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Doubts about double dissociations between short- and long-term memory.

Historically, psychologists and neuroscientists have distinguished between processes supporting memory for events across retention delays of several seconds (short-term memory, STM), and those supporting memory for events across longer retention delays of minutes or more (long-term memory, LTM). Dissociations reported in some neuropsychological studies have contributed to a popular view that there must be neurally distinct memory stores that differentially support STM and LTM. In this article, we review evidence from recent studies regarding dissociations between STM and LTM. We suggest that the evidence reveals problems with claims of selective STM or LTM impairments, which in turn questions whether theories of memory need to propose neurally distinct stores for short- and long-term retention. We consider alternative ways to explain the neural mechanisms of memory across different retention intervals.

Animals↗

Differential effects of enrichment on learning and memory function in NR2B transgenic mice.

It has been known that environmental enrichment leads to better learning and memory in mice. However, the molecular mechanisms are not known. In this study, we used the 10th-12th of the NR2B transgenic (Tg) lines, in which the NMDA receptor function is enhanced via the NR2B subunit transgene in neurons of the forebrain, to test the hypothesis of the involvement of NMDA receptor function in enrichment-induced better learning and memory. Consistent with our previous results, both larger long-term potentiation (LTP) in the hippocampus and superior learning and memory were observed in naive NR2B Tg mice even after the 10th-12th generation of breeding. After enrichment, wild-type mice exhibited overall improvement in their performances in contextual and cued conditioning, fear extinctions, and novel object recognition tasks. Interestingly, the same enrichment procedures could not further increase the performance of NR2B Tg mice in contextual conditioning, cued conditioning, or fear extinction, thereby indicating that enhanced NMDA receptor function can occlude these enrichment effects. However, we found that in the novel object recognition task enriched NR2B Tg mice exhibited much longer recognition memory (up to 1 week), compared to that (up to 3 days) in naive NR2B Tg mice. Furthermore, our biochemical experiments showed that enrichment significantly increased protein levels of GluR1, NR2B, and NR2A subunits of glutamate receptors in both wild-type and NR2B Tg mice. Therefore, our results suggest an interactive nature of molecular pathways involved in both environmental and genetic NMDA receptor manipulations for enhancing learning and memory.

Animals↗

Selective muscarinic antagonists differentially affect in vivo acetylcholine release and memory performances of young and aged rats.

Brain acetylcholine release and memory performance were investigated in young (three- to six-months) and old (20- to 24-months) rats. Acetylcholine release was measured in vivo in the cortex and hippocampus of freely-moving animals, under basal conditions and in the presence of the following muscarinic antagonists: scopolamine, (+/-)-5,11-dihydro-11-[[(2-[2-[(dipropylamino) methyl]-1-piperidinyl]ethyl) amino] carbonyl]-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one (AFDX 384) and pirenzepine. The amount of acetylcholine released from the cortex and hippocampus of old rats was significantly reduced. In the presence of scopolamine and AFDX 384 but not of pirenzepine, the acetylcholine release was significantly higher in the old than the young rats, suggesting that changes in presynaptic M2/M4 muscarinic receptor function occur with ageing in the two brain regions. Cognitive capacities were evaluated using two different behavioural tasks: object recognition and passive avoidance response. Old rats were unable to discriminate between familiar and novel objects and had impaired performance in the passive avoidance test. AFDX 384 restored the performance in both tests. Furthermore, in young rats AFDX 384 reversed the impairment of both object recognition and passive avoidance response induced by scopolamine. The effect of AFDX 384 on acetylcholine release and behaviour in the old rats offers further support to a relationship between the age-related cholinergic hypofunction and cognitive impairment and indicates the blockade of presynaptic muscarinic receptors as a possible selective target for therapeutic strategies aimed at improving age-associated memory deficits.

Acetylcholine↗

Differential roles for visuospatial and verbal working memory in situation model construction.

Two experiments investigated the processing of the spatial and causal dimensions of situation models. In Experiment 1, participants read texts varying in spatial and causal demands while responding to on-line spatial and causal probes. Experiment 2 used the same design, but used texts that more tightly integrated spatial and causal information. In both experiments, spatially oriented dependent measures were generally influenced by spatial, but not causal, demands, whereas causally oriented measures were influenced by causal, but not spatial, demands. In addition, spatially oriented dependent measures were generally correlated with a measure of spatial working memory capacity, whereas causally oriented measures were correlated with a measure of verbal working memory capacity. These results indicate that spatial and causal dimensions of situation models are maintained and elaborated independently in different working memory subsystems.

Adult↗

Differential requirement for Lck during primary and memory CD8+ T cell responses.

T cell receptor (TCR) signaling mediates cell fate decisions throughout the life of a T cell. The earliest biochemical events during antigen-stimulated TCR signaling include activation of the Src-family protein tyrosine kinase, p56(Lck) (Lck), which is an integral component of the TCR signaling complex by its association with the cytoplasmic tails of CD8 or CD4. CD8 and Lck are obligatory during thymic selection of CD8+ T cells. What remain unknown are when and with what stringency Lck is required for effective TCR-mediated activation and function throughout the life of a mature CD8+ T cell. Using mice that express an inducible Lck transgene in T cells, we have investigated the temporal importance of Lck-mediated TCR signaling in antigen-specific CD8+ T cell responses during acute viral infections. We show that Lck deficiency induced in naive mice abrogated the antigen-specific activation and clonal expansion of CD8+ T cells during a primary response to acute viral infections. Moreover, the magnitude of primary CD8 T cell expansion depended on the duration of Lck-dependent TCR signaling. Quite unexpectedly, however, Lck was dispensable for enhanced functional avidity, maintenance, and reactivation of memory CD8+ T cells in vitro and in vivo. These observations suggest that the TCR signaling apparatus is rewired from an Lck-dependent state in naive CD8+ T cells to an Lck-independent state in memory CD8+ T cells. Less stringent requirements for antigen-specific TCR signaling to activate memory CD8+ T cells could, in part, account for their unique hyperreactivity to antigen, which contributes to accelerated immune control during secondary infections.

Adaptor Proteins, Signal Transducing↗

Differential age effects in semantic and episodic memory.

Results from 4 experimental tasks and 8 data sets (the 4 tasks involved either multiple sessions or different stimuli) as well as a vocabulary test conducted on the same 80 participants (40 younger and 40 older adults) are reported. The authors employed 2 semantic memory tasks (lexical decision and multiplication verification) using data from 2 sessions (for a total of 4 semantic data sets) and 2 episodic memory tasks (hybrid visual search and memory search with digits and with words as stimuli). Factor analyses using slope and intercept data from the 8 experimental data sets indicated the presence of 3 latent factors: a single intercept factor for both episodic and semantic tasks and separate slope factors for episodic and semantic tasks. A structural equation model with paths from age to 3 different 1st-order latent factors (episodic central processes, semantic central processes, and combined episodic and semantic peripheral processes) fit better than general factor models. These data are consistent with a theoretical framework in which there are age-related dissociations between peripheral and central processes across semantic and episodic memory.

Adolescent↗

Differentiating amodal familiarity from modality-specific memory processes: an ERP study.

Distinct event-related potential effects have been related to familiarity and recollection processes underlying recognition memory. Familiarity has been conceptualized as similar either to perceptual priming mechanisms supporting implicit memory or to amodal global-matching processes that should show little sensitivity to perceptual variables. The present experiment manipulated the study modality of words (auditory, visual) that were visually tested for recognition memory. The mid-frontal (300-500 ms) old/new effect often attributed to familiarity was not affected by study modality, so it appears related to an amodal familiarity process. An earlier (176-260 ms) fronto-polar old/new effect was perceptually specific in that it was observed only following visual study. The parietal old/new effect (400-800 ms), often attributed to recollection, was similar following both visual and auditory study. Temporal-spatial PCA clarified the separability of these effects.

Acoustic Stimulation↗

Differential effects of atenolol and enalapril on memory during treatment for essential hypertension.

A randomized single-blind study was designed to compare the performance on memory tests requiring recall of information relevant to everyday life of two groups of hypertensive patients. One group of 13 patients were taking a beta-adrenoceptor blocker (atenolol) and the other group of 12 patients received the angiotensin-converting enzyme inhibitor (enalapril). The results suggested that when compared with placebo the group of patients treated with enalapril showed no changes in memory function, whilst there was a mild, but consistent deficit in the group taking atenolol.

Adult↗

Cognition and vigilance: differential effects of diazepam and buspirone on memory and psychomotor performance.

