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PubMed2005

Differential expression of NMDA receptor subunits and splice variants among the CA1, CA3 and dentate gyrus of the adult rat.

N-Methyl-d-aspartate (NMDA)-type glutamate receptors in the hippocampus are important mediators of both memory formation and excitotoxicity. It is thought that glutamatergic neurons of the CA1, CA3 and dentate gyrus regions of the hippocampus contribute differentially to memory formation and are differentially sensitive to excitotoxicity. The subunit and/or splice variant composition of the NMDA receptor controls many aspects of receptor function such as ligand affinity, calcium permeability and channel kinetics, as well as interactions with intracellular anchoring and regulatory proteins. Thus, one possible explanation of the differences in NMDA receptor-dependent processes, such as synaptic plasticity and excitotoxicity, among the hippocampal sub-regions is that they differ in subunit and/or splice variant expression. Here we report that the NMDA receptor subunits NR1 and NR2B, along with the four splice variant cassettes of the NR1 subunit are differentially expressed in the CA1, CA3 and dentate gyrus of the hippocampus. Expression of the AMPA receptor subunits GluR1 and GluR2 also differ. These differences may contribute to functional differences, such as with excitotoxicity and synaptic plasticity, that exist between the sub-regions of the hippocampus.

Actinin↗

PubMed1990

Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate.

Although normal numbers of CD4+ T cells are present in the human neonate, cord blood CD4+ cells are deficient in their ability to provide help for antibody production. In the present studies, we have examined the cellular basis for this functional deficit by analyzing the phenotypic properties and immunoregulatory functions of the subsets of cord blood CD4+ cells defined by anti-CD45RA mAb. In contrast to CD4+ cells from adults, greater than 90% of cord blood CD4+ cells expressed the CD45RA, CD38, and Leu-8 membrane Ag. When neonatal CD4+ cells were cultured with adult B cells and PWM or anti-CD4+ mAb, no helper function was apparent. However, when the small number of CD4+CD45RA- cells in cord blood were purified and similarly analyzed, helper activity comparable to that of adult CD4+CD45RA- cells was found. This helper function was profoundly suppressed by the presence of even small numbers of cord blood (but not adult) CD4+CD45RA+ cells. Irradiation of mitomycin C treatment of neonatal CD4+CD45RA+ cells abrogated their suppressor activity, but did not induce helper capability. However, after activation with PHA and culture in IL-2, cord blood CD4+CD45RA+ cells lost their suppressor activity and acquired the ability to provide help for B cell differentiation. This functional maturation was accompanied by their conversion to the CD4+CD45RA- phenotype. Thus, whereas cord blood CD4+CD45RA+ and CD4+CD45RA- cells share certain properties with the analogous subsets in adults, our data show that the dominant immunoregulatory function of cord blood CD4+ cells is suppression mediated by CD4+CD45RA+ (and CD38+) cells. In view of these phenotypic and functional differences between neonatal and adult CD4+CD45RA+ cells, we propose that "naive" CD4+CD45RA+ cells undergo age-related maturational changes that are unrelated to their postulated activation-dependent post-thymic differentiation into CD4+CD45RA- "memory" cells capable of helper functions.

ADP-ribosyl Cyclase↗

PubMed2006

Hemodynamic retrieval intensity in hippocampus is decreased by pre-exposure to autobiographic test items.

The purpose of this experiment was to assess the effects of probe familiarity, the consequences of having recently retrieved an autobiographic memory (AM), on subsequent recall. This was accomplished by replicating an earlier imaging experiment, using the same participants and memory probes. Subtractions between sessions showed significant pre-exposure effects (i.e., drop in BOLD signal intensity) in the prefrontal cortex, thalamus, cerebellum and other brain structures. Further, region of interest (ROI) analysis illustrated a significant decrease in neural activity in the hippocampus in both conditions. The results are discussed in terms of the pre-scan interview technique, a method applied in AM research to procure personal information. Although invaluable, we emphasize it must be used with caution as it can result in a loss of power. The widespread use of this method in AM research may explain why studies often fail to find evidence of significant responding in the hippocampus in response to memory probes. Alternatively, when activity in the hippocampus is reported, it often fails to differentiate between recent and remote memories. This point is of particular importance to the on-going consolidation debate, as it often centers on a failure to detect an effect in the hippocampus in one or both conditions.

