[Is there "hypothalamic memory" in the rat which makes possible the differential secretion of prolactin by a single stimulation of the cervix uteri?].
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Results for “memory differentiation”
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The differential localization of antibody synthesis and of immunologic memory in lymph nodes draining and not draining the site of primary immunization with hemocyanin.
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Animals↗
Differential effects of triazolam and ethanol on awareness, memory, and psychomotor performance.
Eight normal, healthy, male volunteers each received four triazolam doses (0, 2, 4, and 8 micrograms/kg) and four ethanol doses (0, 0.25, 0.5 and 1.0 g/kg) in a double-blind, double-dummy experiment in which within-subject dose sequence was determined by a balanced Latin square design. Triazolam and ethanol produced dose-related and time-related effects on subject ratings of mood and perceived drug effects and objective measures of memory and psychomotor performance. Dose-response curves for the two drugs were not parallel, and therefore, comparisons of the two drugs were based upon comparisons of the high dose of each drug. Although the two high-dose conditions generally were not different from one another, there were differences in their relative effect sizes, which were important. The high dose of each drug produced comparable degrees of impairment on two different psychomotor tasks. Triazolam, but not ethanol, produced significant impairment on two different memory tasks. The relative effects of each drug on subject ratings of mood and perceived drug effects varied across different subject-rated measures. Only ethanol significantly increased subject ratings of alcohol strength and feeling drunk. In comparison to ethanol, triazolam tended to produce less-pronounced subject ratings of drug effect magnitude, drug liking, and estimated performance impairment. However, less-pronounced subjective effects of triazolam were not universally observed on all subject ratings. Triazolam produced greater effects on several sedative symptoms and produced comparable effects on several mood factor scales.
Adult↗
A critical role for NF-kappaB transcription factors in the development of CD8+ memory-phenotype T cells.
Memory T cells are essential for generating secondary immune responses and so provide long-lived protection from pathogens. The mechanisms that regulate the differentiation and survival of memory T cells are largely unknown. Transgenic mice in which NF-kappaB activity is inhibited by the expression of a dominant-negative form of IkappaB-alpha (mIkappaB-alpha mice) have drastically diminished numbers of CD8(+) memory-phenotype cells. The development of activated mIkappaB-alpha CD8 cells into memory-phenotype CD8 cells was severely impaired after adoptive transfer to lymphopenic hosts. Our findings demonstrate a critical role for NF-kappaB transcription factors in determining the number of memory-phenotype CD8 cells.
Animals↗
Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration.
CD4+ T cells include a naive (CD4-, CD45RO-, CD29-, CD45RA+) as well as a memory subpopulation (CD4+, CD45RO+, CD29+, CD45RA-). These subpopulations represent different stages in T-cell development and function. Recently, it has been shown that inflammatory and neoplastic CD4+ T-cell infiltrates are dominated by the memory subpopulation, whereas both subpopulations are about the same size in the peripheral blood. This was thought to be the result of in situ maturation of naive into memory T cells. We analysed early positive patch-test reactions 1-2 days after antigen challenge and found that most of the CD4+ T cells that had freshly immigrated into the tissue carried the memory phenotype. Their preferential migration may be mediated by at least five adhesion molecules expressed on their cell surface. This observation has important pathogenetic implications, since memory T cells can be rapidly activated by antigens and secrete a wide variety of pro-inflammatory cytokines.
Antigens, CD↗
Hippocampal mossy fibers and swimming navigation learning in two vole species occupying different habitats.
