actions of estradiol and progesterone as well as to studies on fear conditioning. Moreover, they are in line with differential networks involved in EEM effects for positive and negative items. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cognitive control over memory - individual differences in memory performance for emotional and neutral material.

    Science.gov (United States)

    Wierzba, M; Riegel, M; Wypych, M; Jednoróg, K; Grabowska, A; Marchewka, A

    2018-02-28

    It is widely accepted that people differ in memory performance. The ability to control one's memory depends on multiple factors, including the emotional properties of the memorized material. While it was widely demonstrated that emotion can facilitate memory, it is unclear how emotion modifies our ability to suppress memory. One of the reasons for the lack of consensus among researchers is that individual differences in memory performance were largely neglected in previous studies. We used the directed forgetting paradigm in an fMRI study, in which subjects viewed neutral and emotional words, which they were instructed to remember or to forget. Subsequently, subjects' memory of these words was tested. Finally, they assessed the words on scales of valence, arousal, sadness and fear. We found that memory performance depended on instruction as reflected in the engagement of the lateral prefrontal cortex (lateral PFC), irrespective of emotional properties of words. While the lateral PFC engagement did not differ between neutral and emotional conditions, it correlated with behavioural performance when emotional - as opposed to neutral - words were presented. A deeper understanding of the underlying brain mechanisms is likely to require a study of individual differences in cognitive abilities to suppress memory.

  16. CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent.

    Science.gov (United States)

    D'Souza, Lucas; Gupta, Sneh Lata; Bal, Vineeta; Rath, Satyajit; George, Anna

    2017-12-01

    B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM + cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73 + IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory. © 2017 John Wiley & Sons Ltd.

  17. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    NARCIS (Netherlands)

    Fleischmann, Roy M.; Huizinga, Tom W. J.; Kavanaugh, Arthur F.; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F.

    2016-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult

  18. Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis

    International Nuclear Information System (INIS)

    Kim, Joong-Sun; Lee, Hae-June; Kim, Jong-Choon

    2008-01-01

    Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis. (author)

  19. Acetylation-mediated suppression of transcription-independent memory: bidirectional modulation of memory by acetylation.

    Directory of Open Access Journals (Sweden)

    Katja Merschbaecher

    Full Text Available Learning induced changes in protein acetylation, mediated by histone acetyl transferases (HATs, and the antagonistic histone deacetylases (HDACs play a critical role in memory formation. The status of histone acetylation affects the interaction between the transcription-complex and DNA and thus regulates transcription-dependent processes required for long-term memory (LTM. While the majority of studies report on the role of elevated acetylation in memory facilitation, we address the impact of both, increased and decreased acetylation on formation of appetitive olfactory memory in honeybees. We show that learning-induced changes in the acetylation of histone H3 at aminoacid-positions H3K9 and H3K18 exhibit distinct and different dynamics depending on the training strength. A strong training that induces LTM leads to an immediate increase in acetylation at H3K18 that stays elevated for hours. A weak training, not sufficient to trigger LTM, causes an initial increase in acetylation at H3K18, followed by a strong reduction in acetylation at H3K18 below the control group level. Acetylation at position H3K9 is not affected by associative conditioning, indicating specific learning-induced actions on the acetylation machinery. Elevating acetylation levels by blocking HDACs after conditioning leads to an improved memory. While memory after strong training is enhanced for at least 2 days, the enhancement after weak training is restricted to 1 day. Reducing acetylation levels by blocking HAT activity after strong training leads to a suppression of transcription-dependent LTM. The memory suppression is also observed in case of weak training, which does not require transcription processes. Thus, our findings demonstrate that acetylation-mediated processes act as bidirectional regulators of memory formation that facilitate or suppress memory independent of its transcription-requirement.

  20. About sleep's role in memory.

    Science.gov (United States)

    Rasch, Björn; Born, Jan

    2013-04-01

    Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.

  1. Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

    Science.gov (United States)

    Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

    2015-01-01

    Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P dyslipidemia characterized by high TG and low HDL, which was associated with lower CD4 counts. These data support the assessment of lipid profiles before and after initiation of antiretroviral therapy regardless of age. PMID:26632908

  2. Memory reconsolidation mediates the updating of hippocampal memory content

    Directory of Open Access Journals (Sweden)

    Jonathan L C Lee

    2010-11-01

    Full Text Available The retrieval or reactivation of a memory places it into a labile state, requiring a process of reconsolidation to restabilize it. This retrieval-induced plasticity is a potential mechanism for the modification of the existing memory. Following previous data supportive of a functional role for memory reconsolidation in the modification of memory strength, here I show that hippocampal memory reconsolidation also supports the updating of contextual memory content. Using a procedure that separates the learning of pure context from footshock-motivated contextual fear learning, I demonstrate doubly dissociable hippocampal mechanisms of initial context learning and subsequent updating of the neutral contextual representation to incorporate the footshock. Contextual memory consolidation was dependent upon BDNF expression in the dorsal hippocampus, whereas the footshock modification of the contextual representation required the expression of Zif268. These mechanisms match those previously shown to be selectively involved in hippocampal memory consolidation and reconsolidation, respectively. Moreover, memory reactivation is a necessary step in modifying memory content, as inhibition of hippocampal synaptic protein degradation also prevented the footshock-mediated memory modification. Finally, dorsal hippocampal knockdown of Zif268 impaired the reconsolidation of the pure contextual memory only under conditions of weak context memory training, as well as failing to disrupt contextual freezing when a strong contextual fear memory is reactivated by further conditioning. Therefore, an adaptive function of the reactivation and reconsolidation process is to enable the updating of memory content.

  3. Human memory search

    NARCIS (Netherlands)

    Davelaar, E.J.; Raaijmakers, J.G.W.; Hills, T.T.; Robbins, T.W.; Todd, P.M.

    2012-01-01

    The importance of understanding human memory search is hard to exaggerate: we build and live our lives based on what whe remember. This chapter explores the characteristics of memory search, with special emphasis on the use of retrieval cues. We introduce the dependent measures that are obtained

  4. Change of entropy in the martensitic transformation and its dependence in Cu-based shape memory alloys

    International Nuclear Information System (INIS)

    Romero, R.; Pelegrina, J.L.

    2003-01-01

    A study of the entropy change ΔS between the β phase and the martensite in Cu-based shape memory alloys is presented. From a compilation of available experimental data, the composition dependence of ΔS was studied. The experimental data were analyzed within the frame of a simple model, which is based on the specific heats of the phases. It was demonstrated that the dependence of ΔS with composition comes only through the lattice parameter and the effective mass of the alloy. For the studied composition range, the greater vibrational entropy of β phase is mainly controlled by the high-mass Cu atoms

  5. Declarative and nondeclarative memory: multiple brain systems supporting learning and memory.

    Science.gov (United States)

    Squire, L R

    1992-01-01

    Abstract The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).

  6. Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

    Science.gov (United States)

    Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

    2012-10-01

    The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

  7. The Effect of Dorsal Hippocampal α2-Adrenegic Receptors on WIN55,212-2 State-Dependent Memory of Passive Avoidance

    Directory of Open Access Journals (Sweden)

    Zarrindast M.R.

    2010-09-01

    Full Text Available Background and Objectives: Cannabinoids are a class of psychoactive compounds that produce a wide array of effects in a large number of species. In the present study, the effects of bilateral intra-CA1 injections of an α2-adrenergic receptor agents, on WIN55,212-2 state-dependent learning were examined in adult male Wistar rats. Methods: The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-down type inhibitory avoidance task, and tested 24h after training to measure step-down latency.Results: Post-training intra-CA1 injection of WIN55,212-2 (0.25 and 0.5µg/rat induced impairment of memory retention. Amnesia produced by post-training WIN55,212-2 (0.5µg/rat was reversed by pre-test administration of the same dose of WIN55,212-2 that is due to a state-dependent effect. Pre-test intra-CA1 injection of clonidine (0.5 and 0.75µg/rat, intra-CA1 improved post-training WIN55,212-2 (0.5µg/rat, intra-CA1-induced retrieval impairment, while pre-test intra-CA1 injection of yohimbine (1µg/rat, intra-CA1 2min before the administration of WIN55,212-2 (0.5µg/rat, intra-CA1 inhibited WIN55,212-2 state-dependent memory. Conclusion: These results suggest that α2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in Win55,212-2-induced amnesia and WIN55,212-2 state-dependent memory.

  8. Diet-induced obesity does not impact the generation and maintenance of primary memory CD8 T cells.

    Science.gov (United States)

    Khan, Shaniya H; Hemann, Emily A; Legge, Kevin L; Norian, Lyse A; Badovinac, Vladimir P

    2014-12-15

    The extent to which obesity compromises the differentiation and maintenance of protective memory CD8 T cell responses and renders obese individuals susceptible to infection remains unknown. In this study, we show that diet-induced obesity did not impact the maintenance of pre-existing memory CD8 T cells, including acquisition of a long-term memory phenotype (i.e., CD27(hi), CD62L(hi), KLRG1(lo)) and function (i.e., cytokine production, secondary expansion, and memory CD8 T cell-mediated protection). Additionally, obesity did not influence the differentiation and maintenance of newly evoked memory CD8 T cell responses in inbred and outbred hosts generated in response to different types of systemic (LCMV, L. monocytogenes) and/or localized (influenza virus) infections. Interestingly, the rate of naive-to-memory CD8 T cell differentiation after a peptide-coated dendritic cell immunization was similar in lean and obese hosts, suggesting that obesity-associated inflammation, unlike pathogen- or adjuvant-induced inflammation, did not influence the development of endogenous memory CD8 T cell responses. Therefore, our studies reveal that the obese environment does not influence the development or maintenance of memory CD8 T cell responses that are either primed before or after obesity is established, a surprising notion with important implications for future studies aiming to elucidate the role obesity plays in host susceptibility to infections. Copyright © 2014 by The American Association of Immunologists, Inc.

  9. About Sleep's Role in Memory

    Science.gov (United States)

    2013-01-01

    Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of “sleep and memory” research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems. PMID:23589831

  10. Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study

    Science.gov (United States)

    Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

    2010-01-01

    Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

  11. Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.

