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Results for “memory differentiation”

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PubMed1991

Differential effects of chronic ethanol consumptions or thiamine deficiency on spatial working memory in Balb/c mice: a behavioral and neuroanatomical study.

This study was aimed to compare the effects of either a thiamine deficiency or a chronic ethanol consumption on memory and on neuronal density within the median mammillary nucleus. Results showed that alcohol-treated (48 weeks) mice exhibited a behavioral impairment in a sequential alternation task characterized by a progressive decay of alternation rates as a function of the number of trials; such a deficit was not observed in controls and thiamine-deficient subjects. A quantitative analysis using histological sections showed an important reduction of neuronal density within the mammillary bodies following the alcohol treatment but not following thiamine deficiency.

Alcoholism↗
PubMed2006

Electrocardiographic diagnosis of myocardial infarction and ischemia during cardiac pacing.

For the diagnosis of myocardial infarction (MI) using the QRS complex, the ECG provides only a low sensitivity (25%) but high specificity (close to 100%), but one cannot determine the age of an MI from the QRS complex. Although one cannot determine with certainty the age of an MI (hours, days or even years) from a single ECG, the presence of primary ST-segment abnormalities strongly suggests the diagnosis of acute MI or severe ischemia and the possible need for emergency revascularization. For acute MI, ST elevation>or=5 mm in predominantly negative QRS complexes is the best marker with a sensitivity of 53%, and specificity of 88%. A recent investigation suggests that T wave abnormalities from ischemia can be differentiated from those caused by cardiac memory related to pacing.

Cardiac Pacing, Artificial↗
PubMed2004

Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats.

Cannabinoid receptors in the brain (CB(1)) take part in modulation of learning, and are particularly important for working and short-term memory. Here, we employed a delayed-matching-to-place (DMTP) task in the open-field water maze and examined the effects of cannabis plant extracts rich in either Delta(9)-tetrahydrocannabinol (Delta(9)-THC), or rich in cannabidiol (CBD), on spatial working and short-term memory formation in rats. Delta(9)-THC-rich extracts impaired performance in the memory trial (trial 2) of the DMTP task in a dose-dependent but delay-independent manner. Deficits appeared at doses of 2 or 5 mg/kg (i.p.) at both 30 s and 4 h delays and were similar in severity compared with synthetic Delta(9)-THC. Despite considerable amounts of Delta(9)-THC present, CBD-rich extracts had no effect on spatial working/short-term memory, even at doses of up to 50 mg/kg. When given concomitantly, CBD-rich extracts did not reverse memory deficits of the additional Delta(9)-THC-rich extract. CBD-rich extracts also did not alter Delta(9)-THC-rich extract-induced catalepsy as revealed by the bar test. It appears that spatial working/short-term memory is not sensitive to CBD-rich extracts and that potentiation and antagonism of Delta(9)-THC-induced spatial memory deficits is dependent on the ratio between CBD and Delta(9)-THC.

Animals↗
PubMed2000

Differential effects of auditory and visual signals on clock speed and temporal memory.

The effects of signal modality on duration classification in college students were studied with the duration bisection task. When auditory and visual signals were presented in the same test session and shared common anchor durations, visual signals were classified as shorter than equivalent duration auditory signals. This occurred when auditory and visual signals were presented sequentially in the same test session and when presented simultaneously but asynchronously. Presentation of a single modality signal within a test session, or both modalities but with different anchor durations did not result in classification differences. The authors posit a model in which auditory and visual signals drive an internal clock at different rates. The clock rate difference is due to an attentional effect on the mode switch and is revealed only when the memories for the short and long anchor durations consist of a mix of contributions from accumulations generated by both the fast auditory and slower visual clock rates. When this occurs auditory signals seem longer than visual signals relative to the composite memory representation.

Adult↗
PubMed2005

Differential anterior prefrontal activation during the recognition stage of a spatial working memory task.

