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PubMed2006

Dynamics of memory representations in networks with novelty-facilitated synaptic plasticity.

The ability to associate some stimuli while differentiating between others is an essential characteristic of biological memory. Theoretical models identify memories as attractors of neural network activity, with learning based on Hebb-like synaptic modifications. Our analysis shows that when network inputs are correlated, this mechanism results in overassociations, even up to several memories "merging" into one. To counteract this tendency, we introduce a learning mechanism that involves novelty-facilitated modifications, accentuating synaptic changes proportionally to the difference between network input and stored memories. This mechanism introduces a dependency of synaptic modifications on previously acquired memories, enabling a wide spectrum of memory associations, ranging from absolute discrimination to complete merging. The model predicts that memory representations should be sensitive to learning order, consistent with recent psychophysical studies of face recognition and electrophysiological experiments on hippocampal place cells. The proposed mechanism is compatible with a recent biological model of novelty-facilitated learning in hippocampal circuitry.

Animals↗
PubMed2003

Differentiation of naive CD4+ T cells towards T helper 2 cells is not impaired in rheumatoid arthritis patients.

An impaired differentiation of naive CD4+ T cells towards Th2 cells may contribute to the chronic tissue-destructive T-cell activity in rheumatoid arthritis (RA). The differentiation of naive CD4+ T cells into memory Th2 cells by IL-7 in comparison with that by IL-4 was studied in RA patients and in healthy controls. Naive CD4+ T cells from peripheral blood were differentiated by CD3/CD28 costimulation in the absence of or in the presence of IL-7 and/or IL-4. The production of IFN-gamma and IL-4 was measured by ELISA and by single-cell FACS analysis to indicate Th1 and Th2 cell activity. CD3/CD28 costimulation and IL-7 were early inducers of IL-4 production, but primarily stimulated IFN-gamma production. In contrast, in short-term cultures exogenously added IL-4 did not prime for IL-4 production but suppressed IL-7-induced IFN-gamma production. Upon long-term stimulation of naive CD4+ T cells, IFN-gamma production was differentially regulated by IL-7 and IL-4, but IL-4 production was increased by both IL-7 and IL-4. IL-7 and IL-4 additively induced polarization towards a Th2 phenotype. This susceptibility of naive CD4+ T cells to become Th2 cells upon culture with IL-7 and IL-4 was increased in RA patients compared with that in healthy controls. These findings demonstrate that, in RA patients, differentiation of naive CD4+ T cells towards a Th2 phenotype by CD3/CD28 costimulation, IL-7 and IL-4 is not impaired. The perpetuation of arthritogenic T-cell activity in RA therefore seems not to be the result of intrinsic defects of naive CD4+ T cells to develop towards suppressive memory Th2 cells.

Adult↗
PubMed1999

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is differentially expressed during human B cell differentiation and inhibits B cell receptor-mediated signaling.

Leukocyte-associated Ig-like receptor-1 (LAIR-1) belongs to the growing family of immunoreceptor tyrosine-based inhibitory motif-bearing receptors and is expressed on the majority of peripheral mononuclear cells, including NK cells, T cells, B cells, monocytes, and dendritic cells. In this study, we investigated the distribution and the capacity of LAIR-1 to function as an inhibitory receptor on human B cells. LAIR-1 is expressed from early on during B cell differentiation, but is absent on approximately half of the memory B cells, and all germinal center B cells, plasmablasts, and terminally differentiated plasma cells. In vitro stimulation of naive B cells via the B cell receptor (BCR) or CD40, triggering proliferation and differentiation into Ig-producing plasma cells, is accompanied by loss of LAIR-1 expression. We previously reported that LAIR-1 can function as an inhibitory receptor on NK cells and T cells. Here, we demonstrate that it can also function as a negative regulator of BCR-mediated signaling, since simultaneous cross-linking of LAIR-1 and the BCR reduces the increase of intracellular Ca(2+) evoked by BCR ligation. Taken together, this suggests that the inhibitory mechanism of LAIR-1 is functional in multiple components of the hematopoietic system.

Adult↗
PubMed2006

Irradiation as an experimental tool in studies of adult neurogenesis.