Adult↗

PubMed1988

Effects of home nest odors on black-white preference in the developing rat: implications for developmental learning research.

Developing animals 17 and 30 days of age were tested for black-white preference in the presence of either clean shavings or soiled bedding material from the home cage. Home nest shavings markedly reduced dark preference in 17-day-old rats but had no effect on dark preference in 30-day-old rats. Because many developmental studies have used two-compartment, black and white chambers to study the effects of familiar home nest shavings on learning and memory, it may be that differential preference for black influenced the results obtained. The apparent alleviation of learning and memory deficits produced by the presence of home nest shavings may have been the result of changes in black-white preference rather than differences in learning and memory per se. Similar influences may underlie the effects of home nest stimuli on other learning tasks such as spatial alternation.

Aging↗

PubMed1987

Ideation and memory in the inkblot technique after focal cerebral lesions.

The aim was to study whether an inkblot technique can reveal differential deficits of ideation and memory related to the side and site of brain damage. Seventy-three patients with focal brain lesions and nine control patients were studied with a modified Holtzman Inkblot Technique. The results confirmed the previous Rorschach test finding that left-hemisphere-damaged patients have poor ideational productivity, whereas right-hemisphere-damaged patients have a perceptual disturbance indicated by a high number of diffuse color responses to whole blots. Furthermore, the patients with anterior lesions were inferior to the patients with posterior lesions in perceptual integration and in memory for inkblots. Deficient verbal recall was linked to left-hemisphere lesions, poor recognition and preserved verbal recall being associated with right-hemisphere lesions. The inkblot perception findings specific to the side and site of the brain lesion were unrelated to conventional intelligence test scores.

Adult↗

PubMedDate not supplied

[Memory complaints: epidemiology and diagnostic approach].

IN THE ELDERLY: Complaints of poor memory for everyday activities are common in the young as well as in the elderly. However, in the elderly, memory complaints are especially of interest on account of their frequency and the fear of being related to early Alzheimer's disease. Two types of memory complaints should distinguished. ENCODING/STORAGE DEFECTS: Memory difficulties related to early Alzheimer's disease are mainly related to a deficit in encoding and/or storage. They are restricted to the recent past and rapidly associated with temporal disorientation, limitation in everyday activities and behavioral modifications alerting the family responsible for seeking medical advice in most cases. Short examination of memory performance shows a free recall deficit which is not improved by cued recall. BENIGN DIFFICULTIES: Memory difficulties of benign type are due to a pure recall deficit: they are experienced as well for ancient as for recent past and the difficulty in recall is transient. There are no behavioral modifications or limitation in everyday activities: the disorder is purely subjective. At examination, the deficit in free recall is corrected by cueing. Benign type of memory complaints is mostly related to psychoaffective disturbances and subjects experiencing this type of memory difficulties are not at high risk for developing dementia.

Activities of Daily Living↗

PubMed2004

Double dissociations in visual and spatial short-term memory.

A visual short-term memory task was more strongly disrupted by visual than spatial interference, and a spatial memory task was simultaneously more strongly disrupted by spatial than visual interference. This double dissociation supports a fractionation of visuospatial short-term memory into separate visual and spatial components. In 6 experiments, this interpretation could be defended against alternative explanations in terms of trade-offs in resource allocation between memory tasks and interference tasks, in terms of an involvement of short-term consolidation and long-term memory, in terms of differential phonological-loop and central-executive involvement, and in terms of similarity-based interference.