    Science.gov (United States)

    Velásquez, Sonia Y; García, Luis F; Opelz, Gerhard; Alvarez, Cristiam M; Süsal, Caner

    2013-07-27

    Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation. We investigated the kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched controls. Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4 cells (PCD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (PsCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls. Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T cells and increased release of sCD30 from these cells in an IFN-γ- and IL-2-dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ- and IL-2-producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.

  12. Nonlocal superelastic model of size-dependent hardening and dissipation in single crystal Cu-Al-Ni shape memory alloys.

    Science.gov (United States)

    Qiao, Lei; Rimoli, Julian J; Chen, Ying; Schuh, Christopher A; Radovitzky, Raul

    2011-02-25

    We propose a nonlocal continuum model to describe the size-dependent superelastic effect observed in recent experiments of single crystal Cu-Al-Ni shape memory alloys. The model introduces two length scales, one in the free energy and one in the dissipation, which account for the size-dependent hardening and dissipation in the loading and unloading response of micro- and nanopillars subject to compression tests. The information provided by the model suggests that the size dependence observed in the dissipation is likely to be associated with a nonuniform evolution of the distribution of the austenitic and martensitic phases during the loading cycle. © 2011 American Physical Society

  13. Context-Dependent Repetition Effects on Recognition Memory

    Science.gov (United States)

    Opitz, Bertram

    2010-01-01

    One widely acknowledged way to improve our memory performance is to repeatedly study the to be learned material. One aspect that has received little attention in past research regards the context sensitivity of this repetition effect, that is whether the item is repeated within the same or within different contexts. The predictions of a…

  14. Protein Synthesis-Dependent Long-Term Memory Induced by One Single Associative Training Trial in the Parasitic Wasp Lariophagus distinguendus

    Science.gov (United States)

    Steidle, Johannes L. M.; Collatz, Jana; Muller, Caroline

    2006-01-01

    Protein synthesis-dependent long-term memory in Apis mellifera and Drosophila melanogaster is formed after multiple trainings that are spaced in time. The parasitic wasp Lariophagus distinguendus remarkably differs from these species. It significantly responds to the artificial odor furfurylheptanoate (FFH) in olfactometer experiments, when this…

  15. Consciousness: physiological dependence on rapid memory access.

    Science.gov (United States)

    Hudson, Arthur J

    2009-01-01

    Consciousness develops from birth during the early months as the senses and other nervous system functions mature sufficiently to receive, process and store information. Among these is the ascending reticular activating (arousal) system in the brain stem that is responsible for wakefulness and was proposed by Penfield and Jasper more than 50 years ago as the "controlling mechanism for states of consciousness". This concept has remained the most advanced physiological interpretation of consciousness although recent developments offer greater insights into its nature. The ascending arousal system is the source of activation of the thalamocortical and cortical mechanisms for sensory input and facilitates the rapid matching of sensory input and the binding of memory during cognitive processing. Nonetheless, it is proposed that memory is the critical element through which our connection with the world exists without which, despite a fully functional arousal system, consciousness as we know it could not exist. Evidence is presented in support of this concept in addition to the physiological difficulties that must be resolved if consciousness is to be understood.

  16. Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART.

    Science.gov (United States)

    Ono, E; Nunes dos Santos, A M; de Menezes Succi, R C; Machado, D M; de Angelis, D S A; Salomão, R; Kallás, E G; de Moraes-Pinto, M I

    2008-08-01

    The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

  17. Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory.

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C

    2016-11-23

    The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin- and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also expressed in some hippocampal neurons, but its functional role in the brain is unclear. Several established molecular modulators of memory processing regulate hippocampal GluT4 trafficking and hippocampal memory formation is limited by both glucose metabolism and insulin signaling. Therefore, we hypothesized that hippocampal GluT4 might be involved in memory processes. Here, we show that, in male rats, hippocampal GluT4 translocates to the plasma membrane after memory training and that acute, selective intrahippocampal inhibition of GluT4-mediated glucose transport impaired memory acquisition, but not memory retrieval. Other studies have shown that prolonged systemic GluT4 blockade causes insulin resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose transport through GluT4-upregulated markers of hippocampal insulin signaling prevented task-associated depletion of hippocampal glucose and enhanced both working and short-term memory while also impairing long-term memory. These effects were accompanied by increased expression of hippocampal AMPA GluR1 subunits and the neuronal GluT3, but decreased expression of hippocampal brain-derived neurotrophic factor, consistent with impaired ability to form long-term memories. Our findings are the first to show the cognitive impact of brain GluT4 modulation. They identify GluT4 as a key regulator of hippocampal memory processing and also suggest differential regulation of GluT4 in the hippocampus from that in peripheral tissues. The role of insulin-regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current study, we demonstrate that GluT4 is a critical component of hippocampal memory processes. Memory training increased hippocampal GluT4 translocation and memory acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long

  18. Hardware Compilation of Application-Specific Memory-Access Interconnect

    DEFF Research Database (Denmark)

    Venkataramani, Girish; Bjerregaard, Tobias; Chelcea, Tiberiu

    2006-01-01

    operations dependent on memory reads. More fundamental is that dependences between accesses may not be statically provable (e.g., if the specification language permits pointers), which introduces memory-consistency problems. Addressing these issues with static scheduling results in overly conservative...... enables specifications to include arbitrary memory references (e.g., pointers) and allows the memory system to incorporate features that might cause the latency of a memory access to vary dynamically. This results in raising the level of abstraction in the input specification, enabling faster design times...

  19. KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

    Science.gov (United States)

    Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

    2018-04-10

    Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Naive Bayes as opinion classifier to evaluate students satisfaction based on student sentiment in Twitter Social Media

    Science.gov (United States)

    Candra Permana, Fahmi; Rosmansyah, Yusep; Setiawan Abdullah, Atje

    2017-10-01

    Students activity on social media can provide implicit knowledge and new perspectives for an educational system. Sentiment analysis is a part of text mining that can help to analyze and classify the opinion data. This research uses text mining and naive Bayes method as opinion classifier, to be used as an alternative methods in the process of evaluating studentss satisfaction for educational institution. Based on test results, this system can determine the opinion classification in Bahasa Indonesia using naive Bayes as opinion classifier with accuracy level of 84% correct, and the comparison between the existing system and the proposed system to evaluate students satisfaction in learning process, there is only a difference of 16.49%.

  1. Targeted Memory Reactivation during Sleep Depends on Prior Learning.

    Science.gov (United States)

    Creery, Jessica D; Oudiette, Delphine; Antony, James W; Paller, Ken A

    2015-05-01

    When sounds associated with learning are presented again during slow-wave sleep, targeted memory reactivation (TMR) can produce improvements in subsequent location recall. Here we used TMR to investigate memory consolidation during an afternoon nap as a function of prior learning. Twenty healthy individuals (8 male, 19-23 y old). Participants learned to associate each of 50 common objects with a unique screen location. When each object appeared, its characteristic sound was played. After electroencephalography (EEG) electrodes were applied, location recall was assessed for each object, followed by a 90-min interval for sleep. During EEG-verified slow-wave sleep, half of the sounds were quietly presented over white noise. Recall was assessed 3 h after initial learning. A beneficial effect of TMR was found in the form of higher recall accuracy for cued objects compared to uncued objects when pre-sleep accuracy was used as an explanatory variable. An analysis of individual differences revealed that this benefit was greater for participants with higher pre-sleep recall accuracy. In an analysis for individual objects, cueing benefits were apparent as long as initial recall was not highly accurate. Sleep physiology analyses revealed that the cueing benefit correlated with delta power and fast spindle density. These findings substantiate the use of targeted memory reactivation (TMR) methods for manipulating consolidation during sleep. TMR can selectively strengthen memory storage for object-location associations learned prior to sleep, except for those near-perfectly memorized. Neural measures found in conjunction with TMR-induced strengthening provide additional evidence about mechanisms of sleep consolidation. © 2015 Associated Professional Sleep Societies, LLC.

  2. Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Hans; Erritzoe, David; Andersen, Rune

    2010-01-01

    , in vivo studies of serotonin(2A) binding report conflicting results, presumably because sample sizes have been small or because schizophrenic patients who were not antipsychotic-naive were included. Furthermore, the relationships between serotonin(2A) binding, psychopathology, and central neurocognitive...

  3. Time-dependent effects of cortisol on the contextualization of emotional memories

    NARCIS (Netherlands)

    van Ast, V.A.; Cornelisse, S.; Meeter, M.; Joëls, M.; Kindt, M.

    2013-01-01

    Background: The inability to store fearful memories into their original encoding context is considered to be an important vulnerability factor for the development of anxiety disorders like posttraumatic stress disorder. Altered memory contextualization most likely involves effects of the stress

  4. Providing probability distributions for the causal pathogen of clinical mastitis using naive Bayesian networks

    NARCIS (Netherlands)

    Steeneveld, W.; Gaag, van der L.C.; Barkema, H.W.; Hogeveen, H.

    2009-01-01

    Clinical mastitis (CM) can be caused by a wide variety of pathogens and farmers must start treatment before the actual causal pathogen is known. By providing a probability distribution for the causal pathogen, naive Bayesian networks (NBN) can serve as a management tool for farmers to decide which

  5. IFN-Gamma-Dependent and Independent Mechanisms of CD4⁺ Memory T Cell-Mediated Protection from Listeria Infection.

    Science.gov (United States)

    Meek, Stephanie M; Williams, Matthew A

    2018-02-13

    While CD8⁺ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4⁺ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV), followed by a heterologous rechallenge with Listeria monocytogenes recombinantly expressing the MHC Class II-restricted LCMV epitope, GP 61-80 (Lm-gp61). We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4⁺ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4⁺ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4⁺ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4⁺ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4⁺ memory T cells from heterologous Listeria challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role.

  6. Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8+ T Cells in a Diameter-Dependent Manner.