Effects of a single dose of the anxiolytic buspirone (15 mg) on memory and psychomotor performance were studied in healthy volunteers and compared to those of the classic benzodiazepine anxiolytic diazepam (15 mg). The study was performed in a double-blind, placebo-controlled way. Three groups of 12 subjects were exposed to an extended test battery before and after intake of drug or placebo. Next to this, an evaluation session took place 1 week later. Immediately after intake, diazepam exerted major effects on memory, impaired psychomotor performance and decreased alertness. In particular, long-term memory had deteriorated, which was interpreted as anterograde amnesia. One week later, more items were recalled from the predrug session compared to the number of items from the postdrug session; this was interpreted as retrograde facilitation. After intake of buspirone, there were no effects of alertness and vigilance, on psychomotor performance and on memory. One week later, a small memory decrement was noticed for verbal material, which was considered as a sign of anterograde amnesia. These results indicate that effects of anxiolytics on memory can be more easily demonstrated 1 week later than immediately after drug intake and, furthermore, that the disruptive effects of diazepam outweight the small effects of buspirone. Finally, it was established that the effects of diazepam on cognition might be mediated by its effects on alertness and vigilance and that cognitive effects are not related to the anxiolytic properties of the drug.

Adult↗

Age-differences in verbal recognition memory revealed by ERP.

Seventy-four participants (aged 20-82 years) went through a continuous performance recognition memory task with multiple repetitions of words and non-words while ERPs were recorded from the scalp. The old/new ERP effect (the difference in activation to stimuli correctly recognized as old and stimuli correctly recognized as new) for words but not non-words declined with increasing age in a linear pattern, but the relationship between the old/new effect and age varied throughout the ERP time window. Differences in topography between age groups were manifested in a frontal shift in activation for older age groups. Further, the data point to differences in semantic versus non-semantic processing across the adult life span, and it is concluded that specific cognitive memory processes are differentially involved at different ages.

Adult↗

Differential subtest scores on the Rivermead Behavioural Memory Test (RBMT) in an elderly population with diagnosis of vascular or nonvascular dementia.

A retrospective analysis of subtest scores on the Rivermead Behavioural Memory Test (RBMT), a test of day-to-day memory, was completed for a clinical sample of older people. The aim was to determine whether profile and screening scores discriminated between cases classified as vascular dementia (VAD) or nonvascular dementia (NVG). Diagnosis was made on the basis of CT scan, neuropsychological assessment, and Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) criteria for dementia. The sample comprised 74 cases with a mean age of 74: 77 years (range = 60-89). A nonparametric statistical analysis indicated significant differences between the VAD and the NVG on bath the profile and screening scores and on 5 of the 12 RBMT subtests. Discriminant analysis indicated that a combination of four subtests resulted in an error rate of 3% in classifying cases as VAD or NVG in this sample. Areas for further investigation are outlined.

Journal Article↗

Differential relational encoding of categorical information in memory for action events.

Memory for action phrases is better if the actions are enacted in subject-performed tasks (SPTs) than if they are only listened to in verbal tasks (VTs). This effect is ascribed to better item-specific encoding of SPTs than of VTs. The role of interitem relational information is controversial, and the findings of clustering with categorically structured lists are inconsistent (see Engelkamp, 1998). The present study contributes to clarifying these effects by demonstrating that intentional relational encoding can be used more efficiently in VTs than in SPTs and influences the degree of clustering. If the list structure is not obvious, inducing intentional encoding by presenting the category labels prior to list presentation and asking subjects to use this preinformation increases clustering in VTs but not in SPTs. Without preinformation, clustering scores of VTs and SPTs did not differ, with preinformation, clustering of VTs was stronger than that of SPTs. The authors suggest how the inconsistent findings with regard to clustering effects can be explained.

Humans↗

IL-12 priming during in vitro antigenic stimulation changes properties of CD8 T cells and increases generation of effector and memory cells.

Antigenic and costimulatory signals trigger a developmental program by which naive CD8 T cells differentiate into effector and memory cells. However, initial cytokine signals that regulate the generation of effector and memory CD8 T cells are not well understood. In this study, we show that IL-12 priming during in vitro antigenic stimulation results in the significant increase of both primary and memory CD8 T cell population in mice after adoptive transfer of activated cells. The effect of IL-12 priming is closely associated with qualitative changes in CD8 T cells, such as reduced MHC I tetramer binding and CD69 expression, altered distribution of lipid rafts, decreased cytolytic activity, and less susceptibility to apoptosis. Furthermore, exogenous IL-12 priming improved the intrinsic survival properties of memory CD8 T cells, leading to better protective immunity and vaccine-induced memory CD8 T cell responses. However, the experiments with IL-12p40- and IL-12Rbeta1-deficient mice showed similar levels of primary and memory CD8 T cell responses compared with wild-type mice, implying that endogenous IL-12 and/or IL-12R signaling in vivo is not critical for CD8 T cell immunity. Together, our results suggest that IL-12 can serve as an important, but dispensable regulatory factor for the development of CD8 T cells, and IL-12 priming could be useful in many medical applications.