"Loss of function" experiments have been the mainstay approach in studies seeking to determine functional roles of various brain regions in learning and memory. The hippocampal formation consists of several distinct regions that are thought to play different, yet interrelated, roles in the memory processes. Ionizing radiation offers a selective and highly flexible, relatively uninvasive method to further advance such studies. Focused applications of the radiation beam to the head under general anesthesia can selectively reduce ongoing adult neurogenesis in the dentate gyrus without causing any detectable damage to mature neurons. Further refinements of the methodology should offer many opportunities to extend our present knowledge of how and when adult neurogenesis plays a role in learning and memory.

Animals↗
PubMed2002

Dissociating sentential prosody from sentence processing: activation interacts with task demands.

Sentence processing was contrasted with processing of syntactic prosody under two task conditions in order to examine the representation of these components of language and their interaction with working memory load. Twelve adults received fMDI scans while they listened to low-pass filtered and unfiltered sentences either passively, or during tasks that required subjects to remember and recognize information contained in the stimuli. Results indicated that temporal activation for prosodic stimuli differed compared to activation for sentence stimuli only during passive listening tasks. The inclusion of memory demands was associated with frontal activation, which was differentially lateralized for sentence and prosodic stimuli. The results demonstrate differential brain activation for prosodic vs sentential stimuli which interacts with the memory demands placed on the subjects.

Adult↗
PubMed1981

Effects of anisomycin on retention of the passive-avoidance habit as a function of age.

Three age groups of male Swiss albino CD-1 mice (2-3 mo, 6-7 mo, and 14-15 mo) were treated with a 120 mg/kg dose of the protein synthesis inhibitor anisomycin or with an equal volume of saline at various times before and after training (20 min pretraining, 0, 10, 30, or 180 min posttraining) in a shock motivated passive-avoidance task. Young (2-3 mo) and intermediate-aged (6-7 mo) mice treated with anisomycin before or immediately after training demonstrated impaired retention at a 7 day test, but retention was normal for mice injected 10, 30 or 180 min posttraining. The older mice (14-15 mo) showed similar results, with one exception: those older mice injected with anisomycin 10 min posttraining were significantly impaired in retention as compared to older saline controls and to identically treated young or intermediate-age mice. The prolonged gradient of retrograde amnesia demonstrated by older mice could not be accounted for by impaired acquisition, impaired short-term memory, altered spontaneous locomotor activity, or differential inhibition of brain protein synthesis.

Aging↗
PubMed2002

Gamma-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells.

The gamma-herpesviruses are oncogenic B cell lymphotrophic viruses that establish life-long latency in the host. Murine gamma-herpesvirus 68 (MHV-68) infection of mice represents a unique system for analyzing gamma-herpesvirus latency in splenic B cells at different stages of infection. After intranasal infection with MHV-68 we analyzed the establishment of latency 14 days after infection, and the maintenance of latency 3 months after infection in different purified subpopulations of B cells in the spleen. The data show that MHV-68 latency is mainly established in germinal center B cells and that long-term latency is preferentially maintained in two different subsets of isotype-switched B cells, germinal center and memory B cells. Cell cycle analysis indicates that MHV-68 is located in both cycling and resting isotype-switched B cells. Analysis of viral gene expression showed that both lytic and latent viral transcripts were differentially expressed in germinal center and memory B cells during long-term latency. Together, these observations suggested that gamma-herpesviruses exploit the B cell life cycle in the spleen.

Animals↗
PubMed2005

Selecting B cells and plasma cells to memory.

Humoral immunity appears to be based on immunological memory provided by memory plasma cells, which secrete protective antibodies, and memory B cells, which react to antigen challenge by differentiating into plasma cells. How these differentiation pathways relate to each other, how cells are selected into these memory populations, and how these populations are maintained remains enigmatic.

Animals↗
PubMed2003

[Memory in the grip of emotions and stress: a necessarily harmful impact?].

While intense negative events are vividly recalled, information learned during stressful situations is poorly remembered. These differential effects of emotions and stress on memory have been attributed to the physiological manifestations generated during those affective states. Intense emotional and stressful events trigger the secretion of catecholamines and of glucocorticoids, in particular. These hormones would be modulatory agents of memory functions. In the first part of this paper, we review the specific effects emotions and stress have on memory. We then summarize the psychological and biological determinants responsible for these effects. Finally, we discuss different methodological issues that could explain the discrepancy found between the impact of emotions and stress on memory. Defining more precisely the effects emotion and stress have on memory will lead to a better comprehension of the cognitive problems that characterize patients dealing with emotional turmoil, such as patients suffering from depression or post-traumatic stress disorder.