    Science.gov (United States)

    Karuturi, Bala V K; Tallapaka, Shailendra B; Yeapuri, Pravin; Curran, Stephen M; Sanderson, Sam D; Vetro, Joseph A

    2017-05-01

    The diameter of biodegradable particles used to coencapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8 + T cells generated by systemic immunization. Possible effects on the magnitude of CD8 + T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles. We then compared total magnitude, effector/central memory (CD127/KRLG1/CD62L), and IFN-γ/TNF-α/IL-2 secreting subsets of pp89-specific CD8 + T cells as well as protection of naive female BALB/c mice against primary respiratory infection with MCMV 21 days after respiratory immunization. We found that decreasing the diameter of encapsulating particle from ∼5.4 μm to ∼350 nm (i) increased the magnitude of pp89-specific CD8 + T cells in the lungs and spleen; (ii) partially changed CD127/KLRG1 effector memory subsets in the lungs but not the spleen; (iii) changed CD127/KRLG1/CD62L effector/central memory subsets in the spleen; (iv) changed pp89-responsive IFN-γ/TNF-α/IL-2 secreting subsets in the lungs and spleen; (v) did not affect the extent to which encapsulation increased efficacy against primary MCMV respiratory infection over unencapsulated pp89-RR-EP67. Thus, although not observed under our current experimental conditions with MCMV, varying the diameter of nanoscale biodegradable particles may increase the efficacy of mucosal immunization with coencapsulated immunostimulant/subunit vaccines against certain pathogens by selectively increasing memory subset(s) of CD8 + T cells that correlate the strongest with protection.

  7. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia.

    Science.gov (United States)

    Janikashvili, Nona; LaCasse, Collin J; Larmonier, Claire; Trad, Malika; Herrell, Amanda; Bustamante, Sara; Bonnotte, Bernard; Har-Noy, Michael; Larmonier, Nicolas; Katsanis, Emmanuel

    2011-02-03

    Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4(+)CD25(+)FoxP3(+) regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3(+) Tregs from naive CD4(+)CD25(-)FoxP3(-) T cells by an interferon-γ-dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.

  8. Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients.

    Science.gov (United States)

    Vandekerckhove, Linos; Verhofstede, Chris; Vogelaers, Dirk

    2009-06-01

    Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the USA) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire approval by the US Food and Drug Administration and the European Medicine Agency. Considering the mechanism of action, it is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring the R5 virus. The favourable toxicity profile of the drug has been demonstrated in Phase III clinical trials in treatment-naive (MERIT) and treatment-experienced (MOTIVATE) patients. In the latter population, maraviroc showed a superior antiviral efficacy and immunological activity compared with optimized backbone therapy + placebo. However, in MERIT, a prospective double-blind, randomized trial in treatment-naive patients, maraviroc + zidovudine/lamivudine failed to prove non-inferiority to efavirenz + zidovudine/lamivudine as standard of care regimen in the 48 week intention-to-treat analysis. Using an assay with higher sensitivity for minority CXCR4-using (X4) HIV variants (the enhanced Trofile assay-Monogram), non-inferiority was reached for the maraviroc- versus efavirenz-based combination. These data indicate the important impact of the sensitivity of tropism testing on treatment outcome of maraviroc-containing regimens. This paper discusses both the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on daily practice in HIV care.

  9. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    International Nuclear Information System (INIS)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-01-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[ 14 C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14 CO 2 excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an α 2 -adrenergic agonist

  10. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  11. Hippocampal function is not required for the precision of remote place memory

    Directory of Open Access Journals (Sweden)

    Kitamura Takashi

    2012-02-01

    Full Text Available Abstract Background During permanent memory formation, recall of acquired place memories initially depends on the hippocampus and eventually become hippocampus-independent with time. It has been suggested that the quality of original place memories also transforms from a precise form to a less precise form with similar time course. The question arises of whether the quality of original place memories is determined by brain regions on which the memory depends. Results To directly test this idea, we introduced a new procedure: a non-associative place recognition memory test in mice. Combined with genetic and pharmacological approaches, our analyses revealed that place memory is precisely maintained for 28 days, although the recall of place memory shifts from hippocampus-dependent to hippocampus-independent with time. Moreover, the inactivation of the hippocampal function does not inhibit the precision of remote place memory. Conclusion These results indicate that the quality of place memories is not determined by brain regions on which the memory depends.

  12. From the trajectory to the density memory

    International Nuclear Information System (INIS)

    Cakir, Rasit; Krokhin, Arkadii; Grigolini, Paolo

    2007-01-01

    In this paper we discuss the connection between trajectory and density memory. The first form of memory is a property of a stochastic trajectory, whose stationary correlation function shows that the fluctuation at a given time depends on the earlier fluctuations. The density memory is a property of a collection of trajectories, whose density time evolution is described by a time convoluted equation showing that the density time evolution depends on its past history. We show that the trajectory memory does not necessarily yields density memory, and that density memory might be compatible with the existence of abrupt jumps resetting to zero the system's memory. We focus our attention on a time-convoluted diffusion equation, when the memory kernel is an inverse power law with (i) negative and (ii) positive tail. In case (i) there exist both renewal trajectories and trajectories with memory, compatible with this equation. Case (ii), which has eluded so far a convincing interpretation in terms of trajectories, is shown to be compatible only with trajectory memory

  13. Memory effects, two color percolation, and the temperature dependence of Mott variable-range hopping

    Science.gov (United States)

    Agam, Oded; Aleiner, Igor L.

    2014-06-01

    There are three basic processes that determine hopping transport: (a) hopping between normally empty sites (i.e., having exponentially small occupation numbers at equilibrium), (b) hopping between normally occupied sites, and (c) transitions between normally occupied and unoccupied sites. In conventional theories all these processes are considered Markovian and the correlations of occupation numbers of different sites are believed to be small (i.e., not exponential in temperature). We show that, contrary to this belief, memory effects suppress the processes of type (c) and manifest themselves in a subleading exponential temperature dependence of the variable-range hopping conductivity. This temperature dependence originates from the property that sites of type (a) and (b) form two independent resistor networks that are weakly coupled to each other by processes of type (c). This leads to a two-color percolation problem which we solve in the critical region.

  14. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study

    DEFF Research Database (Denmark)

    Lundgren, Jens; Emery, Sean; Neuhaus, Jacqueline A

    2008-01-01

    BACKGROUND: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group......, participants started ART when the CD4+ cell count was ART at entry inform the early use of ART. METHODS: Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following......). RESULTS: A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4...

  15. What drives sleep-dependent memory consolidation: greater gain or less loss?

    Science.gov (United States)

    Fenn, Kimberly M; Hambrick, David Z

    2013-06-01

    When memory is tested after a delay, performance is typically better if the retention interval includes sleep. However, it is unclear what accounts for this well-established effect. It is possible that sleep enhances the retrieval of information, but it is also possible that sleep protects against memory loss that normally occurs during waking activity. We developed a new research approach to investigate these possibilities. Participants learned a list of paired-associate items and were tested on the items after a 12-h interval that included waking or sleep. We analyzed the number of items gained versus the number of items lost across time. The sleep condition showed more items gained and fewer items lost than did the wake condition. Furthermore, the difference between the conditions (favoring sleep) in lost items was greater than the difference in gain, suggesting that loss prevention may primarily account for the effect of sleep on declarative memory consolidation. This finding may serve as an empirical constraint on theories of memory consolidation.

  16. Search of associative memory.

    NARCIS (Netherlands)

    Raaijmakers, J.G.W.; Shiffrin, R.M.

    1981-01-01

    Describes search of associative memory (SAM), a general theory of retrieval from long-term memory that combines features of associative network models and random search models. It posits cue-dependent probabilistic sampling and recovery from an associative network, but the network is specified as a

  17. Memory effects on stochastic resonance

    Science.gov (United States)

    Neiman, Alexander; Sung, Wokyung

    1996-02-01

    We study the phenomenon of stochastic resonance (SR) in a bistable system with internal colored noise. In this situation the system possesses time-dependent memory friction connected with noise via the fluctuation-dissipation theorem, so that in the absence of periodic driving the system approaches the thermodynamic equilibrium state. For this non-Markovian case we find that memory usually suppresses stochastic resonance. However, for a large memory time SR can be enhanced by the memory.

  18. Remaking memories: reconsolidation updates positively motivated spatial memory in rats.

    Science.gov (United States)

    Jones, Bethany; Bukoski, Elizabeth; Nadel, Lynn; Fellous, Jean-Marc

    2012-02-17

    There is strong evidence that reactivation of a memory returns it to a labile state, initiating a restabilization process termed reconsolidation, which allows for updating of the memory. In this study we investigated reactivation-dependent updating using a new positively motivated spatial task in rodents that was designed specifically to model a human list-learning paradigm. On Day 1, rats were trained to run to three feeders (List 1) for rewards. On Day 2, rats were trained to run to three different feeders (List 2) in either the same (Reminder condition) or a different (No Reminder condition) experimental context than on Day 1. On Day 3, rats were cued to recall List 1. Rats in the Reminder condition made significantly more visits to List 2 feeders (intrusions) during List 1 recall than rats in the No Reminder condition, indicating that the reminder triggered reactivation and allowed integration of List 2 items into List 1. This reminder effect was selective for the reactivated List 1 memory, as no intrusions occurred when List 2 was recalled on Day 3. No intrusions occurred when retrieval took place in a different context from the one used at encoding, indicating that the expression of the updated memory is dependent upon the retrieval context. Finally, the level of intrusions was highest when retrieval took place immediately after List 2 learning, and generally declined when retrieval occurred 1-4 h later, indicating that the List 2 memory competed with short-term retrieval of List 1. These results demonstrate the dynamic nature of memory over time and the impact of environmental context at different stages of memory processing.

  19. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled...... was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow-up examinations (P Macular thickness improved significantly at all time...