Analysis of Variance↗

PubMed1988

Does "benign senescent forgetfulness" exist?

Age-related changes in memory functions are observed clinically and in the experimental psychology laboratory. The commonly used notion of "benign senescent forgetfulness" implies that such changes are part of "normal" aging and not associated with central nervous system pathology. Some investigators have advocated a diagnostic category, age-associated memory impairment, to define the memory loss that appears in healthy, elderly individuals. These concepts are problematic from a number of perspectives and need to be clarified and more rigorously investigated.

Aged↗

PubMed2004

Neurocognitive functioning and quality of life among dually diagnosed and non-substance abusing schizophrenia inpatients.

The aim of this study was to compare the domains of intellectual, memory and executive functions of persons with schizophrenia who concurrently have substance abuse disorders (the dually diagnosed) with a group of non-substance-abusing patients with schizophrenia and to ascertain if there were differences between the two groups in their perceptions of quality of life. Neuropsychological and quality of life data of 46 dually diagnosed and 43 non-substance-abusing patients with schizophrenia was analysed retrospectively. All subjects were inpatients of a state psychiatric hospital. Selected subtests of the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale-III constituted the intellectual and memory measures whilst the measures of executive functioning were the Stroop Color Word Test, the FAS version of the Controlled Oral Word Association Test, and the Trail Making Test (Trails A & B). Perceptions of quality of life were evaluated using the World Health Organization Quality of Life measure. The two groups did not differentiate on intellectual and memory domains, however, the dually diagnosed showed a significantly better facility with tasks of executive functions. In addition, the dually diagnosed expressed higher levels of satisfaction with their quality of life compared to the non-substance-abusing patients with schizophrenia. These results have implications for interventions.

Adult↗

PubMed1994

The pattern of deficit in different memory components in normal aging and dementia of Alzheimer's type.

The study explored differential patterns of deficits in different memory components as a function of dementia severity. Three groups of 58 subjects each were used: (1) highly functioning elderly who are free of neurological or psychiatric symptoms; (2) individuals with early signs of memory disturbance, whose MMSE scores were > or = 24; and (3) individuals with MMSE scores below 24, who meet criteria for DAT. Performance on the tests that assess different memory components was compared for the three groups. Results suggest pronounced change in acquisition component of memory at the onset of dementia, whereas retrieval from remote memory discriminates well between the mild and the more advanced phases of the disease. Retrieval from recent memory deteriorates more gradually. Based on these results, efficiency of different memory mechanisms was discussed.

Activities of Daily Living↗

PubMed1992

Differential effect of right and left hemispheric lesions on two memory tasks: free recall of items and recall of spatial location.

The effect of lateralized cerebral damage on free recall of items and recall of spatial location, under intentional and incidental learning conditions, was investigated. Eleven right brain-damaged (RBD) patients, 10 left brain-damaged (LBD) patients, 14 young and 11 elderly normal controls, participated in this study. The overall performance of the control groups was better than that of the patient groups. For all groups, free recall was better under intentional than under incidental learning condition. On recall of spatial location the learning condition had a differential effect on the groups. The RBD group performed better than the LBD group under intentional learning condition, while the reverse was found under incidental learning condition. The young-control group showed an advantage over the elderly-control group under intentional but not under incidental learning condition. The results are discussed in regard to different approaches to the distinction between automatic and effortful memory processes and their lateralization in the cerebral hemispheres.

Adult↗

PubMed1997

Clinical case report: memory functions after anterior communicating artery aneurysm rupture.

The case of a patient suffering from rupture of an aneurysm of the anterior communicating artery is reported. The hematoma was located in the basal forebrain, one of the anatomical regions associated with mnestic functions. Memory and other cognitive functions were studied. The patient performed well on all non-mnestic tests, but showed significant memory impairment. Anterograde memory was deficient not only in recall, but also in recognition. Performance on remote memory tests showed some differentiation. The patient remembered autobiographical material and famous faces correctly, but presented deficits on a Famous Events Test. This dissociation represents a difference in emotional content or familiarity of the material; the performance in tests using material with a higher emotional content was unremarkable. Lesions within the basal forebrain seem to deteriorate anterograde and remote memory, but performance may be inconspicuous if test material of high emotional content or familiarity is used.