Amygdala↗
PubMed2002

The effect of glucose administration and the emotional content of words on heart rate and memory.

The effects of glucose administration and emotionality of target material on heart rate and memory were examined in a double-blind, placebo-controlled, balanced crossover study. Memory for neutral and emotional words was tested in 20 young adults following a glucose drink and a placebo. Heart rate and blood glucose were also measured. Emotional words were recalled and recognized better than neutral words in both drink conditions but there was no direct effect of drink type on memory. During the neutral word memory tasks, similar heart rate deceleration was observed in both drink conditions. However, during the processing of emotional material, heart rates were lowered in the placebo condition and relatively increased in the glucose condition. These results further differentiate the physiological responses involved during memory for affective and neutral material.

Adult↗
PubMedDate not supplied

[Clozapine: neuropsychological and neuroimaging studies].

The purpose of this work is to review the main investigations on the cognitive and cerebral effects of clozapine treatment in schizophrenic patients. We remark the differential effects in respect to other neuroleptics. Memory is the neuropsychological function more widely investigated. Clozapine produces visual memory impairment, but not the verbal memory deficit observed following the classical neuroleptic treatment. The effect of clozapine in the cortico-subcortical circuitry points to a differential effects on frontal lobe functions. It has been observed positive effects in controlled verbal fluency and also in visuoconstructive functions. However, in these studies retest effects are not controlled. There are several magnetic resonance imaging works that found a decrease of caudate nuclei volume, in contrast to the increase observed after treatment with classical neuroleptics. The differential effects on neuropsychological functions may be caused by the differential action of antipsychotics on the fronto-estriatal structures. In the future research it is necessary to perform studies including together neuropsychological and functional neuroimaging data in order to clarify the mechanisms responsible of positive and negative psychopharmacological effects.

Antipsychotic Agents↗
PubMed2005

A transfer appropriate processing approach to investigating implicit memory for emotional words in the cerebral hemispheres.

Forty undergraduate students participated in two experiments designed to investigate the impact of perceptual and conceptual encoding manipulations on implicit memory for emotional words in each cerebral hemisphere. Adopting a transfer appropriate processing approach, the encoding manipulations were designed to promote processing of the surface features of stimuli in Experiment 1, and their semantic meaning in Experiment 2. In both experiments, participants completed the designated encoding task, followed by a lexical decision task where primed and unprimed words were presented to the left (LVF) and right visual fields (RVF). In Experiment 1, implicit memory was observed for RVF presentations of words primed according to their perceptual features. Word valence did not impact on visual field of presentation for primed or unprimed words. In Experiment 2, participation in the conceptual encoding task differentially impacted on processing and implicit memory for emotional words presented in the LVF, where priming the conceptual meaning of words facilitated the processing of positive, relative to negative and non-emotional words. In addition, implicit memory for conceptually primed negative words was reflected in inhibition of primed relative to unprimed negatively valenced words presented in the LVF. In contrast, for RVF presentations, there was evidence of implicit memory for conceptually primed non-emotional words, but not for emotional words. The results are generally consistent with the right hemisphere model of emotion, which posits greater right hemisphere involvement in both the processing and implicit memory of emotional stimuli. The results also support Nagae and Moscovitch's suggestion [Nagae, S., & Moscovitch, M. (2002). Cerebral hemispheric differences in memory of emotional and non-emotional words in normal individuals. Neuropsychologia, 40, 1601-1607] that level of processing be incorporated into studies examining the veracity of the right hemisphere and valence models of emotional processing. The study demonstrated the usefulness of adopting a transfer appropriate processing approach to investigating memory for word valence in each hemisphere.

Cerebral Cortex↗
PubMed1998

Capacity limitations in short-term memory in schizophrenia: tests of competing hypotheses.

BACKGROUND: Capacity limitation theories have proved to be surprisingly resilient in characterizing some of the cognitive deficits in schizophrenia. However, this perspective has not generally been applied to short-term verbal memory tasks. We explored this issue by first attempting to ascertain if gross misallocations of processing resources might explain impairments in short-term memory in schizophrenia on a classic digit span task and in a second study by attempting to determine what effects delay and memory set size had on a divided attention short-term verbal memory paradigm. METHODS: In the first study 16 patients with schizophrenia and 21 normal controls received 40 trials of a three digit task and 20 trials of a six digit span task. As the absolute number of digits presented and duration of presentation in two conditions were identical, subjects thus had equivalent 'opportunities' to make errors if distraction, in the sense of misallocation of cognitive resources, were at the root of poor performance. In the second study 15 patients with schizophrenia and 15 normal controls were tested in conditions in which two, four or six words were presented and in which rehearsal was prevented by an interference task (colour naming) for delays of 5, 10 or 15 s. RESULTS: Patients had disproportionate difficulty on the six digit rather than the three digit condition, suggesting that deficits in the verbal working memory short-term store may not be the result of attentional factors. In the second study, patients' performance was differentially worsened by the interference task, by memory set size (i.e. a capacity limitation) and by delay, a measure of decay rate. CONCLUSIONS: In concert, these studies demonstrate that schizophrenia patients have difficulties on verbal short-term memory span tasks not because of misallocation of resources, but rather because of limitations in 'representational capacity' and maintenance of information over delays.

Adult↗
PubMed1994

Differential effect of transforming growth factor-beta 1 on the activation of human naive and memory CD4+ T lymphocytes.

Transforming growth factor-beta 1 (TGF-beta 1) can have stimulatory or inhibitory effects on cell growth. For several cell types, the effect of TGF-beta 1 was found to correlate with the differentiation stage of the cells and the presence of other cytokines. We have studied here the influence of TGF-beta 1 on CD4+ T cell activation in relation to the differentiation stage of the cells by evaluating the effect of TGF-beta 1 on the proliferative responses of purified CD4+CD45RA+ (unprimed) and CD4+CD45RO+ (primed) lymphocytes. Under certain conditions, TGF-beta 1 exerted a co-stimulatory effect on peripheral blood CD4+CD45RA+ T cells whereas the outgrowth of CD4+CD45RO+ T cells was suppressed in any activation system tested. The enhancement of proliferative responses by TGF-beta 1 in TCR/CD3 or CD2 stimulated cultures of CD45RA+ cells involved up-regulation of CD25 expression and was dependent on the presence of exogenous IL-2 or CD28 mAbs; IL-7 driven proliferative responses were suppressed by TGF-beta 1. These observations were confirmed in experiments with purified cord blood (CB) CD4+ T cells inasmuch as addition of TGF-beta 1 caused a 2- to 7-fold increase in IL-2 driven proliferative responses of these cells. Finally we show that, in contrast to the effect of TGF-beta 1 during primary stimulation of CD CD4+ T cells, TGF-beta 1 suppressed T cell proliferation for approximately 40% in secondary cultures of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Differential contributions of the parahippocampal place area and the anterior hippocampus to human memory for scenes.

Past neuroimaging research has identified a parahippocampal place area (PPA) in the posterior medial temporal lobe (MTL), which responds preferentially to visual scenes and plays a role in episodic memory for this class of stimuli. In the present positron emission tomography study, we examined to what extent the functional characteristics of the PPA resemble those of other, more anterior MTL regions across various learning and recognition-memory tasks. We also determined whether the involvement of the PPA in recognition of previously studied scenes is specific to a particular type of scene information. We found that, like the PPA, anterior hippocampal regions showed a novelty response (higher activation for novel than repeated scenes) and a stimulus-related response (higher activation for scenes than objects) during learning, indicating that MTL structures other than the PPA contribute to the encoding of novel stimulus relationships in scenes. However, these anterior hippocampal regions showed no involvement during recognition of either spatial or nonspatial information contained in scenes. The PPA, by contrast, was consistently involved in recognition of all types of scene details, presumably through interactions with co-activated parietal and occipitotemporal cortices. We suggest that MTL contributions from the PPA are sufficient to support recognition of scenes when the task can be based on a perceptually based familiarity process.

Adult↗
PubMed1997

Nasal lymphoid tissue, intranasal immunization, and compartmentalization of the common mucosal immune system.