We showed previously for mice that size differences of the infrapyramidal hippocampal mossy fiber projection (IIP-MF) correlate with spatial learning abilities. In order to clarify the role of the IIP-MF in a natural environment, we studied the bank vole (Clethrionomys glareolus), adapted to a wide range of different habitats, and the root vole (Microtus oeconomus), living in homogenous grassland habitats with small home ranges. Morphometry on Timm-stained horizontal brain sections of six C. glareolus and six M. oeconomus revealed that the size of the entire mossy fiber projection was 42% larger in C. glareolus than M. oeconomus. C. glareolus had also an IIP-MF projection about 230% larger than that of the root vole. A sample of captured animals was then transferred to the laboratory (C. glareolus, n = 23; M. oeconomus, n = 15) and underwent testing for swimming navigation according to a standardized protocol used to assess water maze learning in about 2,000 normal and transgenic mice. Both species learned faster than laboratory mice. Overall escape times showed no differences, but path length was significantly reduced in C. glareolus, which also showed superior performance in a variety of scores assessing spatial search patterns. On the other hand, M. oeconomus showed faster swimming speed, and strong thigmotaxis combined with circular swimming. M. oeconomus also scored at chance levels during the probe trial, about as poorly as mutant knockout mice considered to be deficient in spatial memory. These differences probably reflect differential styles of water maze learning rather than spatial memory deficits: C. glareolus appears to be superior in inhibiting behavior interfering with proper spatial search behavior, while M. oeconomus succeeds in escaping by using rapid circular swimming. We assume that size variations of the IIP-MF correspond to a mechanism stabilizing hippocampal processing during spatial learning or complex activities. This corresponds to the ecological lifestyle of the two species and is in line with previous observations on the role of the IIP-MF.
Animals↗
Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making.
Differentiation of uncommitted T cells into Th1 and Th2 subpopulations depends on both intracellular events controlling expression of transcription factors T-bet and GATA-3 and interactions between cells mediated by cytokines, particularly IL4 and IFNgamma. A great deal is known about the intracellular and extracellular events involved in Th1 and Th2 (Th) differentiation, but how these are integrated in T-cell populations or indeed why extracellular cytokine control is required after a decision has been made at a transcriptional level is not at all understood. We present a mathematical model of CD4+ T-cell differentiation that describes both intracellular and extracellular processes and the interactions between them. It shows how antigen stimulation in conjunction with cytokines and other extracellular signals gives rise to rapid, reversible and mutually exclusive expression of T-bet or GATA-3 due to feedback between the transcription factors and their signalling pathways. After transient signalling by APC, continued Th1 and Th2 differentiation is shown to require cytokine production by the proliferating T cells. Moreover, intercellular communication by T-cell-derived cytokines lowers the threshold of APC signals required for Th differentiation. This provides an explanation for enhanced Th differentiation by pre-existing memory T cells. The model also predicts that Th differentiation can be reversed at the single cell level before commitment by manipulating the cytokine environment. It suggests a mechanism for switching between Th1 and Th2 in the so-called irreversible state that may be developed as a novel therapeutic means of manipulating Th1 and Th2 responses.
Animals↗
Direct ex vivo analysis of human CD4(+) memory T cell activation requirements at the single clonotype level.
CD4(+) memory T cells continuously integrate signals transmitted through the TCR and costimulatory molecules, only responding when the intensity of such signals exceeds an intrinsic activation threshold. Recent data suggest that these activation thresholds can be regulated independently of TCR specificity, and that threshold tuning may constitute a major mechanism for controlling T cell effector activity. In this work we take advantage of the profound clonotypic hierarchies of the large human CD4(+) T cell response to CMV to study activation thresholds of fresh (unexpanded) memory T cells at the clonotypic level. We identified dominant responses to CMV matrix determinants mediated by single TCRB sequences within particular TCR-Vbeta families. The specific response characteristics of these single, Ag-specific, TCRB-defined clonotypes could be unequivocally determined in fresh PBMC preparations by cytokine flow cytometry with gating on the appropriate Vbeta family. These analyses revealed 1) optimal peptides capable of eliciting specific responses by themselves at doses as low as 2 pg/ml, with each log increase in dose eliciting ever-increasing frequencies of responding cells over a 4- to 5-log range; 2) significant augmentation of response frequencies at all submaximal peptide doses by CD28- and CD49d-mediated costimulation; 3) differential dose response and costimulatory characteristics for IFN-gamma and IL-2 responses; and 4) no association of activation requirements with the CD27-defined CD4(+) T cell memory differentiation pathway. Taken together these data confirm that triggering heterogeneity exists within individual CD4(+) memory T cell clonotypes in vivo and demonstrate that such single clonotypes can manifest qualitatively different functional responses depending on epitope dose and relative levels of costimulation.
