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PubMed2006

Blocking memory reconsolidation reverses memory-associated changes in glutamate receptor expression.

It has been reported that consolidated memories can return to a labile state when reactivated and undergo a process of re-storage, termed reconsolidation, required for later recall. We investigated memory for a nonassociative learning task (habituation) and found that memory for this task also undergoes reconsolidation after recall. To investigate reconsolidation, we first demonstrated that adult Caenorhabditis elegans are capable of reliable memory 48 h after habituation training (p < 0.05). When heat shock was administered immediately after a reminder, response magnitudes of trained animals matched response levels of untrained animals: the inhibitory effects of heat shock on protein synthesis disrupted memory reconsolidation. Pharmacological blockade of non-NMDA-type glutamate receptors during reminder also eliminated 48 h retention. When expression levels of a specific glutamate receptor subunit (GLR-1) (40% homology to mammalian AMPA-type glutamate receptors) (Hart et al., 1995; Maricq et al., 1995) were measured 48 h after training, there was a significant decrease in trained compared with untrained controls. If trained worms were given a reminder followed immediately by heat shock, the effect of training on GLR-1 levels was reversed. From these studies, we conclude that both the behavioral expression of long-term memory for habituation and a cellular correlate of that memory (the alteration in expression levels of GLR-1) in C. elegans can be altered after retrieval. Furthermore, conditions that impair memory consolidation similarly disrupt memory reconsolidation, suggesting that similar mechanisms are involved.

Animals↗
PubMed2001

Twins dispute memory ownership: a new false memory phenomenon.

In three experiments, we examined a new memory phenomenon: disputed memories, in which people dispute ownership of a memory. For example, in one disputed memory each of two twins recollected being sent home from school for wearing too short a skirt, although only one of them was actually sent home. In Experiment 1, 20 sets of same-sex adult twins were asked to produce a memory for each of 45 words, and most twins spontaneously produced at least one disputed memory. In Experiment 2,20 different sets of same-sex adult twins rated disputed memories as higher in recollective experience, imagery, and emotional reliving than nondisputed memories. In Experiment 3, siblings who were close in age as well as same-sex friends were also found to have disputed memories, but less often than twins.

Adolescent↗
PubMed2004

Memory for actions: enactment and source memory.

Enacting simple action phrases enhances item memory but may not enhance other aspects of memory. The present experiment examines the effects of enactment on source memory. During the study phase, participants performed some actions (subject-performed tasks, SPTs) and observed the experimenter perform other actions (experimenter-performed tasks, EPTs). One group performed the SPTs with eyes closed, one group with eyes open (the standard condition), and one group performed SPTs facing a mirror (EPT presentation was constant across groups). As expected, item memory was better for SPTs than for EPTs. More importantly, source memory for SPTs was affected by the amount of visual feedback. As predicted by the source-monitoring framework, source memory for SPTs decreased as the amount of visual feedback increased from none (eyes closed) to moderate (standard condition) to maximal (mirror condition). In addition, SPT encoding failed to increase source memory and in one condition actually decreased source memory, relative to EPT encoding. Thus, enactment dissociated item and source memory, enhancing the former but not the latter.

Affect↗
PubMed2001

Augmentation in expression of activation-induced genes differentiates memory from naive CD4+ T cells and is a molecular mechanism for enhanced cellular response of memory CD4+ T cells.

In an attempt to understand the molecular basis for the immunological memory response, we have used cDNA microarrays to measure gene expression of human memory and naive CD4+ T cells at rest and after activation. Our analysis of 54,768 cDNA clones provides the first glimpse into gene expression patterns of memory and naive CD4+ T cells at the genome-scale and reveals several novel findings. First, memory and naive CD4+ T cells expressed similar numbers of genes at rest and after activation. Second, we have identified 14 cDNA clones that expressed higher levels of transcripts in memory cells than in naive cells. Third, we have identified 135 (130 known genes and 5 expressed sequence tags) up-regulated and 68 (42 known genes and 26 expressed sequence tags) down-regulated cDNA clones in memory CD4+ T after in vitro stimulation with anti-CD3 plus anti-CD28. Interestingly, the increase in mRNA levels of up-regulated genes was greater in memory than in naive CD4+ T cells after in vitro stimulation and was higher with anti-CD3 plus anti-CD28 than with anti-CD3 alone in both memory and naive CD4+ T cells. Finally, the changes in expression of actin and cytokine genes identified by cDNA microarrays were confirmed by Northern and protein analyses. Together, we have identified approximately 200 cDNA clones whose expression levels changed after activation and suggest that the level of expression of up-regulated genes is a molecular mechanism that differentiates the response of memory from naive CD4+ T cells.

