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[Learning characteristics and long-term memory in rhesus macaques].

The use of entropy of choices distribution in studying the processes of learning and long-term memory in rhesus monkeys during differentiation of periodic and non-periodic visual stimuli, showed that the transition from the unlearned state to the learned one proceeds not gradually but in two stages; the first stage--the accumulation of information and externally random behaviour, the second stage--rapid transition to the learned behaviour. For "filters" selective to spatial frequency, the change of stimuli orientation leads to an increase of the behaviour entropy. For "filters" selective to the bar width, the entropy practically does not change. During prolonged storage of acquired information, in the long-term memory, its partial loss takes place leading to an increase of the behaviour entropy. The difference between the entropy determined directly after the learning and that determined again after a prolonged storage of the memorized habit characterizes the quantity of information lost during the storage period.

Animals↗
PubMed2006

Processing of autobiographical memory retrieval cues in borderline personality disorder.

BACKGROUND: Affective dysregulation in borderline personality disorder (BPD) in response to both external stimuli and memories has been shown to be associated with functional alterations of limbic and prefrontal brain areas. This study aimed to examine neuronal networks involved in autobiographical memory retrieval using standardized stimuli that gain autobiographical significance by illustrating marked solitary and social situations of human life. METHODS: Using event-related functional Magnetic Resonance Imaging (fMRI), we examined the processing of pictures from the Thematic Apperception Test (TAT) in 14 BPD patients and 14 controls. RESULTS: In both groups, TAT stimuli activated brain areas known to be involved in autobiographical memory retrieval. BPD subjects lacked differential amygdala, orbitofrontal and cingulate activations for TAT versus neutral stimuli. In the TAT condition, compared to controls, BPD subjects displayed increased BOLD responses in the bilateral orbitofrontal and insular regions, in the left anterior cingulate and medial prefrontal cortex, as well as in the parietal and parahippocampal areas, consistent with a more aversive and arousing experience assessed by self-reports. CONCLUSIONS: Increased BOLD responses during TAT processing in BPD subjects were in line with previously reported changes in anterior cingulate and orbitofrontal cortices, which are known to be involved in memory retrieval. However, BPD subjects displayed hyperactivation in these areas for both TAT and neutral stimuli. The deficit of selective activation of areas involved in autobiographical memory retrieval suggests a general tendency towards a self-referential mode of information processing in BPD, or a failure to switch between emotionally salient and neutral stimuli.

Affect↗
PubMed2002

Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats.

We examined the performance of Long-Evans rats with 192 IgG-saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB) or nucleus basalis magnocellularis/substantia innominata (NBM/SI), which removed cholinergic projections mainly to hippocampus or neocortex, respectively. We studied the effects of these lesions on anterograde and retrograde memory for a natural form of hippocampal-dependent associative memory, the social transmission of food preference. In a study of anterograde memory, MS/VDB lesions did not affect the immediate, 24-h or 3-week retention of the task. In contrast, NBM/SI lesions severely impaired immediate and 24-h retention. In a study of retrograde memory in which rats acquired the food preference 5 days or 1 day before surgery and they were tested 10-11 days after surgery, MS/VDB-lesioned rats showed striking memory deficits for the preference acquired at a long delay (5 days) before surgery, although all lesioned rats exhibited poorer retention on both retest sessions than on their pretest performance. Subsequent testing of new anterograde learning in these rats revealed no disrupting effects of lesions on a standard two-choice test. When rats were administered a three-choice test, in which the target food was presented along with two more options, NBM/SI-lesioned rats were somewhat impaired on a 24-h retention test. These results provide evidence that NBM/SI and MS/VDB cholinergic neurons are differentially involved in a social memory task that uses olfactory cues, suggesting a role for these neurons in acquisition and consolidation/retrieval of nonspatial declarative memory.

Amnesia, Anterograde↗
PubMed2005

Differential expression of chemokine receptors on human IgA+ and IgG+ B cells.

Organ-specific lymphocyte homing is dependent on the expression of tissue-specific homing receptors and selected chemokine receptors. During the effector phase of an immune response, IgA and IgG antibody-secreting cells (ASC) are differently distributed in the body. Still, B cell expression of L-selectin and the mucosal homing receptor integrin alpha4beta7 is not related to the isotype produced, but only to the site of antigen encounter. In this study, we examined if differences in chemokine responsiveness between IgA+ and IgG+ B cells could explain their different tissue localization. Circulating CD19+ B cells were isolated and their expression of IgA, IgG, and selected chemokine receptors was determined by flow cytometry. Few Ig+ cells expressed CCR2, CCR3, or CCR9, and there was no difference in the expression of these receptors between IgA+ and IgG+ cells. In contrast, CCR4, CCR5, and CXCR3 was expressed on significantly more IgG+ than IgA+ cells. The function of chemokine receptors on memory B cells and ASC was then tested in the transwell system. IgG+ memory cells migrated to a higher extent than IgA+ cells towards the CXCR3 ligand CXCL11/I-TAC, while there was only a small migration towards the CCR4 ligand CCL17/TARC and the CCR9 ligand CCL25/TECK. ASC migrated poorly to all chemokines tested. In conclusion, this study shows that IgG+ and IgA+ memory B cells have a differential expression of the Th1 associated chemokine receptor CXCR3, as well as of CCR4 and CCR5. In contrast, none of the studied chemokine receptors was preferentially expressed by IgA+ cells.