Adoptive Transfer↗

Cognitive interdependence and convergent expectations in transactive memory.

A laboratory experiment investigated the processes that underlie the development of transactive memory structures--the organizing schemes that connect knowledge held by individuals to knowledge held by others (D. M. Wegner, T. Guiliano, & P. T. Hertel, 1985). The design was a 2 x 4 factorial that controlled expectations about the partner's knowledge (similar or different from the participant's) and cognitive interdependence, the degree to which participants' outcomes depended on whether they recalled the same or different information as their partner (defined by 4 incentives). Transactive memory was most differentiated when individuals had different expertise and incentives to remember different information and most integrated when individuals had similar expertise and incentives to remember the same information. These findings may help to explain the impact of previous experience and relationships on the development of transactive memory.

Codependency, Psychological↗

Enforced expression of Bcl-2 selectively perturbs negative selection of dual reactive antibodies.

We investigated the role of apoptosis in the development of B cell memory by analyzing the (p-azophenylarsonate) Ars response in a line of A strain mice in which expression of human Bcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response in these A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Ars induced memory B cell compartment had accumulated point mutations via somatic hypermutation that increased their affinity for both Ars and the autoantigen DNA ("dual reactive" antibodies). This was in sharp contrast to normal A strain mice which displayed no dual reactive B cells in their Ars induced memory B cell compartment. These data suggested that interference with apoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice, reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibody affinity maturation nor positive selection of B cells expressing somatically mutated antibody with an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffected in A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectively alter a negative selection process that operates during memory B cell differentiation.

Animals↗

In vitro development of lymphocytes that function as progenitors for mucus-secreting lymphokine-activated killer (LAK) cells.

Two different types of cultures developed when two different interleukin 2 (IL-2) preparations were introduced into cultures of lymph node cells of nu/nu (nude) mice maintained on an embryonic fibroblast monolayer. In the first, human recombinant IL-2 (rIL-2) stimulated the generation of colonies of large cytotoxic cells identified as lymphokine-activated killer (LAK) cells that, when grown on mesenchyme fibroblastoid monolayers prepared from 16- to 18-day embryos, could be triggered to synthesize and secrete flowing mucoid material. In the second culture, crude supernatant from cultures of rat spleen cells stimulated by concanavalin A stimulated the appearance and multiplication of blast cells that, after 20 days, differentiated into lymphocytes. This population was homogeneously composed of "wandering" lymphocytes and could be kept in a stable resting form for at least 2 months without loss of viability. When exposed to rIL-2, this whole lymphocyte population underwent a transformation into blast cells that, on the fourth day, generated granules, became cytotoxic, and differentiated into granular mucus-secreting LAK cells. When low numbers of these transformed premitotic blast cells were plated on mitomycin C-treated embryonic fibroblast monolayers, one cell out of 15 to 20 generated a clone of LAK cells. The study demonstrates that both effector and "memory" arms of differentiation can be stimulated in vitro.

Animals↗

The biology of IL-12: coordinating innate and adaptive immune responses.

Cytokines play critical roles in regulating all aspects of immune responses, including lymphoid development, homeostasis, differentiation, tolerance and memory. Interleukin (IL)-12 is especially important because its expression during infection regulates innate responses and determines the type and duration of adaptive immune response. IL-12 induces interferon-gamma (IFN-gamma) production by NK, T cells, dendritic cells (DC), and macrophages. IL-12 also promotes the differentiation of naïve CD4+ T cells into T helper 1 (Th1) cells that produce IFN-gamma and aid in cell-mediated immunity. As IL-12 is induced by microbial products and regulates the development of adaptive immune cells, IL-12 plays a central role in coordinating innate and adaptive immunity. IL-12 and the recently identified cytokines, IL-23 and IL-27, define a family of related cytokines that induce IFN-gamma production and promote T cell expansion and proliferation.

Animals↗