Neuroimaging studies commonly show widespread activations in the prefrontal cortex during various forms of working memory and long-term memory tasks. However, the anterior prefrontal cortex (aPFC, Brodmann area 10) has been mainly associated with retrieval in episodic memory, and its role in working memory is less clear. We conducted an event-related functional magnetic resonance imaging study to examine brain activations in relation to recognition in a spatial delayed-recognition task. Similar to the results from previous findings, several frontal areas were strongly activated during the recognition phase of the task, including the aPFC, the lateral PFC and the anterior cingulate cortex. Although the aPFC was more active during the recognition phase, it was also active during the delay phase of the spatial working memory task. In addition, the aPFC showed greater activity in response to negative probes (non-targets) than to positive probes (targets). While our analyses focused on examining signal changes in the aPFC, other prefrontal regions showed similar effects and none of the areas were more active in response to the positive probes than to the negative probes. Our findings support the conclusion that the aPFC is involved in working memory and particularly in processes that distinguish target and non-target stimuli during recognition.

Adult↗
PubMed2002

Differential SLP-76 expression and TCR-mediated signaling in effector and memory CD4 T cells.

We present in this study novel findings on TCR-mediated signaling in naive, effector, and memory CD4 T cells that identify critical biochemical markers to distinguish these subsets. We demonstrate that relative to naive CD4 T cells, memory CD4 T cells exhibit a profound decrease in expression of the linker/adapter molecule SLP-76, while effector T cells express normal to elevated levels of SLP-76. The reduced level of SLP-76 is memory CD4 T cells is coincident with reduced phosphorylation overall, yet the residual SLP-76 couples to a subset of TCR-associated linker molecules, leading to downstream mitogen-activated protein (MAP) kinase activation. By contrast, effector CD4 T cells strongly phosphorylate SLP-76, linker for activation of T cells, and additional Grb2-coupled proteins, exhibit increased associations of SLP-76 to phosphorylated linkers, and hyperphosphorylate downstream Erk1/2 MAP kinases. Our results suggest distinct coupling of signaling intermediates to the TCR in naive, effector, and memory CD4 T cells. Whereas effector CD4 T cells amplify existing TCR signaling events accounting for rapid effector responses, memory T cells engage fewer signaling intermediates to efficiently link TCR triggering directly to downstream MAP kinase activation.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

The differential effects of post-session administration of amineptine and imipramine on memory processes in mice.

The effects of post-trial administration of amineptine, a dopaminergic antidepressant drug, were compared with those of memory-facilitating (strychnine, piracetam) or impairing drugs (phenobarbital, imipramine) on an experimental model of memory. Mice were given two sessions in open-field test and the decrease in activity at the second session (habituation) served as an index of retention. The good retention observed with a 1-day inter-session interval was impaired by post-session administration of phenobarbital (10 mg/kg i.p.) or imipramine (5.0 mg/kg i.p.). The poor retention observed with a 5-day inter-session interval was enhanced by post-session administration of strychnine (0.20 mg/kg i.p.), piracetam (1000 mg/kg i.p.) and amineptine (10 mg/kg i.p.). These findings show that different profiles of cognitive and psychomotor effects were produced by imipramine and amineptine. Amineptine, lacking sedative and anticholinergic properties which are characteristic of imipramine, interferes positively with learning and memory, in a manner similar to piracetam and strychnine.

Animals↗
PubMed2002

Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential.

During acute infection, latent and lytic Epstein-Barr virus (EBV) epitope-specific CD8(+) T cells have a CD45RO(+) CD45RA(-) phenotype. However, after resolution of the infection, a large proportion of these cells, particularly those specific for lytic viral epitopes, re-express the CD45RA molecule. The role of CD8(+) CD45RA(+) T cells in ongoing immunity to EBV and other viruses is unknown. We now demonstrate that, relative to their CD45RO(+) counterparts, the EBV-specific CD8(+) T cells that revert to CD45RA expression after acute infectious mononucleosis are not in cell cycle, have longer telomeres, and are more resistant to apoptosis partly because of increased Bcl-2 expression. However, the EBV-specific CD8(+) CD45RA(+) T cells have shorter telomeres than the total CD8(+) CD45RA(+) T-cell pool and predominantly express low levels of the CCR7 chemokine receptor, indicating that they are not naive cells. In addition, EBV-specific CD8(+) CD45RA(+) T cells can be induced to proliferate and exhibit potent cytotoxic activity against target cells loaded with specific peptide. Our results strongly suggest, therefore, that EBV-specific CD8(+) CD45RA(+) T cells represent a stabilized virus-specific memory pool and not terminally differentiated effector cells. The identification of mechanisms that enable stable virus-specific CD8(+) T cells to persist after acute infection may lead to the enhancement of antiviral immunity in immunocompromised and elderly persons.

Acute Disease↗
PubMed1993

Selective engraftment of memory CD4+ T cells with an unusual recirculation pattern and a diverse T cell receptor-V beta repertoire into scid mice.

Young (H-2d, Ld+) severe combined immunodeficiency (scid) mice were injected intravenously with 10(5) CD4+CD8- T cells purified from spleen, thymus or lymph nodes (LN) of dm2 (H-2d, Ld-) donor mice. In the immunodeficient recipients, the lymphoid compartment in the splenic white pulp was repopulated with donor-type T cells and cellularity in the red pulp was increased. In addition, donor-type CD4+ T cells repopulated the peritoneal cavity, mesenteric LN and the lamina propria of the small intestine of scid mice, but were undetectable in thymus and peripheral (inguinal, axillary) LN. Histological examination of repopulated mesenteric LN showed expanded subcapsular sinuses, repopulated cortical areas, but poorly developed high endothelial venules (HEV) indicating deficient blood-LN lymphocyte recirculation. The engrafted CD4+ T cell population had the surface phenotype of memory T cells (CD44/Pgp-1high CD45RB(low) and expressed the Peyer's patch HEV-specific homing receptor CD49d (LPAM-1), but not the LN HEV-specific homing receptor LECAM-1. The CD4+ T cell population in spleen and mesenteric LN of transplanted scid mice displayed a diverse T cell receptor-V beta repertoire. Transfer of titrated numbers (10(3), 10(4), 10(5) cells per mouse) of CD4+ T cells into scid mice established donor-type T cell populations with this unusual homing pattern in all recipients. Repeated serial transfers of dm2 CD4+ T cells through young scid mice revealed an extensive in vivo expansion potential of transferred cells for > 18 months. The experimental system described represents an in vivo model to study the functional competence and the differentiation potential of a murine memory CD4+ T cell subset.

Animals↗
PubMed1993

Control of lymphocyte recirculation in man. I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition.

Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation through secondary lymphoid tissues, whereas memory/effector populations are composed of distinct subsets with differential, often tissue-selective migratory capability. In keeping with these observations, CD45RAhigh/ROlow "virgin" T cells in human peripheral blood uniformly express the peripheral lymph node homing receptor (HR) L-selectin, whereas among the CD45RAlow/ROhigh "memory/effector" subset, the expression of this HR is bimodal. To investigate the mechanisms responsible for the generation of memory/effector T cell subsets with differential homing potential, we developed a multiparameter flow cytometric technique that defines a common pathway of post-thymic T cell differentiation in secondary lymphoid tissues. Our analyses indicate that the virgin to memory T cell transition is characterized by a stepwise, unidirectional progression through distinct CD45RA+/RO+ intermediates that allow the in vivo discrimination of early, middle, and late transitional T cells. In normal peripheral blood, few T cells with a transitional phenotype are identified, but in secondary lymphoid tissues, 2 to 10% of T cells have this phenotype, including those CD45RA+ T cells that 1) are morphologically blasts, 2) are in S or G2/M phase of the cell cycle, or 3) express activation Ag. General adhesion molecules (LFA-1, LFA-3, ICAM-1) are uniformly up-regulated concordant with changes in T cell expression of CD45RA/RO in all tissues examined. Early in the transition, L-selectin is also uniformly up-regulated, but in subsequent stages, T cell expression of this HR is preferentially down-regulated in mucosal lymphoid tissues, and retained in peripheral lymph node. Differential regulation of L-selectin can also be demonstrated in vitro by the activation of virgin T cells in the presence of specific cytokines--IL-2 induces L-selectin down-regulation, whereas IL-6 and particularly TGF-beta 1 promote L-selectin up-regulation. Taken together, these findings support the hypothesis that local microenvironments within particular secondary lymphoid tissues influence HR expression at the time of CD45RA/RO conversion, and thereby contribute to the formation of CD45RAlow/ROhigh memory/effector T cell populations with tissue-selective homing behavior.

Adult↗
PubMed2004

The dissociation paradigm and its discontents: how can unconscious perception or memory be inferred?

Erdelyi does us all a great service by his customarily incisive discussion of the various ways in which our field tends to neglect, confuse, and misunderstand numerous critical issues in attempting to differentiate conscious from unconscious perception and memory. Although no single commentary could hope to comprehensively assess these issues, I will address Erdelyi's three main points: (1) How (and if) the dissociation paradigm can be used to validly infer unconscious perception; (2) The implications of below-chance effects; and (3) The role of time. I suggest that (a) significant progress on construct validity issues is possible; (b) below-chance effects are part of a more general bidirectional phenomenon, very likely unconscious, and do not threaten absolute subliminality; and (c) practice/learning effects pose potential difficulties for time-based dissociation paradigms.

Humans↗
PubMed2004

Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging.

The hippocampal formation contains a distinct population of neurons organized into separate anatomical subregions. Each hippocampal subregion expresses a unique molecular profile accounting for their differential vulnerability to mechanisms of memory dysfunction. Nevertheless, it remains unclear which hippocampal subregion is most sensitive to the effects of advancing age. Here we investigate this question by using separate imaging techniques, each assessing different correlates of neuronal function. First, we used MRI to map cerebral blood volume, an established correlate of basal metabolism, in the hippocampal subregions of young and old rhesus monkeys. Second, we used in situ hybridization to map Arc expression in the hippocampal subregions of young and old rats. Arc is an immediate early gene that is activated in a behavior-dependent manner and is correlated with spike activity. Results show that the dentate gyrus is the hippocampal subregion most sensitive to the effects of advancing age, which together with prior studies establishes a cross-species consensus. This pattern isolates the locus of age-related hippocampal dysfunction and differentiates normal aging from Alzheimer's disease.

Aging↗
PubMed2006

DNA methylation by DNA methyltransferase 1 is critical for effector CD8 T cell expansion.

Transcriptional silencing mediated by DNA methylation is a critical component of epigenetic regulation during early embryonic development in animals. However, the requirement for DNA methylation during activation and differentiation of mature CD8+ T cells into effector and memory cells is not clear. Using cre-mediated deletion of DNA methyltransferase 1 (Dnmt1) at the time of CD8+ T cell activation, we investigated the obligation for maintaining patterns of DNA methylation during the generation of Ag-specific effector and memory CD8+ T cells in response to acute viral infection of mice with lymphocytic choriomeningitis virus. Dnmt1-/- CD8+ T cells failed to undergo the massive CD8+ T cell expansion characteristic of lymphocytic choriomeningitis virus infection, leading to >80% reductions in Ag-specific effector CD8+ T cells at the height of the response. Despite this, Dnmt1-/- CD8+ T cells efficiently controlled the viral infection. Interestingly, the number of Ag-specific Dnmt1-/- memory CD8+ T cells was moderately reduced compared with the reductions seen at day 8 postinfection. Our data suggest that ablation of Dnmt1 and subsequent DNA methylation affect the finite proliferative potential of Ag-specific CD8+ T cells with moderate effects on their differentiation to effector and memory CD8+ T cells.

Animals↗
PubMed1989

Effects of anterior or dorsomedial thalamic ibotenic lesions on learning and memory in rats.

Sprague-Dawley rats were used to study the effects of ibotenic acid lesions of the anterior (A.Th.) and the dorsomedial (MD) thalamic nuclei on learning and memory. Memory was assessed by employing a temporal alternation task in a straight alley with varying intertrial intervals. In addition, spatial orientation and response flexibility were evaluated on a radial maze and on a spatial reversal task (SSDR). The results indicated that MD rats required more trials to learn the temporal alternation task and exhibited impaired performance compared to A.Th. and control groups at the shortest delay (15 s). In contrast, compared to the control group, A.Th. subjects which required less trials to master the task and exhibited normal performance at the 15-s delay were impaired when the intertrial interval was increased to 45 s. Whatever the lesion, no impairments were found in the SSDR or the radial maze while only MD lesions were found to result in a night hyperactivity associated with greater food and water consumptions. These findings indicate that A.Th. and MD are differentially involved in learning and memory processes. It is suggested that the MD is mostly involved in registering new information while the A.Th. plays a role in the maintenance of information over time.

Animals↗
PubMed2004

Phenotypic heterogeneity of antigen-specific CD4 T cells under different conditions of antigen persistence and antigen load.

The factors responsible for the phenotypic heterogeneity of memory CD4 T cells are unclear. In the present study, we have identified a third population of memory CD4 T cells characterized as CD45RA(+)CCR7(-) that, based on its replication history and the homeostatic proliferative capacity, was at an advanced stage of differentiation. Three different phenotypic patterns of memory CD4 T cell responses were delineated under different conditions of antigen (Ag) persistence and load using CD45RA and CCR7 as markers of memory T cells. Mono-phenotypic CD45RA(-)CCR7(+) or CD45RA(-)CCR7(-) CD4 T cell responses were associated with conditions of Ag clearance (tetanus toxoid-specific CD4 T cell response) or Ag persistence and high load (chronic HIV-1 and primary CMV infections), respectively. Multi-phenotypic CD45RA(-)CCR7(+), CD45RA(-)CCR7(-) and CD45RA(+)CCR7(-) CD4 T cell responses were associated with protracted Ag exposure and low load (chronic CMV, EBV and HSV infections and HIV-1 infection in long-term nonprogressors). The mono-phenotypic CD45RA(-)CCR7(+) response was typical of central memory (T(CM)) IL-2-secreting CD4 T cells, the mono-phenotypic CD45RA(-)CCR7(-) response of effector memory (T(EM)) IFN-gamma-secreting CD4 T cells and the multi-phenotypic response of both IL-2- and IFN-gamma-secreting cells. The present results indicate that the heterogeneity of different Ag-specific CD4 T cell responses is regulated by Ag exposure and Ag load.

Antigens↗
PubMed1999

Assessing the replicative history of human T cells.

Upon encountering antigen, T cells clonally expand and differentiate into effector cells that directly or indirectly eliminate antigen-bearing pathogens. When renewed contact with the same pathogen occurs the immune response is mounted in a faster and more accurate way, a process that is referred to as immunological memory. The basis for T-cell memory is at least partially provided by an enhanced precursor frequency of antigen-specific T cells, and an increased responsiveness of primed T cells to activation signals. In contrast to B cells, which acquire mutations in the immunoglobulin genes after antigenic challenge, somatic markers are lacking that distinguish unprimed (or naive) from primed (encompassing memory and effector) T cells. Instead, differential expression of cell surface molecules on subsets of T cells and measures for replicative history can be used to obtain insight into the antigen-driven development of the T-cell compartment. Apart from fundamental issues addressing lineage relationships between naive, memory and effector T cells and the cellular basis for long-term T-cell memory, these types of studies have proved to be valuable in understanding T-cell reconstitution in situations of severe T-cell depletion, i.e., after chemotherapy, treatment with depleting CD4 monoclonal antibodies or during HIV infection.

Age Factors↗