Antibody-Producing Cells↗
PubMed2003

The GABAB receptor and recognition memory: possible modulation of its behavioral effects by the nitrergic system.

Functional activation of the GABA(B) receptor inhibits learning and memory processes, though discrepant findings, in this context, have also been reported. The present study was designed to investigate the role of the GABA(B) receptor on recognition memory in the rat. For this purpose, the effects induced by the GABA(B) agonist baclofen and the GABA(B) antagonist P-(3-aminopropyl)-P-diethoxymethylphosphinic acid (CGP 35348) on memory were assessed by using the object-recognition task. In addition, the possible involvement of the nitrergic system on GABA(B) receptor's effects was also evaluated by using the same behavioral procedure. This is a working-memory paradigm based on the differential exploration of a new and familiar object. In a first dose-response study, baclofen (0.5, 2, and 4 mg/kg, i.p.), dose-dependently impaired animals' performance in this task, suggesting a modulation of acquisition and storage of information. CGP 35348 (100 and 300 mg/kg, i.p.), counteracted these baclofen-induced performance deficits. The nitric oxide donor molsidomine, at the dose of 4 but not 2 mg/kg, i.p, successfully antagonized the deficits on cognition induced by the highest dose of baclofen (4 mg/kg). These results indicate a) that the GABA(B) receptor is involved in recognition memory and b) that an NO component modulates the effects of the GABA(B) receptor on learning and memory.

Animals↗
PubMed2003

Effects of intention load and background context on prospective remembering: an event-related brain potential study.

Prospective remembering reflects the ability to realize intentions that must be delayed over some period of time. Recent evidence indicates that distinct modulations of the event-related brain potentials may be associated with the detection of a prospective memory cue (N300) and the recovery of an intention from memory (LPC, slow wave). The present experiments examined the degree to which these modulations were influenced by task manipulations that were expected to differentially influence cue detection and memory-related processes. Varying the number of intentions modulated the amplitude of a slow wave that may reflect memory-related processes. In contrast, varying the distinctiveness of the cues modulated the N300 and the early portion of the LPC indicating that this manipulation primarily influenced detection and categorization processes. These findings indicate that the N300, LPC and slow wave reflect functionally distinct processes associated with prospective memory.

Adolescent↗
PubMed1989

Memory processes and aging: a defect of automatic rather than controlled processes?

The effect of age (20-86) and/or cultural level is investigated from the point of view of Cognitive Psychology. The study was carried out with 75 subjects distributed into 5 age-ranges and 3 cultural levels. It involved the following memory tests: forced choice recognition of faces (Warrington, 1984) and of abstract paintings; Rey Figure; immediate free recall; final free recall; learning and retention of paired associates; learning with AB-AC-AB design to test for interference; Selective Reminding test of Buschke (1973); repeated free recall. Data where analysed, taking into account dozens of variables. As far as age is concerned, all the analyses converge toward the same conclusion: short-term memory is not significantly affected by age, while a clear distinction appears between two kinds of secondary memory. Secondary memory involved in the course of learning or in the retention of learning is unaffected by age. By contrast, secondary memory involved in the retention of an initial or single confrontation with test material is very much affected by age. Age might, therefore, differentially affect two kinds of secondary memory. It is suggested that, contrary to the view of certain authors, age mainly affects automatic secondary memory, whereas voluntary, conscious, controlled and effortful secondary memory, which could require a greater amount of 'mental energy' or attentional resource, is relatively well preserved with age.

Adult↗
PubMed2003

The perirhinal-entorhinal cortex, but not the hippocampus, is critical for expression of individual recognition in the context of the Coolidge effect.