Antigen-Presenting Cells↗
Transient and executive function working memory in schizophrenia.
Transient working memory requires attention and temporary storage of information, whereas executive function working memory requires additional mental manipulation of that information. Working memory impairment is common in schizophrenia patients, but only some studies have found differential impairment in executive function working memory compared to transient working memory. We measured both types of working memory using the Digit Span forward (DF) and backward (DB) tasks in a large sample of schizophrenia patients (n=267) and normal comparison subjects (n=82); in the patients, we also examined associations between performance on the Digit Span tasks and Letter-Number Sequencing (LNS), a putative executive function working memory test. Compared to healthy subjects, the schizophrenia patients showed impairment in the medium effect size range on both DF (d=-0.55) and DB (d=-0.68). DB scores predicted LNS performance, whereas DF scores did not. Worse negative symptoms were associated with worse performance on DF, DB and LNS. These results do not reflect differential executive function working memory dysfunction in schizophrenia, but appear to support transient and executive function working memory as separable constructs.
Adult↗
Induction of TNP-specific cytotoxic T lymphocyte memory in vivo in the absence of T helper cell activity.
The question of whether TH cells are required for the priming of CTL precursors (CTLp) in vivo was studied by using Txbm mice (Thymectomized, irradiated, and stem cell-reconstituted mice). In these mice, TNP-specific CTL could be induced in vitro with TNP-coupled spleen cells only if the cultures were supplemented with an IL 2-containing supernatant (ConAsup). In contrast to normal mice, TNP-specific Lyt-2-TH cells could not be induced by skin painting with trinitrochlorobenzene (TNCB) (as tested by the ability to help CTL formation from thymocyte or normal spleen precursors). These data confirm previous findings that Txbm mice possess CTLp but that their TH compartment is deficient. TNCB skin painting had, however, a clear priming effect on the CTLp population: spleen cells from TNCB-painted mice could give rise to specific CTL with a lower amount of ConAsup than spleen cells from unprimed mice. In addition to this, priming changed the CTLp so that stimulation with lightly coupled cells (0.1 mM trinitrobenzene sulfonic acid [TNBS] instead of 10 mM TNBS) became effective. These changes took place without a significant increase in the frequency of TNP-specific CTL precursors. The data obtained are consistent with the concept that at least with some antigens, CTLp proliferation (clonal expansion), which is probably caused by activated TH cells, is not required for the induction of immunologic memory in vivo.
Animals↗
Deficits for representational memory induced by septal and cortical lesions (singly and combined) in rats.
A differentiation was made between dispositional memory and representational memory. A delayed-nonmatching-to-sample task in a T-maze operationalized this distinction. Experimental brain lesions in posterior septum and in prelimbic cortex resulted in amnesia for representational memories. The amnesia ameliorated as a function of continued reinforced postoperative testing. When lesions were placed in both structures in the same animals, amnesia for representational memories also occurred, and with further testing, the amnesia ameliorated as indicated by group data. However, examination of the behavioral performance and the lesions in individual animals revealed that when both lesions were adequate, choices remained at chance levels, results suggesting permanent amnesia for representational memories. That the lesion-induced amnesia was restricted to representational memory was indicated by the fact that the rats displayed no amnesia for dispositional memories regarding what to do in the maze. They did not act like naive animals, as they should if they had forgotten the dispositional memories necessary for successful T-maze performance.
Animals↗
Defective T cell receptor-mediated signal transduction in memory CD4 T lymphocytes exposed to superantigen or anti-T cell receptor antibodies.