  20. Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

    Directory of Open Access Journals (Sweden)

    Hubert Barennes

    Full Text Available INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia assessed virological failure (VF rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF (>1,000 copies/ml underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4% were naive and 45 (21.5% were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194 and 279 cells/mm3 (IQR: 103-455 (p<0.001, respectively. Twenty seven patients (12.9% exhibited VF (95% CI: 8.6-18.2%, including 10 naive (10/164, 6.0% and 17 pre-treated (17/45, 37.8% patients (p<0.001. Among these viremic patients, twenty-two (81.4% were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3% harbored ≥1 drug resistance mutations (DRMs whereas 3 (all belonging to pre-treated patients harbored wild-types viruses. The most frequent DRMs were M184V (86.3%, K103N (45.5% and thymidine analog mutations (TAMs (40.9%. Two (13.3% pre-treated patients harbored viruses that showed a multi-nucleos(tide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre

  1. Attention-deficit/hyperactivity disorder: the impact of methylphenidate on working memory, inhibition capacity and mental flexibility.

    Science.gov (United States)

    Bolfer, Cristiana; Pacheco, Sandra Pasquali; Tsunemi, Miriam Harumi; Carreira, Walter Souza; Casella, Beatriz Borba; Casella, Erasmo Barbante

    2017-04-01

    To compare children with attention-deficit/hyperactivity disorder (ADHD), before and after the use of methylphenidate, and a control group, using tests of working memory, inhibition capacity and mental flexibility. Neuropsychological tests were administrated to 53 boys, 9-12 years old: the WISC-III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests. The case group included 23 boys with ADHD, who were combined type, treatment-naive, and with normal intelligence without comorbidities. The control group (n = 30) were age and gender matched. After three months on methylphenidate, the ADHD children were retested. The control group was also retested after three months. Before treatment, ADHD children had lower scores than the control group on the tests (p ≤ 0.001) and after methylphenidate had fewer test errors than before (p ≤ 0.001). Methylphenidate treatment improves the working memory, inhibitory control and mental flexibility of ADHD boys.

  2. Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.

    Science.gov (United States)

    Graham, Bronwyn M; Richardson, Rick

    2010-06-01

    Fibroblast growth factor-2 (FGF2) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute FGF2, administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering FGF2 on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to FGF2 affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of FGF2 on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of FGF2 (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to FGF2 increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to FGF2 did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate FGF2 as a critical signal involved in the development of learning and memory.

  3. Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory.

    Science.gov (United States)

    Xue, Wei; Hu, Jin-feng; Yuan, Yu-he; Sun, Jian-dong; Li, Bo-yu; Zhang, Dong-ming; Li, Chuang-jun; Chen, Nai-hong

    2009-09-01

    The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd. The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF). When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus. Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.

  4. On the Relationship between Memory and Perception: Sequential Dependencies in Recognition Memory Testing

    Science.gov (United States)

    Malmberg, Kenneth J.; Annis, Jeffrey

    2012-01-01

    Many models of recognition are derived from models originally applied to perception tasks, which assume that decisions from trial to trial are independent. While the independence assumption is violated for many perception tasks, we present the results of several experiments intended to relate memory and perception by exploring sequential…

  5. Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

    Science.gov (United States)

    Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

    2013-11-01

    It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P 350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

  6. Memory dynamics under stress.

    Science.gov (United States)

    Quaedflieg, Conny W E M; Schwabe, Lars

    2018-03-01

    Stressful events have a major impact on memory. They modulate memory formation in a time-dependent manner, closely linked to the temporal profile of action of major stress mediators, in particular catecholamines and glucocorticoids. Shortly after stressor onset, rapidly acting catecholamines and fast, non-genomic glucocorticoid actions direct cognitive resources to the processing and consolidation of the ongoing threat. In parallel, control of memory is biased towards rather rigid systems, promoting habitual forms of memory allowing efficient processing under stress, at the expense of "cognitive" systems supporting memory flexibility and specificity. In this review, we discuss the implications of this shift in the balance of multiple memory systems for the dynamics of the memory trace. Specifically, stress appears to hinder the incorporation of contextual details into the memory trace, to impede the integration of new information into existing knowledge structures, to impair the flexible generalisation across past experiences, and to hamper the modification of memories in light of new information. Delayed, genomic glucocorticoid actions might reverse the control of memory, thus restoring homeostasis and "cognitive" control of memory again.

  7. Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

    Science.gov (United States)

    Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

    2003-04-01

    dose-dependent manner while non-sensitizers, such as SLS and methyl salicylate (MS), did not. To note, the metal allergens such as (NH(4))(2)[PtCl(4)], NiSO(4) and CoSO(4) augmented significantly only CD54 expression. Taking advantage of a cultured cell line, measurement of the co-stimulatory molecules, CD54 and CD86, on naive THP-1 cells following chemical exposure shows promise for the development of a simple, short-term in vitro sensitization test.

  8. Context Memory Formation Requires Activity-Dependent Protein Degradation in the Hippocampus

    Science.gov (United States)

    Cullen, Patrick K.; Ferrara, Nicole C.; Pullins, Shane E.; Helmstetter, Fred J.

    2017-01-01

    Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel…

  9. Brief, pre-learning stress reduces false memory production and enhances true memory selectively in females.

    Science.gov (United States)

    Zoladz, Phillip R; Peters, David M; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Woelke, Sarah A; Wolters, Nicholas E; Talbot, Jeffery N

    2014-04-10

    Some of the previous research on stress-memory interactions has suggested that stress increases the production of false memories. However, as accumulating work has shown that the effects of stress on learning and memory depend critically on the timing of the stressor, we hypothesized that brief stress administered immediately before learning would reduce, rather than increase, false memory production. In the present study, participants submerged their dominant hand in a bath of ice cold water (stress) or sat quietly (no stress) for 3 min. Then, participants completed a short-term memory task, the Deese-Roediger-McDermott paradigm, in which they were presented with 10 different lists of semantically related words (e.g., candy, sour, sugar) and, after each list, were tested for their memory of presented words (e.g., candy), non-presented unrelated "distractor" words (e.g., hat), and non-presented semantically related "critical lure" words (e.g., sweet). Stress, overall, significantly reduced the number of critical lures recalled (i.e., false memory) by participants. In addition, stress enhanced memory for the presented words (i.e., true memory) in female, but not male, participants. These findings reveal that stress does not unequivocally enhance false memory production and that the timing of the stressor is an important variable that could mediate such effects. Such results could have important implications for understanding the dependability of eyewitness accounts of events that are observed following stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Children's episodic memory.

    Science.gov (United States)

    Ghetti, Simona; Lee, Joshua

    2011-07-01

    Episodic memory develops during childhood and adolescence. This trajectory depends on several underlying processes. In this article, we first discuss the development of the basic binding processes (e.g., the processes by which elements are bound together to form a memory episode) and control processes (e.g., reasoning and metamemory processes) involved in episodic remembering. Then, we discuss the role of these processes in false-memory formation. In the subsequent sections, we examine the neural substrates of the development of episodic memory. Finally, we discuss atypical development of episodic memory. As we proceed through the article, we suggest potential avenues for future research. WIREs Cogni Sci 2011 2 365-373 DOI: 10.1002/wcs.114 For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  11. Long lasting attentional-context dependent visuomotor memory

    OpenAIRE

    Im, Hee Yeon; Bédard, Patrick; Song, Joo-Hyun

    2016-01-01

    Using a dual-task paradigm, we recently reported that visuomotor adaptation acquired under distraction of a secondary attention-demanding discrimination task could be remembered only when a similar distraction was present. In contrast, when tested without the distracting task, performance reverted to untrained levels (Song & Bédard, 2015). Here, we demonstrated that this newfound paradoxical benefits of consistent dual-task context lasts over one day, such that visuomotor memory retrieval is ...

  12. Does abnormal sleep impair memory consolidation in schizophrenia?

    Directory of Open Access Journals (Sweden)

    Dara S Manoach

    2009-09-01

    Full Text Available Although disturbed sleep is a prominent feature of schizophrenia, its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. Sleep disturbances are well known to impair cognition in healthy individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has generally been overlooked as a potential contributor to cognitive deficits. Amelioration of cognitive deficits is a current priority of the schizophrenia research community, but most efforts to define, characterize, and quantify cognitive deficits focus on cross-sectional measures. While this approach provides a valid snapshot of function, there is now overwhelming evidence that critical aspects of learning and memory consolidation happen offline, both over time and with sleep. Initial memory encoding is followed by a prolonged period of consolidation, integration, and reorganization, that continues over days or even years. Much of this evolution of memories is mediated by sleep. This article briefly reviews (i abnormal sleep in schizophrenia, (ii sleep-dependent memory consolidation in healthy individuals, (iii recent findings of impaired sleep-dependent memory consolidation in schizophrenia, and (iv implications of impaired sleep-dependent memory consolidation in schizophrenia. This literature suggests that abnormal sleep in schizophrenia disrupts attention and impairs sleep-dependent memory consolidation and task automation. We conclude that these sleep-dependent impairments may contribute substantially to generalized cognitive deficits in schizophrenia. Understanding this contribution may open new avenues to ameliorating cognitive dysfunction and thereby improve outcome in schizophrenia.

  13. A lower ratio of omega-6 to omega-3 fatty acids predicts better hippocampus-dependent spatial memory and cognitive status in older adults.

    Science.gov (United States)

    Andruchow, Nadia D; Konishi, Kyoko; Shatenstein, Bryna; Bohbot, Véronique D

    2017-10-01

    Evidence from several cross-sectional studies indicates that an increase in omega-6 to omega-3 fatty acids (FAs) may negatively affect cognition in old age. The hippocampus is among the first neural structures affected by age and atrophy in this brain region is associated with cognitive decline. Therefore, we hypothesized that a lower omega-6:3 FA ratio would predict better hippocampus-dependent spatial memory, and a higher general cognitive status. Fifty-two healthy older adults completed a Food Frequency Questionnaire, the Montreal Cognitive Assessment test (MoCA; a test of global cognition) and virtual navigation tasks that assess navigational strategies and spatial memory. In this cross-sectional study, a lower ratio of omega-6 to omega-3 FA intake strongly predicted more accurate hippocampus-dependent spatial memory and faster learning on our virtual navigation tasks, as well as higher cognitive status overall. These results may help elucidate why certain dietary patterns with a lower omega-6:3 FA ratio, like the Mediterranean diet, are associated with reduced risk of cognitive decline. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise.