The Coolidge effect is a phenomenon in which males show renewed sexual interest in a novel female following copulation to satiety with another female. In golden hamsters, this phenomenon depends on the ability to recognize conspecifics using chemosensory cues processed through the main olfactory system. Here we tested whether olfactory targets in the hippocampal system support this natural form of recognition memory. Male hamsters received ibotenic acid lesions of the perirhinal-entorhinal cortex (PR-ENT) or hippocampus (H) and were allowed to copulate to satiety with a female conspecific, then were presented with two anesthetized females, the familiar mate and an unfamiliar female that copulated with another male. Sham-operated and H-lesioned subjects preferentially investigated the novel female, indicating intact recognition of individual identity. By contrast, PR-ENT-lesioned males failed to discriminate familiar and novel females, and this deficit could not be attributed to abnormal copulatory behavior during mating. All subjects were able to detect and discriminate between female odors when presented in isolation during a habituation-discrimination test, indicating that behavioral deficits shown by PR-ENT males were not due to anosmia or a general investigatory deficit. Thus, the perirhinal-entorhinal cortex, but not the hippocampus, is critical for the recognition of familiar conspecifics in this naturalistic situation. This study reveals an essential role for the perirhinal-entorhinal cortex, but not the hippocampus, in a natural form of recognition memory within the social behavior of hamsters. The findings show a strikingly similar pattern to the effects of selective damage to the same brain regions on performance in standard recognition memory tasks by rats and monkeys. Therefore, the present data extend our understanding of the differential role of structures of the hippocampal memory system, showing continuity across species and between formal laboratory tests and the function of memory in natural social behavior.

Animals↗
PubMed2006

Functional imaging of working memory following normal sleep and after 24 and 35 h of sleep deprivation: Correlations of fronto-parietal activation with performance.

Working memory was evaluated after normal sleep, and at 24 and 35 h of sleep deprivation (SD) in 26 healthy young adults to examine the neural correlates of inter-individual differences in performance. The extent of performance decline was not significantly different between the two SD test periods although there was greater variability in performance at SD35. In both SD sessions, there was reduced task-related activation (relative to normal sleep) in both superior parietal regions and the left thalamus. Activation of the left parietal and left frontal regions after normal sleep was negatively correlated with performance accuracy decline from normal sleep to SD24 thus differentiating persons who maintained working memory performance following SD from those who were vulnerable to its effects.

Adult↗
PubMed2006

NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis.

In the adult brain, the expression of NT-3 is largely confined to the hippocampal dentate gyrus (DG), an area exhibiting significant neurogenesis. Using a conditional mutant line in which the NT-3 gene is deleted in the brain, we investigated the role of NT-3 in adult neurogenesis, hippocampal plasticity, and memory. Bromodeoxyuridine (BrdU)-labeling experiments demonstrated that differentiation, rather than proliferation, of the neuronal precursor cells (NPCs) was significantly impaired in DG lacking NT-3. Triple labeling for BrdU, the neuronal marker NeuN, and the glial marker GFAP indicated that NT-3 affects the number of newly differentiated neurons, but not glia, in DG. Field recordings revealed a selective impairment in long-term potentiation (LTP) in the lateral, but not medial perforant path-granule neuron synapses. In parallel, the NT-3 mutant mice exhibited deficits in spatial memory tasks. In addition to identifying a novel role for NT-3 in adult NPC differentiation in vivo, our study provides a potential link between neurogenesis, dentate LTP, and spatial memory.

Animals↗
PubMed1992

Electrodermal differentiation of deception: potentially confounding and influencing factors.

The demonstration of deception as a psychological process requires a comparison of physiological responding to questions answered honestly or deceptively, under conditions which differ only with respect to deception. Such electrodermal (skin conductance response (SCR) differentiation was recently reported in the Differentiation-of-Deception Paradigm. The present study had two empirical goals: (a) to assess the possible confounding role of retrieval-difficulty and novelty in producing the differentiation effect; (b) to ascertain any influencing effects of a memorial ('cumulative' mental load) and two motivational (Monetary-Incentive and Ego-Involvement) factors on the electrodermal differentiation phenomenon and on overall responding. In addition to the basic Deceptive vs. Honest manipulation of the Differentiation-of-Deception Paradigm, the present study varied, within 60 subjects, Question Type (easily retrieved Autobiographical vs. more difficult-to-retrieve Biographical). The two two-level motivational factors were varied between subjects. Finally, to assess the confounding issue, voice latency (VL), known to be sensitive to retrieval-difficulty, was measured in addition to SCR. SCRs to deceptive answers exceeded those to the honestly-answered questions, demonstrating the differentiation phenomenon. Results showed that although VL and SCR was significantly greater to Biographical than to Autobiographical questions, the differentiation effect emerged only in the SCR and not in VL, which suggests that memorial difficulty does not confound the electrodermal differentiation effect.

Adolescent↗
PubMed2004

Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion.