Acute Disease↗

PubMed2004

Induction of memory-associated immediate early genes by nerve growth factor in rat primary cortical neurons and differentiated mouse Neuro2A cells.

Activation of several immediate early genes (IEGs) is crucial for long-term memory formation in vivo. In vitro methods of inducing these genes have not been investigated extensively. Here we present data demonstrating that application of the neurotrophin, nerve growth factor (NGF), to both rat primary neuronal cultures and differentiated mouse neuroblastoma 2A (N2A) cultures reliably induces expression of several IEGs, including Zif268, Nur77 and Arc, each of which have been linked to memory consolidation. These findings provide an in vitro model in which to test other agents that might modulate the induction of memory-associated genes.

Animals↗

PubMed2000

Dissociation of memory retrieval and search processes: an event-related fMRI study.

A cognitive task can often be subdivided into several subprocesses, which follow a specific temporal order. Here, we report an event-related functional magnetic resonance imaging (fMRI) experiment on memory search, in which the temporal onset of search in primary memory was varied relative to retrieval from secondary memory. Furthermore, previous behavioral studies demonstrated that search times in primary memory depend on the number of items in a memory set, whereas retrieval from secondary memory is a set-size independent process. We analyzed the dependency of the blood oxygenation level dependent (BOLD)-response on the temporal onset of memory search on the one hand and on memory set size on the other hand to differentiate the contribution of retrieval from secondary memory, maintenance in primary memory, item search in primary memory, and response-related processes. The timing of activation followed cue presentation bilaterally in the middle frontal gyri (Brodmann area (BA) 9,46) and the inferior parts of the precentral gyri (BA6). In all other regions of interest (ROI), supplementary motor area (SMA), posterior parietal cortex, antero-superior insula, and primary motor cortex, the onset of activation was delayed with delayed probe presentation, ruling out participation in retrieval from secondary memory. The amplitude of the BOLD-response increased with increasing memory set size in all ROI except primary motor cortex and left posterior parietal cortex. All areas with cue-associated BOLD onset, suggesting involvement in retrieval, showed prolonged BOLD activation, suggesting that they also support maintenance of the retrieved information.

Adult↗

PubMed2004

Functional differentiation within the medial temporal lobe in the rat.

The structures that comprise the medial temporal lobe (MTL) have been implicated in learning and memory. The question of primary concern in the present research was whether the group of anatomically related structures (hippocampus, subiculum, presubiculum/parasubiculum, entorhinal cortex, perirhinal/postrhinal cortex) are involved in mediating a similar memory process or whether the individual structures are differentially involved in memory processes and/or in handling various types of information. A series of five experiments were carried out that involved selectively lesioning the main MTL structures and testing each animal on radial-maze tasks and procedures that provided measures of two different memory processes (reference memory, working memory) and the utilization of two kinds of information (spatial, nonspatial). The structures were found to differ functionally, with the hippocampus and the presubiculum/parasubiculum being especially involved in processing spatial information, and the perirhinal/postrhinal cortex having a specific role in remembering information over a brief time period (working memory). Lesions of the entorhinal cortex failed to affect consistently either memory process or type of information handled, but they did result in impairments in learning the complex spatial discrimination requiring reference memory and in working memory involving nonspatial information. The pattern of behavioral impairments resulting from damage to these discrete MTL structures suggests that several of the structures make unique contributions to learning and memory.

Animals↗

PubMed2003

Selective adult age differences in an age-invariant multifactor model of declarative memory.