    Science.gov (United States)

    García-Capdevila, Sílvia; Portell-Cortés, Isabel; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David

    2009-09-14

    The effect of long-term voluntary exercise (running wheel) on anxiety-like behaviour (plus maze and open field) and learning and memory processes (object recognition and two-way active avoidance) was examined on Wistar rats. Because major individual differences in running wheel behaviour were observed, the data were analysed considering the exercising animals both as a whole and grouped according to the time spent in the running wheel (low, high, and very-high running). Although some variables related to anxiety-like behaviour seem to reflect an anxiogenic compatible effect, the view of the complete set of variables could be interpreted as an enhancement of defensive and risk assessment behaviours in exercised animals, without major differences depending on the exercise level. Effects on learning and memory processes were dependent on task and level of exercise. Two-way avoidance was not affected either in the acquisition or in the retention session, while the retention of object recognition task was affected. In this latter task, an enhancement in low running subjects and impairment in high and very-high running animals were observed.

  15. Virtual Environmental Enrichment through Video Games Improves Hippocampal-Associated Memory

    Science.gov (United States)

    Clemenson, Gregory D.

    2015-01-01

    The positive effects of environmental enrichment and their neural bases have been studied extensively in the rodent (van Praag et al., 2000). For example, simply modifying an animal's living environment to promote sensory stimulation can lead to (but is not limited to) enhancements in hippocampal cognition and neuroplasticity and can alleviate hippocampal cognitive deficits associated with neurodegenerative diseases and aging. We are interested in whether these manipulations that successfully enhance cognition (or mitigate cognitive decline) have similar influences on humans. Although there are many “enriching” aspects to daily life, we are constantly adapting to new experiences and situations within our own environment on a daily basis. Here, we hypothesize that the exploration of the vast and visually stimulating virtual environments within video games is a human correlate of environmental enrichment. We show that video gamers who specifically favor complex 3D video games performed better on a demanding recognition memory task that assesses participants' ability to discriminate highly similar lure items from repeated items. In addition, after 2 weeks of training on the 3D video game Super Mario 3D World, naive video gamers showed improved mnemonic discrimination ability and improvements on a virtual water maze task. Two control conditions (passive and training in a 2D game, Angry Birds), showed no such improvements. Furthermore, individual performance in both hippocampal-associated behaviors correlated with performance in Super Mario but not Angry Birds, suggesting that how individuals explored the virtual environment may influence hippocampal behavior. SIGNIFICANCE STATEMENT The hippocampus has long been associated with episodic memory and is commonly thought to rely on neuroplasticity to adapt to the ever-changing environment. In animals, it is well understood that exposing animals to a more stimulating environment, known as environmental enrichment, can

  16. Virtual Environmental Enrichment through Video Games Improves Hippocampal-Associated Memory.

    Science.gov (United States)

    Clemenson, Gregory D; Stark, Craig E L

    2015-12-09

    The positive effects of environmental enrichment and their neural bases have been studied extensively in the rodent (van Praag et al., 2000). For example, simply modifying an animal's living environment to promote sensory stimulation can lead to (but is not limited to) enhancements in hippocampal cognition and neuroplasticity and can alleviate hippocampal cognitive deficits associated with neurodegenerative diseases and aging. We are interested in whether these manipulations that successfully enhance cognition (or mitigate cognitive decline) have similar influences on humans. Although there are many "enriching" aspects to daily life, we are constantly adapting to new experiences and situations within our own environment on a daily basis. Here, we hypothesize that the exploration of the vast and visually stimulating virtual environments within video games is a human correlate of environmental enrichment. We show that video gamers who specifically favor complex 3D video games performed better on a demanding recognition memory task that assesses participants' ability to discriminate highly similar lure items from repeated items. In addition, after 2 weeks of training on the 3D video game Super Mario 3D World, naive video gamers showed improved mnemonic discrimination ability and improvements on a virtual water maze task. Two control conditions (passive and training in a 2D game, Angry Birds), showed no such improvements. Furthermore, individual performance in both hippocampal-associated behaviors correlated with performance in Super Mario but not Angry Birds, suggesting that how individuals explored the virtual environment may influence hippocampal behavior. The hippocampus has long been associated with episodic memory and is commonly thought to rely on neuroplasticity to adapt to the ever-changing environment. In animals, it is well understood that exposing animals to a more stimulating environment, known as environmental enrichment, can stimulate neuroplasticity and

  17. Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments

    Directory of Open Access Journals (Sweden)

    Christopher Ecker

    2018-04-01

    Full Text Available Summary: T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ production in a nutrient-poor environment. Unlike naive (TN or central memory T (TCM cells, effector memory T (TEM cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments. : Ecker et al. distinguish unique metabolic and functional properties of naive and memory T cell subsets during glucose limitation. During glucose starvation, T cells begin to differentially rely on fatty acid synthesis and glutamine utilization to survive. Unexpectedly, reliance on fatty acid synthesis alters the ability to produce IFN-γ. Keywords: lipid droplets, IFN-γ, oxidative phosphorylation, reductive glutaminolysis, serum-free media, naive T cell, glycolysis, effector memory T cell, fatty acid synthesis

  18. Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus.

    Science.gov (United States)

    Chen, Xiao-Rong; Sun, Shi-Cheng; Teng, Shuai-Wen; Li, Liang; Bie, Yi-Fan; Yu, Hui; Li, Da-Li; Chen, Zhe-Yu; Wang, Yue

    2018-03-01

    Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2 +/- and Uhrf2 -/- mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.

  19. The cortical basis of true memory and false memory for motion.

    Science.gov (United States)

    Karanian, Jessica M; Slotnick, Scott D

    2014-02-01

    Behavioral evidence indicates that false memory, like true memory, can be rich in sensory detail. By contrast, there is fMRI evidence that true memory for visual information produces greater activity in earlier visual regions than false memory, which suggests true memory is associated with greater sensory detail. However, false memory in previous fMRI paradigms may have lacked sufficient sensory detail to recruit earlier visual processing regions. To investigate this possibility in the present fMRI study, we employed a paradigm that produced feature-specific false memory with a high degree of visual detail. During the encoding phase, moving or stationary abstract shapes were presented to the left or right of fixation. During the retrieval phase, shapes from encoding were presented at fixation and participants classified each item as previously "moving" or "stationary" within each visual field. Consistent with previous fMRI findings, true memory but not false memory for motion activated motion processing region MT+, while both true memory and false memory activated later cortical processing regions. In addition, false memory but not true memory for motion activated language processing regions. The present findings indicate that true memory activates earlier visual regions to a greater degree than false memory, even under conditions of detailed retrieval. Thus, the dissociation between previous behavioral findings and fMRI findings do not appear to be task dependent. Future work will be needed to assess whether the same pattern of true memory and false memory activity is observed for different sensory modalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice.

    Science.gov (United States)

    Rubio, Julio; Qiong, Wang; Liu, Xinmin; Jiang, Zhen; Dang, Haixia; Chen, Shi-Lin; Gonzales, Gustavo F

    2011-01-01

    The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX) mice and their relation with malonalehyde (MDA), acetylcholinesterase (Ache) and monoamine oxidase (MAO) brain levels. Female mice were divided into five groups: (i) naive (control), (ii) sham, (iii) OVX mice and OVX mice treated with (iv) 0.50 g kg(-1) and (v) 2.00 g kg(-1) black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23-27) and the step-down avoidance test (days 34 and 35). At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg) increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities.

  1. Deficiency in memory B cell compartment in a patient with infertility and recurrent pregnancy losses.

    Science.gov (United States)

    Sung, N; Byeon, H J; Garcia, M D Salazar; Skariah, A; Wu, L; Dambaeva, S; Beaman, K; Gilman-Sachs, A; Kwak-Kim, J

    2016-11-01

    Alterations in normal balance of B cell subsets have been reported in various rheumatic diseases. In this study, we report a woman with a history of recurrent pregnancy losses (RPL) and infertility who had low levels of memory B cells. A 35-year-old woman with a history of RPL and infertility was demonstrated to have increased peripheral blood CD19+ B cells with persistently low levels of memory B cell subsets. Prior to the frozen donor egg transfer cycle, prednisone and intravenous immunoglobulin G (IVIg) treatment was initiated and patient achieved dichorionic diamniotic twin pregnancies. During pregnancy, proportion (%) of switched memory B cells CD27+IgD- increased, while percent of total CD19+ B cells and CD27-IgD+ naive B cells were gradually decreased with a high dose IVIg treatment. She developed cervical incompetence at 20 weeks of gestation, received a Cesarean section at 32 weeks of gestation due to preterm labor, and delivered twin babies. B cell subset abnormalities may be associated with infertility, RPL and preterm labor, and further investigation is needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Context-dependent motor skill: perceptual processing in memory-based sequence production.

    Science.gov (United States)

    Ruitenberg, Marit F L; Abrahamse, Elger L; De Kleine, Elian; Verwey, Willem B

    2012-10-01

    Previous studies have shown that motor sequencing skill can benefit from the reinstatement of the learning context-even with respect to features that are formally not required for appropriate task performance. The present study explored whether such context-dependence develops when sequence execution is fully memory-based-and thus no longer assisted by stimulus-response translations. Specifically, we aimed to distinguish between preparation and execution processes. Participants performed two keying sequences in a go/no-go version of the discrete sequence production task in which the context consisted of the color in which the target keys of a particular sequence were displayed. In a subsequent test phase, these colors either were the same as during practice, were reversed for the two sequences or were novel. Results showed that, irrespective of the amount of practice, performance across all key presses in the reversed context condition was impaired relative to performance in the same and novel contexts. This suggests that the online preparation and/or execution of single key presses of the sequence is context-dependent. We propose that a cognitive processor is responsible both for these online processes and for advance sequence preparation and that combined findings from the current and previous studies build toward the notion that the cognitive processor is highly sensitive to changes in context across the various roles that it performs.