Lymphocytes must promote protective immune responses while still maintaining self-tolerance. Stimulation through the T cell receptor (TCR) can lead to distinct responses in naive and memory CD4 T cells. Whereas peptide antigen stimulates both naive and memory T cells, soluble anti-CD3 antibodies and bacterial superantigens stimulate only naive T cells to proliferate and secrete cytokines. Further, superantigens, like staphylococcal enterotoxin B (SEB), cause memory T cells to become anergic while soluble anti-CD3 does not. In the present report, we show that signal transduction through the TCR is impaired in memory cells exposed to either anti-CD3 or SEB. A block in signaling leads to impaired activation of the kinase ZAP-70 so that downstream signals and cell proliferation do not occur. We further show that the signaling defect is unique to each agent. In anti-CD3-treated memory T cells, the src kinase Lck is only transiently activated and does not phosphorylate and activate ZAP-70. In SEB-treated memory T cells, ZAP-70 does not interact with the TCR/CD3 complex to become accessible to Lck. Finally, we provide evidence that alternative signaling pathways are initiated in SEB-treated memory cells. Altered signaling, indicated by an elevation in activity of the src kinase Fyn, may be responsible for memory cell anergy caused by SEB. Thus, differentiation of naive T cells into memory cells is accompanied by alterations in TCR-mediated signaling that can promote heightened recall immunity or specific tolerance.
Animals↗
Adults' conceptions of everyday memory failures in others: factors that mediate the effects of target age.
This study investigated young and older adults' conceptions of memory failure in others. One hundred young and 100 older adults rated memory failures in targets of 20, 40, 60, and 80 years of age as to how likely the memory failures were due to lack of effort or lack of ability. With increasing age, targets' forgetful episodes were rated as less likely to be caused by lack of effort and more likely to be due to lack of ability. A Subject Age x Target Age interaction on ability ratings showed age to be more salient for older subjects. Memory content, type of memory, subject sex, and target sex all influenced judgment of memory failure. The results support Erber's (1989) notion of a double standard in memory-failure appraisal; they demonstrated that adults' conceptions of memory include a decremental view of memorial ability with increasing age that is differentially sensitive to subject, target, and memorial variables.
Adult↗
Snapshots from therapy: exploring operationalisations and ways of studying flashbulb memories for private events.
A total of 13 clients (10 women and 3 men, mean age 32.85 years, SD 10.50) were interviewed after finishing group therapy, and 7 were re-interviewed 4-5 months later. The clients recounted all the specific episodes they remembered from the therapy. The memories were classified as flashbulb memories or non-flashbulb memories according to two different criteria: consistency and phenomenological clarity. Clients had flashbulb memories from therapy according to both operationalisations. Flashbulb memories according to a phenomenology-based operationalisation referred to more unusual episodes and more often to episodes associated with insight than non-flashbulb memories. The consistency operationalisation did not differentiate between flashbulb and non-flashbulb memories with respect to characteristics of the remembered events. Number of remembered episodes was positively related to the subjective evaluation of the therapy.
Adult↗
Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers.
The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.
Adult↗
Age-associated memory impairment and Alzheimer's disease.
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Aged↗
Effects of different intrastimulus interval on learning of the Konorski short-term memory test in dogs.
A differentiation of instrumental responses to auditory location stimuli using the Konorski Test was investigated. Each stimulus consisted of two components separated by intrastimulus interval. The components were click series presented from four loudspeakers situated in front of the animal, on horizontal and vertical axes. Each correct response, performed to the second component of positive stimulus, was rewarded by food. Responses to negative stimuli were not reinforced. Solving the test was possible by comparing the memory trace of the first component location, with location of actually presented second component. Two groups of dogs were trained. In one group positive and negative stimuli were presented, in which intrastimulus interval lasted 1 s. In the other group, differentiation training included stimuli with intrastimulus interval lasting 3 s. Unexpectedly, the first group was unable to reach differentiation criterion, whereas the second group reached criterion without difficulty. The effect of reaching the criterion with longer and not shorter interval between stimulus components, may be specifically related to location cues as opposed to reported earlier auditory quality stimuli.
Animals↗
[Scale position probabilities in the semantic differential].
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Humans↗