T cell homeostasis is a self-regulating process for maintaining the size of the peripheral T cell pool. Although dendritic cells (DCs) seem to be important in T cell homeostasis, the molecular regulation of DC-mediated T cell homeostasis is unknown. We show that human DCs activated by thymic stromal lymphopoietin (TSLP) induced a robust expansion of autologous CD4(+) T cell populations, which depended on self peptide-major histocompatibility complex. The proliferating T cells adopted and maintained a central memory polyclonal phenotype and could differentiate into T helper type 1 or type 2 effector cells. These results, together with findings of TSLP expression in epithelial cells of mucosal lymphoid tissues and thymus, indicate that TSLP is involved in DC-mediated CD4(+) T cell homeostasis.

Animals↗
PubMed2000

The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females.

RATIONALE: Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggested that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-band. OBJECTIVE: The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement (EHR) previously. METHODS: EHR (Progynova TS, transdermal estradiol; n=19) or placebo (n=18) was given for a period of 3 weeks to elderly healthy female subjects. Memory, frontal lobe functions (inhibition and planning) and visuospatial abilities (mental rotation) were tested before and after treatment. Estrogen plasma levels were measured to confirm the result of EHR. Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to mild mental stress. RESULTS: Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman (0.21+/-0.5 nmol/l). Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR. However, there was no effect of EHR on frontal lobe functions. The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage. EHR was found to increase the HPA response to task-induced stress, as indicated by an increase in cortisol plasma levels. CONCLUSIONS: The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the present study has demonstrated a differential effect of EHR on memory, visuospatial abilities and frontal lobe function.

Aged↗
PubMed2005

Regulatory events in early and late B-cell differentiation.

We are studying transcriptional control of critical developmental decision points in B lymphocytes. Commitment to the B-lymphocyte lineage is dependent on the transcriptional regulator Pax5 and committed B lymphocytes represent the first developmental stage when V(H)-to-DJ recombination occurs in the immunoglobulin (Ig) heavy chain locus. We summarize our recent studies showing that methylation of histone H3 lysine 9, a heterochromatic chromatin modification, is present in the Ig V(H) region in hematopoietic progenitors and in non-B lineage hematopoietic cells. Pax5 is both necessary and sufficient to remove this heterochromatic mark in B cells. Using genetically altered mice, we have shown that terminal differentiation of B cells to memory and Ig-secreting plasma cells depends on the transcriptional repressor Blimp-1. Recent studies demonstrating a requirement for Blimp-1 in the formation of pre-plasma memory B cells, Ig-secreting plasma cells as well as preliminary data suggesting a requirement for Blimp-1 in the maintenance of long-lived plasma cells are summarized. We also summarize our recent studies on the regulation of Blimp-1, showing direct repression by Bcl-6 and providing evidence for activation by NF-kappaB following toll-like receptor signaling.

Animals↗
PubMed2000

Neuromodulation of memory in the hippocampus by vasopressin.

The involvement of [Arg(8)]vasopressin in memory processes was analyzed in the hippocampal structure, since we have reported that this is one of the main central target structures of the vasopressin-enhancing effect on memory. This structure is functionally differentiated along its dorsoventral axis, and the expression of the vasopressinergic system is dependent upon whether the dorsal or ventral part of the hippocampus is involved. For this reason, the effect of vasopressin injected into hippocampus was evaluated on the basis of the site of injection. We have shown, using a Go-No Go visual discrimination task with mice that both parts of the hippocampus are involved in the effect of endogenous or exogenous vasopressin, but with higher sensitivity for the ventral part. Based on the expression of Fos protein following intracerebroventricular injection of vasopressin in unconditioned or conditioned mice, we confirmed the greater involvement of the ventral hippocampus in the enhancing effect of vasopressin on memory processes. The effect of the peptide seems specific, since only a few of the hippocampal cells that expressed Fos protein in the unconditioned mice did so in the conditioned mice (cells in the dentate gyrus and the CA3 hippocampal field). Moreover, we have shown that in the ventral hippocampus, vasopressin generates different behavioral effects whether treatment is performed at the beginning or in the middle of the learning process, suggesting that the mnemonic context is an important factor for understanding the effect of vasopressin on memory in the ventral hippocampus.

Animals↗
PubMed1984

Differential effects of frontal-lobe lesions on cognitive estimation and spatial memory.

Patients with unilateral frontal- or temporal-lobe excisions and normal control subjects were tested on the recall of objects and of their location in an array. An incidental-learning situation was used, in which the task was presented as a test of the ability to estimate the prices of the objects. Patients with right frontal-lobe lesions were the only group impaired on price estimation, but a correlation was obtained between error-score in price estimation and lesion-size for the left frontal-lobe group. In contrast to patients with extensive right hippocampal excisions, both frontal-lobe groups were accurate on location-recall when tested immediately and again 24 hr later.

Adolescent↗