  3. Variation in Working Memory Capacity and Temporal-Contextual Retrieval from Episodic Memory

    Science.gov (United States)

    Spillers, Gregory J.; Unsworth, Nash

    2011-01-01

    Unsworth and Engle (2007) recently proposed a model of working memory capacity characterized by, among other things, the ability to conduct a strategic, cue-dependent search of long-term memory. Although this ability has been found to mediate individual variation in a number of higher order cognitive tasks, the component processes involved remain…

  4. Propagation of soil moisture memory to runoff and evapotranspiration

    Science.gov (United States)

    Orth, R.; Seneviratne, S. I.

    2012-10-01

    As a key variable of the land-climate system soil moisture is a main driver of runoff and evapotranspiration under certain conditions. Soil moisture furthermore exhibits outstanding memory (persistence) characteristics. Also for runoff many studies report distinct low frequency variations that represent a memory. Using data from over 100 near-natural catchments located across Europe we investigate in this study the connection between soil moisture memory and the respective memory of runoff and evapotranspiration on different time scales. For this purpose we use a simple water balance model in which dependencies of runoff (normalized by precipitation) and evapotranspiration (normalized by radiation) on soil moisture are fitted using runoff observations. The model therefore allows to compute memory of soil moisture, runoff and evapotranspiration on catchment scale. We find considerable memory in soil moisture and runoff in many parts of the continent, and evapotranspiration also displays some memory on a monthly time scale in some catchments. We show that the memory of runoff and evapotranspiration jointly depend on soil moisture memory and on the strength of the coupling of runoff and evapotranspiration to soil moisture. Furthermore we find that the coupling strengths of runoff and evapotranspiration to soil moisture depend on the shape of the fitted dependencies and on the variance of the meteorological forcing. To better interpret the magnitude of the respective memories across Europe we finally provide a new perspective on hydrological memory by relating it to the mean duration required to recover from anomalies exceeding a certain threshold.

  5. Remembering in Contradictory Minds: Disjunction Fallacies in Episodic Memory

    Science.gov (United States)

    Brainerd, C. J.; Reyna, V. F.; Aydin, C.

    2010-01-01

    Disjunction fallacies have been extensively studied in probability judgment. They should also occur in episodic memory, if remembering a cue's episodic state depends on how its state is described on a memory test (e.g., being described as a target vs. as a distractor). If memory is description-dependent, cues will be remembered as occupying…

  6. Memory Tests with Ambient Odours "Make Scents"

    OpenAIRE

    Nord, Marie

    2015-01-01

    An ambient odour of anise was used in a context-dependent memory study with three different memory tasks targeting both declarative and non-declarative memory functions. Declarative memory was assessed by means of two episodic memory tests; recall of a prose text and a complex figure. Priming was used to assess the non-declarative memory with word fragment completion. Memory was tested immediately and after 48 hours. The results showed a significant main effect of context (odour or not) for a...

  7. Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

    Science.gov (United States)

    Akiyama, K; Tsuchida, K; Kanzaki, A; Ujike, H; Hamamura, T; Kondo, K; Mutoh, S; Miyanagi, K; Kuroda, S; Otsuki, S

    1995-11-15

    Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

  8. Central executive involvement in children's spatial memory.

    Science.gov (United States)

    Ang, Su Yin; Lee, Kerry

    2008-11-01

    Previous research with adults found that spatial short-term and working memory tasks impose similar demands on executive resources. We administered spatial short-term and working memory tasks to 8- and 11-year-olds in three separate experiments. In Experiments 1 and 2 an executive suppression task (random number generation) was found to impair performances on a short-term memory task (Corsi blocks), a working memory task (letter rotation), and a spatial visualisation task (paper folding). In Experiment 3 an articulatory suppression task only impaired performance on the working memory task. These results suggest that short-term and working memory performances are dependent on executive resources. The degree to which the short-term memory task was dependent on executive resources was expected to be related to the amount of experience children have had with such tasks. Yet we found no significant age-related suppression effects. This was attributed to differences in employment of cognitive strategies by the older children.

  9. Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

    Science.gov (United States)

    Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

    2016-05-01

    Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.

  10. Pointing movements both impair and improve visuospatial working memory depending on serial position.

    Science.gov (United States)

    Rossi-Arnaud, Clelia; Longobardi, Emiddia; Spataro, Pietro

    2017-08-01

    Two experiments investigated the effects of pointing movements on the item and order recall of random, horizontal, and vertical arrays consisting of 6 and 7 squares (Experiment 1) or 8 and 9 squares (Experiment 2). In the encoding phase, participants either viewed the items passively (passive-view condition) or pointed towards them (pointing condition). Then, after a brief interval, they were requested to recall the locations of the studied squares in the correct order of presentation. The critical result was that, for all types of arrays, the effects of the encoding condition varied as a function of serial position: for the initial and central positions accuracy was higher in the passive-view than in the pointing condition (confirming the standard inhibitory effect of pointing movements on visuospatial working memory), whereas the reverse pattern occurred in the final positions-showing a significant advantage of the pointing condition over the passive-view condition. Findings are interpreted as showing that pointing can have two simultaneous effects on the recall of spatial locations, a positive one due to the addition of a motor code and a negative one due to the attentional requirements of hand movements, with the net impact on serial recall depending on the amount of attention resources needed for the encoding of each position. Implications for the item-order hypothesis and the perceptual-gestural account of working memory are also discussed.

  11. Sleep after Learning Aids Memory Recall

    Science.gov (United States)

    Born, Jan; Gais, Steffen; Lucas, Brian

    2006-01-01

    In recent years, the effect of sleep on memory consolidation has received considerable attention. In humans, these studies concentrated mainly on procedural types of memory, which are considered to be hippocampus-independent. Here, we show that sleep also has a persisting effect on hippocampus-dependent declarative memory. In two experiments, we…

  12. Is the Link from Working Memory to Analogy Causal? No Analogy Improvements following Working Memory Training Gains

    OpenAIRE

    Richey, J. Elizabeth; Phillips, Jeffrey S.; Schunn, Christian D.; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data [1], but less work has tested this relationship through experimental manipulation [2]. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working mem...

  13. Dependence creating properties of lipotropin C-fragment (β-endorphin): Evidence for its internal control of behavior

    NARCIS (Netherlands)

    Ree, J.M. van; Smyth, D.G.; Colpaert, F.C.

    1979-01-01

    The C-fragment of lipotropin (β-endorphin) possesses reinforcing properties, in that this peptide, like heroin, induced intraventricular self-administering behavior in drug naive rats. Only mild behavioral signs reminiscent of physical dependence were present. After injection into the nucleus raphé

  14. CD4+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity.

    Science.gov (United States)

    Marusina, Alina I; Ono, Yoko; Merleev, Alexander A; Shimoda, Michiko; Ogawa, Hiromi; Wang, Elizabeth A; Kondo, Kayo; Olney, Laura; Luxardi, Guillaume; Miyamura, Yoshinori; Yilma, Tilahun D; Villalobos, Itzel Bustos; Bergstrom, Jennifer W; Kronenberg, Daniel G; Soulika, Athena M; Adamopoulos, Iannis E; Maverakis, Emanual

    2017-02-01

    It is widely accepted that central and effector memory CD4 + T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts. CD4 + T cell repertoire analysis of highly purified T cell populations from naive animals revealed that the HEL-specific clones displayed effector and central "memory" cell surface phenotypes even prior to having encountered their cognate antigen. Furthermore, HEL-inexperienced CD4 + T cells were found to reside within the naïve, regulatory, central memory, and effector memory T cell populations at similar frequencies and the majority of the CD4 + T cells within the regulatory and memory populations were unexpanded. These findings support a new paradigm for CD4 + T cell maturation in which a specific clone can undergo a differentiation process to exhibit a "memory" or regulatory phenotype without having undergone a clonal expansion event. It also demonstrates that a foreign-specific T cell is just as likely to reside within the regulatory T cell compartment as it would the naïve compartment, arguing against the specificity of the regulatory T cell compartment being skewed towards self-reactive T cell clones. Finally, we demonstrate that the same set of foreign and autoreactive CD4 + T cell clones are repetitively generated throughout adulthood. The latter observation argues against T cell-depleting strategies or autologous stem cell transplantation as therapies for autoimmunity-as the immune system has the ability to regenerate pathogenic clones. Published by

  15. Comparative study of clozapine versus risperidone in treatment-naive, first-episode schizophrenia: A pilot study

    Directory of Open Access Journals (Sweden)

    Sukhtej Sahni

    2016-01-01

    Interpretation & conclusions: The findings of this preliminary study showed clozapine as a better choice than risperidone in terms of efficacy, tolerability and better quality of life in treatment-naive, first-episode schizophrenia. However, further studies need to be done on a larger group of patients to confirm the findings.

  16. Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    2000-01-01

    Organ-specific autoimmune diseases may be induced by infiltration of the target tissue by CD4(+) T cells with specificity for self antigen(s). As disease progresses, T cells of other specificities appear in the tissue. Traffic of naive, antigen-inexperienced T cells to target tissues has not been...

  17. Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Bottelier, Marco A; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G H; Bouziane, Cheima; Kooij, J J Sandra; de Ruiter, Michiel B; Reneman, Liesbeth

    2017-11-30

    In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0.5mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Performance evaluation of a motor-imagery-based EEG-Brain computer interface using a combined cue with heterogeneous training data in BCI-Naive subjects

    Directory of Open Access Journals (Sweden)

    Lee Youngbum

    2011-10-01

    Full Text Available Abstract Background The subjects in EEG-Brain computer interface (BCI system experience difficulties when attempting to obtain the consistent performance of the actual movement by motor imagery alone. It is necessary to find the optimal conditions and stimuli combinations that affect the performance factors of the EEG-BCI system to guarantee equipment safety and trust through the performance evaluation of using motor imagery characteristics that can be utilized in the EEG-BCI testing environment. Methods The experiment was carried out with 10 experienced subjects and 32 naive subjects on an EEG-BCI system. There were 3 experiments: The experienced homogeneous experiment, the naive homogeneous experiment and the naive heterogeneous experiment. Each experiment was compared in terms of the six audio-visual cue combinations and consisted of 50 trials. The EEG data was classified using the least square linear classifier in case of the naive subjects through the common spatial pattern filter. The accuracy was calculated using the training and test data set. The p-value of the accuracy was obtained through the statistical significance test. Results In the case in which a naive subject was trained by a heterogeneous combined cue and tested by a visual cue, the result was not only the highest accuracy (p Conclusions We propose the use of this measuring methodology of a heterogeneous combined cue for training data and a visual cue for test data by the typical EEG-BCI algorithm on the EEG-BCI system to achieve effectiveness in terms of consistence, stability, cost, time, and resources management without the need for a trial and error process.