Actins↗
PubMed2001

Heterogeneity of the memory CD4 T cell response: persisting effectors and resting memory T cells.

Defining the cellular composition of the memory T cell pool has been complicated by an inability to distinguish effector and memory T cells. We present here an activation profile assay, using anti-CD3 and antigenic stimuli, that clearly distinguishes effector and memory CD4 T cells and defines subsets of long-lived memory CD4 T cells based on CD62 ligand (CD62L) expression. The CD62L(low) memory subset functionally resembles effector cells, exhibiting hyper-responsiveness to antigenic and anti-CD3 mediated stimuli, high proliferative capacity, and rapid activation kinetics. The CD62L(high) memory subset functionally resembles resting memory cells, exhibiting hyporesponsiveness to anti-CD3 stimuli, lower proliferative capacity, and slower activation kinetics. Our results indicate that the memory CD4 T cell pool is heterogeneous, consisting of persisting effectors and resting memory T cells.

Adoptive Transfer↗
PubMed2003

Increased CD8+ T cell memory to concurrent infection at the expense of increased erosion of pre-existing memory: the paradoxical role of IL-15.

The use of cytokines during vaccination, particularly IL-15, is being considered due to the unique ability of IL-15 to enhance the proliferation of memory CD8(+) T cells. However, as homeostatic mechanisms limit excessive lymphocyte expansion, we addressed the consequences of this enhancement of T cell memory by IL-15. Infection of mice with either recombinant Mycobacterium bovis (BCG) expressing IL-15 (BCG-IL-15) or BCG and purified IL-15 resulted in an increased CD44, IL-2Rbeta expression and increased frequency of IFN-gamma-secreting CD8(+) T cells. Surprisingly, the enhancement of memory to concurrent infection by IL-15 exacerbated the attrition of pre-existing memory. Infection of mice with Listeria monocytogenes expressing OVA resulted in potent OVA(257-264)-specific CD8(+) T cell memory, and a challenge of these mice with either BCG-IL-15 or BCG and purified IL-15 resulted in an increased erosion of OVA(257-264)-specific CD8(+) T cell memory, relative to BCG. Enhancement in the erosion of OVA-specific CD8(+) T cell memory by BCG-IL-15 resulted in a consequently greater impairment in protection against a challenge with OVA-expressing tumor cells. We thus raise important questions regarding vaccinations that are aimed at maximizing T cell memory without considering the impact on pre-existing T cell memory.

Adjuvants, Immunologic↗
PubMed1975

Amplification of cell-associated immunological memory by secondary antigenic stimulus. Secondary type increase in memory.

In mice primed with a mixture of bovine serum albumin (BSA) and adjuvant (capsular polysaccharide of Klebsiella pneumoniae (CPS-K)) cell-associated immunological memory was increased secondarily after a second injection of BSA alone, whereas a primary injection of BSA alone into normal unprimed mice did not result in detectable memory. The optimum antigen doses for expression of the primary and secondary memories of adoptively transferred cells from unboosted primed donors or boosted donors in in vivo culture systems were very similar, although those observed in intact mice were very different, as reported previously. The size of the secondary memory of adoptively transferred cells from boosted donors was more than ten times greater than that of the primary memory of adoptively transferred cells from unboosted primed donors. The lag period for increase of the secondary memory was shorter than that for the primary memory. Both primary and secondary memories increased during a long period (up to 3 months) after the antigenic stimulus. From the results of this study it was concluded that cell-associated immunological memory could be amplified in a secondary fashion upon contact with a second stimulus.

Adjuvants, Immunologic↗
PubMed1982

Differential requirement for B-memory and T-memory cells in adoptive antibody formation in mouse bone marrow.