Mucosal application of vaccines with an appropriate adjuvant can induce immune responses at both systemic and mucosal sites, and therefore may prevent not only infectious disease, but also colonization of mucosal surfaces. Intranasal is more effective than intragastric immunization at generating earlier and stronger mucosal immune response. Nasal lymphoid tissue (NALT) and its local draining lymph nodes may retain long-term immune memory. IgA isotype switching, and the differentiation and maturation of IgA antibody-secreting cells (ASC) may occur before these cells migrate out of NALT, whereas IgG ASC responses require passage of the cells through draining lymph nodes of the NALT. Knowledge of whether immune memory cells can recirculate to and reside in the inductive sites other than their origin after encountering antigen will be helpful for understanding the compartmentalization of the common mucosal immune system as well as for determining the best route for delivering a mucosal vaccine against a particular pathogen.

Administration, Intranasal↗
PubMed2000

Pharmacological demonstration of the differential involvement of protein kinase C isoforms in short- and long-term memory formation and retrieval of one-trial avoidance in rats.

RATIONALE: The hippocampal protein kinase C (PKC) family is involved in the early events of consolidation of long-term potentiation (LTP) and long-term memory (LTM). Results so far are indecisive about which PKC isoform is involved and as to whether any of them plays a role in short-term memory (STM) processes, which have recently been shown to be separate from those of LTM in the hippocampus-dependent one-trial step-down inhibitory avoidance task. OBJECTIVES: To measure the effect of two PKC inhibitors, one (Gö 6976) selective to the calcium-dependent isoforms alpha and beta I, and the other (Gö 7874) unspecific as to PKC isoforms on the formation and retrieval of STM and LTM of one-trial inhibitory avoidance. METHODS: Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus were trained in one-trial step-down inhibitory avoidance. The effect of these two drugs on STM and LTM formation was investigated as follows. Animals were infused 10 min before or 50, 110, or 170 min after inhibitory avoidance training with a vehicle (2% dimethylsulfoxide in saline), or with Gö 6976 (0.92 nM or 4.6 nM) or Gö 7874 (1.96 nM or 8 nM) dissolved in the vehicle. Infusion volume was 0.5 microliter in all cases. Animals were tested 1.5 h and 3 h after training for STM and at 24 h for LTM. In order to study the effects of these compounds on retrieval, they were infused into the hippocampus 10 min prior to STM testing at 3 h (see above) or 10 min before LTM testing at 24 h. In addition, the effect of Gö 6976 and Gö 7874 was studied on general activity measured in an open field, and on performance in an elevated plus maze. RESULTS: STM was suppressed by 4.6 nM Gö 6976 given 10 min before or 50 min after training. LTM was cancelled by the higher dose of the two compounds given 10 min before, or 50 min or 110 min after training. None of the two compounds infused 170 min post-training affected the retrieval of STM measured 10 min later. However, both compounds given 10 min before testing inhibited the retrieval of LTM measured at 24 h. This effect cannot be attributed to influences on locomotor activity or anxiety levels, since the drugs had no effect on performance in the open field but were mildly "anxiogenic" (pro-conflict) and reduced the number of entries into open and closed arms and rearings. CONCLUSIONS: LTM consolidation requires in part alpha- and/or beta 1-PKC and in part other PKC isoforms. STM formation requires instead only alpha and/or beta I-PKC and during a more limited period of time. In addition, PKC appears not to be necessary for the retrieval of STM, but is crucial for the retrieval of LTM. These findings further point to a biochemical separation of STM and LTM, as ascertained in numerous previous studies.

Animals↗
PubMed2004

Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin.

Ghrelin is a peptide hormone produced and secreted from the stomach. Hypothalamic injection of the peptide increases food intake but it is not known if the peptide affects other brain regions. We measured several behavioral parameters such as anxiety (elevated plus maze), memory retention (step down test), and food intake after injections of different doses of the peptide in the hippocampus, amygdala, and dorsal raphe nucleus (DRN). The injection of ghrelin in the hippocampus and DRN significantly and dose dependently increased food intake in relation to controls rats, while injections into the amygdala did not affect the food intake. We also show for the first time that ghrelin clearly and dose dependently increases memory retention in the hippocampus, amygdala, and DRN. Moreover, ghrelin at different potencies induced anxiogenesis in these brain structures while the highest dose of 3 nmol/microl was effective in all of them. The comparison of sensitivity of each brain structure indicates a specific role of them for each of the behaviors studied. The results provide new insight in to the anatomical substrate and the functional role of extrahypothalamic ghrelin targets in the CNS.

Amygdala↗