  19. Manipulations of attention dissociate fragile visual short-term memory from visual working memory.

    Science.gov (United States)

    Vandenbroucke, Annelinde R E; Sligte, Ilja G; Lamme, Victor A F

    2011-05-01

    People often rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). Traditionally, VSTM is thought to operate on either a short time-scale with high capacity - iconic memory - or a long time scale with small capacity - visual working memory. Recent research suggests that in addition, an intermediate stage of memory in between iconic memory and visual working memory exists. This intermediate stage has a large capacity and a lifetime of several seconds, but is easily overwritten by new stimulation. We therefore termed it fragile VSTM. In previous studies, fragile VSTM has been dissociated from iconic memory by the characteristics of the memory trace. In the present study, we dissociated fragile VSTM from visual working memory by showing a differentiation in their dependency on attention. A decrease in attention during presentation of the stimulus array greatly reduced the capacity of visual working memory, while this had only a small effect on the capacity of fragile VSTM. We conclude that fragile VSTM is a separate memory store from visual working memory. Thus, a tripartite division of VSTM appears to be in place, comprising iconic memory, fragile VSTM and visual working memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats.

    Directory of Open Access Journals (Sweden)

    Marion Inostroza

    Full Text Available Cognitive impairment is a major concern in temporal lobe epilepsy (TLE. While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA from two different rat strains (Wistar and Sprague-Dawley using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se.

  1. Context-dependent repetition effects on recognition memory.

    OpenAIRE

    Opitz, B

    2010-01-01

    One widely acknowledged way to improve our memory performance is to repeatedly study the to be learned material. One aspect that has received little attention in past research regards the context sensitivity of this repetition effect, that is whether the item is repeated within the same or within different contexts. The predictions of a neuro-computational model (O'Reilly & Norman, 2002) were tested in an experiment requiring participants to study visual objects either once or three times. Cr...

  2. Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats.

    Science.gov (United States)

    Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T; Mummalaneni, Shobha; Melone, Pamela; Ren, Zuojun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S; Katsumata, Tadayoshi; DeSimone, John A; Lyall, Vijay

    2011-11-01

    Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5-40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure.

  3. HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland

    Directory of Open Access Journals (Sweden)

    Parczewski Miłosz

    2012-12-01

    Full Text Available Abstract Background HIV integrase inhibitor use is limited by low genetic barrier to resistance and possible cross-resistance among representatives of this class of antiretrovirals. The aim of this study was to analyse integrase sequence variability among antiretroviral treatment naive and experienced patients with no prior integrase inhibitor (InI exposure and investigate development of the InI drug resistance mutations following the virologic failure of the raltegravir containing regimen. Methods Sequencing of HIV-1 integrase region from plasma samples of 80 integrase treatment naive patients and serial samples from 12 patients with observed virologic failure on raltegravir containing treatment whenever plasma vireamia exceeded >50 copies/ml was performed. Drug resistance mutations were called with Stanford DB database and grouped into major and minor variants. For subtyping bootstrapped phylogenetic analysis was used; Bayesian Monte Carlo Marcov Chain (MCMC model was implemented to infer on the phylogenetic relationships between the serial sequences from patients failing on raltegravir. Results Majority of the integrase region sequences were classified as subtype B; the remaining ones being subtype D, C, G, as well as CRF01_AE , CRF02_AG and CRF13_cpx recombinants. No major integrase drug resistance mutations have been observed in InI-treatment naive patients. In 30 (38.5% cases polymorphic variation with predominance of the E157Q mutation was observed. This mutation was more common among subtype B (26 cases, 54.2% than non-B sequences (5 cases, 16.7%, p=0.00099, OR: 5.91 (95% CI:1.77-22.63]. Other variants included L68V, L74IL, T97A, E138D, V151I, R263K. Among 12 (26.1% raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R were noted in four of these cases (8.3% of the total InI-treated patients. Time to the development of drug resistance ranged

  4. Context-dependent encoding of fear and extinction memories in a large-scale network model of the basal amygdala.

    Science.gov (United States)

    Vlachos, Ioannis; Herry, Cyril; Lüthi, Andreas; Aertsen, Ad; Kumar, Arvind

    2011-03-01

    The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS)-related input from the adjacent lateral nucleus (LA) and contextual input from the hippocampus or medial prefrontal cortex (mPFC). We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA) thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories.

  5. Context-dependent encoding of fear and extinction memories in a large-scale network model of the basal amygdala.

    Directory of Open Access Journals (Sweden)

    Ioannis Vlachos

    2011-03-01

    Full Text Available The basal nucleus of the amygdala (BA is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS-related input from the adjacent lateral nucleus (LA and contextual input from the hippocampus or medial prefrontal cortex (mPFC. We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories.

  6. Negative affect impairs associative memory but not item memory.

    Science.gov (United States)

    Bisby, James A; Burgess, Neil

    2013-12-17

    The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 demonstrated that item memory was facilitated by emotional affect, whereas memory for an associated context was reduced. In Experiment 2, arousal was manipulated independently of the memoranda, by a threat of shock, whereby encoding trials occurred under conditions of threat or safety. Memory for context was equally impaired by the presence of negative affect, whether induced by threat of shock or a negative item, relative to retrieval of the context of a neutral item in safety. In Experiment 3, participants were presented with neutral and negative items as paired associates, including all combinations of neutral and negative items. The results showed both above effects: compared to a neutral item, memory for the associate of a negative item (a second item here, context in Experiments 1 and 2) is impaired, whereas retrieval of the item itself is enhanced. Our findings suggest that negative affect impairs associative memory while recognition of a negative item is enhanced. They support dual-processing models in which negative affect or stress impairs hippocampal-dependent associative memory while the storage of negative sensory/perceptual representations is spared or even strengthened.

  7. Autobiographical memory and hyperassociativity in the dreaming brain: Implications for memory consolidation in sleep

    Directory of Open Access Journals (Sweden)

    Caroline L Horton

    2015-07-01

    Full Text Available In this paper we argue that autobiographical memory activity across sleep and wake can provide insight into the nature of dreaming, and vice versa. Activated memories within the sleeping brain reflect one’s personal life history (autobiography. They can appear in largely fragmentary forms and differ from conventional manifestations of episodic memory. Autobiographical memories in dreams can be sampled from non-REM as well as REM periods, which contain fewer episodic references and become more bizarre across the night. Salient fragmented memory features are activated in sleep and re-bound with fragments not necessarily emerging from the same memory, thus de-contextualising those memories and manifesting as experiences that differ from waking conceptions. The constructive nature of autobiographical recall further encourages synthesis of these hyper-associated images into an episode via recalling and reporting dreams. We use a model of autobiographical memory to account for the activation of memories in dreams as a reflection of sleep-dependent memory consolidation processes. We focus in particular on the hyperassociative nature of autobiographical memory during sleep.

  8. IMPLEMENTASI AUGMENTED REALITY UNTUK IDENTIFIKASI LOGO DAN VIDEO SEBAGAI MEDIA INFORMASI MENGGUNAKAN METODE KLASIFIKASI NAIVE BAYESIAN

    Directory of Open Access Journals (Sweden)

    Astrid Novita Putri

    2018-04-01

    Full Text Available Pada  Universitas Semarang Fakultas Teknologi Informasi dan  Komunikasi setiap  tahun  selalu mempunyai banyak kegiatan seperti kegiatan Seminar, Workshop, Pelatihan, Festifal, dsb. Kegiatan- kegiatan  tersebut  biasanya   didokumentasikan  dalam  bentuk  foto   dan   video.   Sedangkan  untuk dokumentasi publikasi kegiatan dalam bentuk media promosi maupun media informasi belum dilakukan, sehingga masyarakat umum yang kurang familiar tidak dapat mengetahui informasi dengan kegiatan yang ada. Memanfaatkan aplikasi smartphone yang berbasis android, blackberry, dan iphone dapat menggunakan  salah  satu  teknologi  augmented  reality  3D  yang  berfungsi  untuk  mengidentifikasi informasi melalui logo Fakultas TIK dan menerapkannya pada berbagai media cetak atau elektronik. Sehingga dengan adanya perubahan cara promosi tersebut diharapkan dapat menarik minat perhatian masyarakat umum dan masyarakat umum untuk mengetahui informasi mengenai kegiatan di Universitas Semarang khususnya Fakultas Teknologi Informasi dan Komunikasi. Pada penelitian ini, akan membahas bagaimana mengklasifikasikan kegiatan-kegiatan tersebut menggunakan metode naive bayes   menjadi dua  kategori yaitu favorit atau tidak favorit. Berdasarkan data foto dan video kegiatan FTIK tahun 2017 yang telah diimplementasikan menggunakan tools Unity 3D menunjukkan bahwa penerapan Augmented Reality untuk identifikasi logo sebagai media informasi menggunakan metode klasifikasi naive bayes dapat diimplementasikan dengan baik. Diharapkan dengan adanya klasifikasi kegiatan dengan memanfaatkan teknologi  augmented  reality  yang  diimplementasikan menggunakan  tools  Unity  3D, informasi yang dihasilkan akan lebih informatif dan menarik perhatian masyarakat umum.   Kata kunci: augmented, reality, naive, bayesian, kegiatan.