Confirmatory factor analysis was used to test competing models of declarative memory. Data from middle-aged participants provided support for a model comprised of 2 2nd-order (episodic and semantic memory) and 4 1st-order (recall, recognition, fluency, and knowledge) factors. Extending this model across young-old and old-old participants established support for age invariance. Tests of group differences showed an age deficit in episodic memory that was more pronounced for recall than for recognition. For semantic memory, there was an increase in knowledge from middle to young-old age and thereafter a decrease. Overall, the results support the view that episodic memory is more age sensitive than semantic memory, but they also indicate that aging has differential effects within these 2 forms of memory.

Adult↗

PubMed2004

Cortagine, a specific agonist of corticotropin-releasing factor receptor subtype 1, is anxiogenic and antidepressive in the mouse model.

Two subtypes of the corticotropin-releasing factor (CRF) receptor, CRF(1) and CRF(2), differentially modulate brain functions such as anxiety and memory. To facilitate the analysis of their differential involvement, we developed a CRF(1)-specific peptidic agonist by synthesis of chimeric peptides derived from human/rat CRF, ovine CRF (oCRF), and sauvagine (Svg). High affinity to the CRF-binding protein was prevented by introduction of glutamic acid in the binding site of the ligand. The resulting chimeric peptide, [Glu(21),Ala(40)][Svg(1-12)]x[human/rat CRF(14-30)]x[Svg(30-40)], named cortagine, was analyzed pharmacologically in cell culture by using human embryonic kidney-293 cells transfected with cDNA coding for CRF(1) or CRF(2), in autoradiographic experiments, and in behavior experiments using male C57BL/6J mice for its modulatory action on anxiety- and depression-like behaviors with the elevated plus-maze test and the forced swim test (FST), respectively. We observed that cortagine was more selective than oCRF, frequently used as CRF(1)-specific agonist, in stimulating the transfected cells to release cAMP. Cortagine's specificity was demonstrated in autoradiographic experiments by its selective binding to CRF(1) of brain sections of the mouse. After injection into the brain ventricles, it enhanced anxiety-like behavior on the elevated plus-maze at a lower dose than oCRF. Whereas at high doses, oCRF injected into the lateral intermediate septum containing predominantly CRF(2) increased anxiety-like behavior as CRF(2)-specific agonists do, cortagine did not. In contrast to its anxiogenic actions, cortagine reduced significantly the immobility time in the FST as described for antidepressive drugs. Thus, cortagine combines anxiogenic properties with antidepressive effects in the FST.

Amino Acid Sequence↗

PubMed2001

Blimp-1 over-expression abrogates IL-4- and CD40-mediated suppression of terminal B cell differentiation but arrests isotype switching.

Following stimulation, primary B cells either directly undergo terminal differentiation to IgM-secreting plasma cells or enter the memory pathway characterized by affinity maturation and isotype switching. Which of the various fates is adopted by B cells is determined by the strength and duration of the antigenic signal, the availability and quality of T cell help and additional signals derived from the germinal center milieu. High rate secretion is correlated with endogenous Blimp-1 levels and can be caused by ectopic expression of Blimp-1. Using cultures of resting primary mouse B cells stimulated in vitro in various combinations with IL-4, anti-mu F(ab')2 or anti-CD40 in the absence or presence of lipopolysaccharide, we show that IgM secretion and the expression of Blimp-1 is either not induced or even suppressed by B cell receptors (BCR) or CD40 ligation and by IL-4. Additional treatment with IL-2 and IL-5 induces Blimp-1 expression and facilitates IgM and IgG1 secretion, which can also be achieved by retroviral transduction of Blimp-1. On the other hand, the drastic increase in membrane IgG1(+) cells with time in cultures treated with IL-4 is greatly diminished in cells forced to express Blimp-1. We conclude that suppression of Blimp-1 by antigen-BCR interaction and T helper cell-dependent CD40 and IL-4 signaling are necessary to facilitate entrance into the memory pathway and to prevent terminal differentiation.

Animals↗