During the secondary response of mice to T-dependent antigens, antibody-producing plaque-forming cells (PFC) appear not only in peripheral lymphoid organs, but also in the bone marrow. This bone marrow antibody formation is feeble after primary immunization. The capacity of bone marrow antibody formation is dependent on the presence of antigen-specific memory cells at the moment of secondary immunization. We investigated whether hapten-primed B memory, carrier-primed T memory or both B-memory and T-memory cells are required for the adoptive PFC response in the bone marrow to T-dependent hapten-carrier conjugates. Adoptive antibody formation in the bone marrow was found after transfer of hapten-primed spleen cells, but not after transfer of carrier-primed spleen cells or virgin spleen cells. Thus, B-memory cells are obligatory for adoptive antibody formation in the bone marrow, in contrast to T-memory cells. However, T-memory cells did facilitate the bone marrow PFC response mediated by the infused B-memory cells.

Animals↗
PubMed1993

[Short-term memory functioning in schizophrenics--late components (P3) of the event-related potential recorded from schizophrenics during a memory retrieval task].

Event-related potentials were measured in 14 schizophrenic patients and age-matched 14 normal control subjects during a Sternberg's memory-scanning paradigm. The stimuli used were digits presented visually. In this paradigm each set of stimuli was presented for memorization (memory set), while varying the number of items (1, 2, 4) in each set, and following the mask stimulus, a probe item (test stimulus) appeared and was identified by the subject as belonging or not belonging to the memory set. Reaction times (RT) and performance accuracy were computed and ERPs to the test stimuli were recorded for each memory set size and response type. As P3 peaks in some schizophrenic patients were rather ambiguous, instead of using the conventional peak-picking method, P3 latency was determined from single trials using an adaptive correlating filter (ACF) technique, and P3 amplitude was measured from the latency-adjusted averages to reduce the jittering effect. For the behavioral measures, significant difference was not obtained between the groups. Though P3 latency increased and amplitude decreased as a function of memory set size for the normal controls, by contrast, neither latency nor amplitude of P3 was not influenced by memory set size for schizophrenics. Moreover, schizophrenic patients had smaller single trial P3 latency/RT correlations compared to normal controls. Applying the two memory-load dependent processes by Lewine, which are memory strength-evaluation and serial search stage, impaired ability of rehearsing or allocating attentional resource to each item, producing an increase in the strengths of their representations in the working memory, was suggested for schizophrenics. Accordingly, serial search process was hardly undertaken by schizophrenics, at least before response determination.

Adult↗
PubMed1997

[Memory complaints and memory deficits in healthy and depressed elderly individuals].

The objective of this study is: a) to determine if there is a relationship between memory complaints and depression and b) to compare actual verbal memory and memory complaints in depressed elderly patients and normal elderly individuals. The California Verbal Learning test (CVLT) was applied to measure memory performance. A questionnaire was used to evaluate complaints about memory. Depression was measured by the Beck Depression Inventory (BDI). The results show that depressive patients do not have deficits in verbal memory compared with normal aging individuals. There is an association between memory complaints and depressive symptoms. The depressive patients are significantly superior to the normal persons in memory complaints and depressive symptoms. The two groups are not different in objective measures of memory and learning tasks.

Aged↗
PubMed2000

Organization of working memory within the human prefrontal cortex: a PET study of self-ordered object working memory.

The prefrontal cortex plays a critical role in working memory, the active maintenance of information for brief periods of time for guiding future motor and cognitive processes. Two competing models have emerged to account for the growing human and non-human primate literature examining the functional neuroanatomy of working memory. One theory holds that the lateral frontal cortex plays a domain-specific role in working memory with the dorsolateral and ventrolateral cortical regions supporting working memory for spatial and non-spatial material, respectively. Alternatively, the lateral frontal cortex may play a process-specific role with the more dorsal regions becoming recruited whenever active manipulation or monitoring of information in working memory becomes necessary. Many working memory tasks do not allow for direct tests of these competing models. The present study used a novel self-ordered working memory task and positron emission tomography to identify whether dorsal or ventral lateral cortical areas are recruited during a working memory task that required extensive monitoring of non-spatial information held within working memory. We observed increased blood flow in the right dorsolateral, but not ventrolateral, prefrontal cortex. Increases in blood flow in the dorsolateral region correlated strongly with task performance. Thus, the results support the process-specific hypothesis.

Adult↗
PubMed1999

The nature of real, implanted, and fabricated memories for emotional childhood events: implications for the recovered memory debate.

A central issue in the recovered memory debate is whether it is possible to "remember" a highly emotional incident which never occurred. The present study provided an in-depth investigation of real, implanted, and fabricated (deceptive) memories for stressful childhood events. We examined whether false memories for emotional events could be implanted and, if so, whether real, implanted, and fabricated memories had distinctive features. A questionnaire was sent to participants' parents asking about six highly emotional, stressful events (e.g., serious animal attack) which the participant may have experienced in childhood. Next, across three sessions, interviewers encouraged participants (N = 77) to "recover" a memory for a false event using guided imagery and repeated retrieval attempts. In the first interview, they were asked about one real and one false event, both introduced as true according to their parents. In two subsequent interviews, they were reinterviewed about the false event. Finally, after the third inquiry about the false event, participants were asked to fabricate a memory report. Results indicated that 26% of participants "recovered" a complete memory for the false experience and another 30% recalled aspects of the false experience. Real, implanted, and fabricated memories differed on several dimensions (e.g., confidence, vividness, details, repeated details, coherence, stress). These findings have important implications for the debate over recovered and false memories.

Adolescent↗
PubMed1994

Structure of everyday memory in adults with Age-Associated Memory Impairment.

Everyday memory was tested in a group of adults manifesting Age-Associated Memory Impairment; a computerized battery of tests was constructed to simulate memory tasks of daily life. Confirmatory and other structural equation models were estimated for the entire sample of 273 Ss and for 3 age groups. A 4-factor model was found to fit the data well and was invariant across age and gender. After education had been controlled, only the General Recall factor was found to be consistently related to age in both men and women; the other 3 factors--Narrative Memory, Digit Recall, and Visual Memory--were related to age only in men. Confirmatory factor analyses of the everyday memory tests combined with several psychometric memory tests suggested that some of the latter (the Benton Visual Retention Test and Wechsler Memory Scale Hard Paired Associates) load on more than 1 factor of everyday memory, suggesting complex relationships between the 2 types of tests.

Activities of Daily Living↗
PubMed1997

Dissociations in infant memory: rethinking the development of implicit and explicit memory.

Extending the Jacksonian principle of the hierarchical development and dissolution of function to the development and dissolution of memory, researchers have concluded that implicit (procedural) memory is a primitive system, functional shortly after birth, that processes information automatically, whereas explicit (declarative) memory matures late in the 1st year and mediates the conscious recollection of a prior event. Support for a developmental hierarchy has only been inferred from the memory performance of adults with amnesia on priming and recognition-recall tests in response to manipulations of different independent variables. This article reviews evidence that very young infants exhibit memory dissociations like those exhibited by adults with normal memory on analogous memory tests in response to manipulations of the same independent variables. These data demonstrate that implicit and explicit memory follow the same developmental timetable and challenge the utility of conscious recollection as the defining characteristic of explicit memory.

Adult↗
PubMed1992

Factor analysis of the Wechsler Memory Scale and the Warrington Recognition Memory Test.

Subjects were 156 individuals referred, for psychological and neuropsychological evaluation. The Wechsler Memory Scale (WMS) including the 12h delayed condition of Russell's revision and Warrington's Recognition Memory Test (RMT) were administered as part of each evaluation. Using scores from the RMT subtests: (1) Memory for Words and (2) Memory for Faces, and scores from the WMS subtests: (3) Logical Memory, (4) Digit Span, (5) Visual Reproduction, and (6) Associate Learning flow associate pairs only), a principal components factor analysis was carried out with an orthogonal varimax rotation yielding four factors: (1) verbal learning and memory, (2) Figurai memory, (3) Recognition memory, and (4) Attention-Concentration. Results are discussed with respect to the independent, but complementary information provided by the WMS and RMT for measurement of memory functions.

Journal Article↗