  9. The Sensory Neocortex and Associative Memory.

    Science.gov (United States)

    Aschauer, Dominik; Rumpel, Simon

    2018-01-01

    Most behaviors in mammals are directly or indirectly guided by prior experience and therefore depend on the ability of our brains to form memories. The ability to form an association between an initially possibly neutral sensory stimulus and its behavioral relevance is essential for our ability to navigate in a changing environment. The formation of a memory is a complex process involving many areas of the brain. In this chapter we review classic and recent work that has shed light on the specific contribution of sensory cortical areas to the formation of associative memories. We discuss synaptic and circuit mechanisms that mediate plastic adaptations of functional properties in individual neurons as well as larger neuronal populations forming topographically organized representations. Furthermore, we describe commonly used behavioral paradigms that are used to study the mechanisms of memory formation. We focus on the auditory modality that is receiving increasing attention for the study of associative memory in rodent model systems. We argue that sensory cortical areas may play an important role for the memory-dependent categorical recognition of previously encountered sensory stimuli.

  10. On the evaluation of temperature dependence of elastic constants of martensitic phases in shape memory alloys from resonant ultrasound spectroscopy studies

    International Nuclear Information System (INIS)

    Landa, Michal; Sedlak, Petr; Sittner, Petr; Seiner, Hanus; Heller, Ludek

    2008-01-01

    Elastic constants of austenite and martensite phases in shape memory alloys reflect fundamental thermodynamic properties of these materials-i.e. important physical information can be deduced not just from the values of the constants but, mainly from their temperature and stress dependencies. As regards to the parent austenite phase, such information is available in the literature for most of the known shape memory alloys. For the martensitic phases, however, only few reliable experimental data exist, due to the experimental difficulties with the preparation of martensite single crystals as well as due to the difficulties with the ultrasonic measurement of elastic properties of strongly anisotropic media with low symmetry. In this work, the temperature dependence of all elastic constants of cubic austenite and orthorhombic 2H martensite phases in Cu-Al-Ni alloy determined by resonance ultrasound spectroscopy (RUS) is reported. Experimental and theoretical improvements of the RUS method which had to be made to perform the successful measurements on strongly anisotropic and martensitic phases are discussed

  11. Electrophysiological Repetition Effects in Persons with Mild Cognitive Impairment depend upon Working Memory Demand.

    Science.gov (United States)

    Broster, Lucas S; Jenkins, Shonna L; Holmes, Sarah D; Edwards, Matthew G; Jicha, Gregory A; Jiang, Yang

    2018-05-07

    Forms of implicit memory, including repetition effects, are preserved relative to explicit memory in clinical Alzheimer's disease. Consequently, cognitive interventions for persons with Alzheimer's disease have been developed that leverage this fact. However, despite the clinical robustness of behavioral repetition effects, altered neural mechanisms of repetition effects are studied as biomarkers of both clinical Alzheimer's disease and pre-morbid Alzheimer's changes in the brain. We hypothesized that the clinical preservation of behavioral repetition effects results in part from concurrent operation of discrete memory systems. We developed two experiments that included probes of emotional repetition effects differing in that one included an embedded working memory task. We found that neural repetition effects manifested in patients with amnestic mild cognitive impairment, the earliest form of clinical Alzheimer's disease, during emotional working memory tasks, but they did not manifest during the task that lacked the embedded working memory manipulation. Specifically, the working memory task evoked neural repetition effects in the P600 time-window, but the same neural mechanism was only minimally implicated in the task without a working memory component. We also found that group differences in behavioral repetition effects were smaller in the experiment with a working memory task. We suggest that cross-domain cognitive challenge can expose "defunct" neural capabilities of individuals with amnestic mild cognitive impairment. Copyright © 2018. Published by Elsevier Ltd.

  12. Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning.

    Science.gov (United States)

    Chia, Chester; Otto, Tim

    2013-11-01

    Mounting evidence suggests that long-lasting, protein synthesis-dependent changes in synaptic strength accompany both the initial acquisition and subsequent recall of specific memories. Within brain areas thought to be important for learning and memory, including the hippocampus, learning-related plasticity is likely mediated in part by NMDA receptor activation and experience-dependent changes in gene expression. In the present study, we examined the role of activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition, recall, and reconsolidation of memory in a trace fear conditioning paradigm. First, we show that the expression of Arc protein in ventral hippocampus (VH) is dramatically enhanced by memory recall 24h after the acquisition of trace fear conditioning, and that both memory recall and the associated recall-induced enhancement of Arc expression are blocked by pre-training administration of 2-amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect on memory recall, it significantly reduced both Arc protein expression and freezing behavior during subsequent testing sessions. Collectively, these results suggest that Arc/Arg3.1 protein plays an important functional role in both the initial acquisition of hippocampal-dependent memory and the reconsolidation of these memories after recall. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Schemas and memory consolidation.

    Science.gov (United States)

    Tse, Dorothy; Langston, Rosamund F; Kakeyama, Masaki; Bethus, Ingrid; Spooner, Patrick A; Wood, Emma R; Witter, Menno P; Morris, Richard G M

    2007-04-06

    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.

  14. Application of a naive Bayesians classifiers in assessing the supplier

    Directory of Open Access Journals (Sweden)

    Mijailović Snežana

    2017-01-01

    Full Text Available The paper considers the class of interactive knowledge based systems whose main purpose of making proposals and assisting customers in making decisions. The mathematical model provides a set of examples of learning about the delivered series of outflows from three suppliers, as well as an analysis of an illustrative example for assessing the supplier using a naive Bayesian classifier. The model was developed on the basis of the analysis of subjective probabilities, which are later revised with the help of new empirical information and Bayesian theorem on a posterior probability, i.e. combining of subjective and objective conditional probabilities in the choice of a reliable supplier.

  15. No change of dopamine transporter density in basal ganglia after risperidone treatment in drug-naive children with Tourette's disorder

    International Nuclear Information System (INIS)

    Ryu, W. K.; Ryu, Y. H.; Yoon, M. J.; Chun, K. A.; Lee, J. D.; Zee, D. Y.; Choi, T. H.

    2003-01-01

    Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the DAT densities between drug-naive children with TD and normal children investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using lodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane(I-123 IPT) single photon emission computed tomography (SPECT). I-123 IPT SPECT imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in eight drug-naive children with TD. Eight normal children also underwent SPECT imaging 2 hours after an intravenous administration of I-123 IPT and carried out both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. The drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with riperidone in children with TD was not found, although tic symptoms were significantly improved with risperidone. These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system

  16. Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway.

    Science.gov (United States)

    Zhao, Shuzhi; Li, Jun; Wang, Na; Zheng, Bingqing; Li, Tao; Gu, Qing; Xu, Xun; Zheng, Zhi

    2015-10-01

    Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid‑lowering therapeutic agent in clinical use, exerts a potential anti‑inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+‑dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR). The data demonstrated that high glucose treatment in human retinal endothelial cells (HRECs) inhibited the expression and deacetylase activity of SIRT1. The reduction of SIRT1 expression and deacetylase activity persisted following a return to normal glucose levels. Furthermore, nuclear factor‑κB expression was observed to be negatively correlated with SIRT1 expression and activity in HRECs under high glucose levels and the subsequent return to normal glucose levels. Fenofibrate treatment abrogated these changes. Knockdown of SIRT1 attenuated the effect of fenofibrate on high glucose‑induced NF‑κB expression. In addition, fenofibrate upregulated SIRT1 expression through peroxisome proliferator‑activated receptor α in high glucose‑induced metabolic memory. These findings indicate that fenofibrate is important in anti‑inflammatory processes and suppresses the cellular metabolic memory of high glucose‑induced stress via the SIRT1‑dependent signalling pathway. Thus, treatment with fenofibrate may offer a promising therapeutic strategy for halting the development of DR and other complications of diabetes.

  17. Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification

    DEFF Research Database (Denmark)

    Sambo, Francesco; Malovini, Alberto; Sandholm, Niina

    2014-01-01

    in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD. METHODS: We exploited a novel algorithm, 'Bag of Naive Bayes', whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate...

  18. CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function.

    Science.gov (United States)

    Rivino, Laura; Gruarin, Paola; Häringer, Barbara; Steinfelder, Svenja; Lozza, Laura; Steckel, Bodo; Weick, Anja; Sugliano, Elisa; Jarrossay, David; Kühl, Anja A; Loddenkemper, Christoph; Abrignani, Sergio; Sallusto, Federica; Lanzavecchia, Antonio; Geginat, Jens

    2010-03-15

    Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10-producing memory T cells. Human CD4(+)CCR6(+) memory T cells contained comparable numbers of IL-17- and IL-10-producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)-beta. In normal human spleens, the majority of CCR6(+) memory T cells were in the close vicinity of CCR6(+) myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6(+) memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6(+) T cells induced expression of IL-2, interferon-gamma, CCL20, and CD40L, and autoreactive CCR6(+) T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6(+) T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions.

  19. Reward-dependent modulation of working memory in lateral prefrontal cortex.

    Science.gov (United States)

    Kennerley, Steven W; Wallis, Jonathan D

    2009-03-11

    Although research implicates lateral prefrontal cortex (PFC) in executive control and goal-directed behavior, it remains unclear how goals influence executive processes. One possibility is that goal-relevant information, such as expected rewards, could modulate the representation of information relating to executive control, thereby ensuring the efficient allocation of cognitive resources. To investigate this, we examined how reward modulated spatial working memory. Past studies investigating spatial working memory have focused on dorsolateral PFC, but this area only weakly connects with areas processing reward. Ventrolateral PFC has better connections in this regard. Thus, we contrasted the functional properties of single neurons in ventrolateral and dorsolateral PFC as two subjects performed a task that required them to hold spatial information in working memory under different expectancies of reward for correct performance. We balanced the order of presentation of spatial and reward information so we could assess the neuronal encoding of the two pieces of information independently and conjointly. Neurons in ventrolateral PFC encoded both spatial and reward information earlier, stronger and in a more sustained manner than neurons in dorsolateral PFC. Within ventrolateral PFC, spatial selectivity was more prevalent on the inferior convexity than within the principal sulcus. Finally, when reward increased spatial selectivity, behavioral performance improved, whereas when reward decreased spatial selectivity, behavioral performance deteriorated. These results suggest that ventrolateral PFC may be a locus whereby information about expected rewards can modulate information in working memory. The pattern of results is consistent with a role for ventrolateral PFC in attentional control.

  20. Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

    Science.gov (United States)

    2016-01-01

    The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate