Long-term social recognition memory in adult male rats: factor analysis of the social and non-social behaviors

A modified version of the intruder-resident paradigm was used to investigate if social recognition memory lasts at least 24 h. One hundred and forty-six adult male Wistar rats were used. Independent groups of rats were exposed to an intruder for 0.083, 0.5, 2, 24, or 168 h and tested 24 h after the first encounter with the familiar or a different conspecific. Factor analysis was employed to identify associations between behaviors and treatments. Resident rats exhibited a 24-h social recognition memory, as indicated by a 3- to 5-fold decrease in social behaviors in the second encounter with the same conspecific compared to those observed for a different conspecific, when the duration of the first encounter was 2 h or longer. It was possible to distinguish between two different categories of social behaviors and their expression depended on the duration of the first encounter. Sniffing the anogenital area (49.9% of the social behaviors), sniffing the body (17.9%), sniffing the head (3%), and following the conspecific (3.1%), exhibited mostly by resident rats, characterized social investigation and revealed long-term social recognition memory. However, dominance (23.8%) and mild aggression (2.3%), exhibited by both resident and intruders, characterized social agonistic behaviors and were not affected by memory. Differently, sniffing the environment (76.8% of the non-social behaviors) and rearing (14.3%), both exhibited mostly by adult intruder rats, characterized non-social behaviors. Together, these results show that social recognition memory in rats may last at least 24 h after a 2-h or longer exposure to the conspecific.

Long-term memory in financial prices: evidence from the Dutch stock market returns

Prepared for presentation at the Portuguese Finance Network International Conference 2014, Vilamoura, Portugal, June 18-20

Genetic influences on long-term memory control : COMT and retrieval-induced forgetting

Magdeburg, Univ., Med. Fak., Diss., 2014

Long-term persistence of HIV-1 vaccine-induced CD4+CD45RA-CD62L-CCR7- memory T-helper cells.

OBJECTIVE: To determine in chimpanzees if candidate HIV-1 subunit protein vaccines were capable of eliciting long-lasting T-cell memory responses in the absence of viral infection, and to determine the specific characteristics of these responses. DESIGN: A longitudinal study of cell-mediated immune responses induced in three chimpanzees following immunization with subunit envelope glycoproteins of either HIV-1 or herpes simplex virus (HSV)-2. Following these pre-clinical observations, four human volunteers who had been immunized 7 years previously with the same HIV-1 vaccine candidate donated blood for assessment of immune responses. METHODS: Responses were monitored by protein and peptide based ELISpot assays, lymphocyte proliferation, and intracellular cytokine staining. Humoral responses were assessed by enzyme-linked immunosorbent assay and virus neutralization assays. RESULTS: Although antigen (Ag)-specific CD4 T-cell responses persisted for at least 5 years in chimpanzees, CD8 T-cell responses were discordant and declined within 2 years. Detailed cellular analyses revealed that strong Th1 in addition to Th2 type responses were induced by AS2/gp120 and persisted, whereas CD8 T-cell memory declined in peripheral blood. The specificity of both Th and cytotoxic T-lymphocyte responses revealed that the majority of responses were directed to conserved epitopes. The remarkable persistence of Ag-specific CD4 T-cell memory was characterized as a population of the CD45RA-CD62L-CCR7- "effector phenotype" producing the cytokines IFNgamma, IL-2 and IL-4 upon epitope-specific recognition. Importantly, results in chimpanzees were confirmed in peripheral blood of one of four human volunteers studied more than 7 years after immunization. CONCLUSION: These studies demonstrate that epitope-specific Th1 and Th2 cytokine-dependent Th responses can be induced and maintained for longer than 5 years by immunization with subunit proteins of HIV-1.

Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guérin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice.

BACKGROUND: Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines. RESULTS: In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-γ and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses. CONCLUSION: The increased IFN-γ-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.

gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.

Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.05-8.9%). Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy. Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide. However, correlated functional and phenotype analysis of IVS-expanded postvaccine CD8(+) T cells demonstrated the proliferation of functionally anergic gp100(209-2M)- tetramer(+) CD8(+) T cells in several patients and also indicated interpatient variability of gp100(209-2M) stimulated T-cell proliferation. Flow cytometry analysis of cryopreserved postvaccine PBMCs from representative patients showed that the majority of tetramer(+) CD8+ T cells (78.1 +/- 4.2%) had either an "effector" (CD45 RA(+)/CCR7(-)) or an "effector-memory" phenotype (CD45RA(-)/CCR7(-)). Notably, analysis of PBMCs collected 12-24 months after vaccine therapy demonstrated the durable presence of gp100(209-2M)-specific memory CD8(+) T cells with high proliferation potential. Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component. The data further support the combined use of tetramer binding and functional assays in correlated ex vivo and IVS settings as a standard for immunomonitoring of cancer vaccine patients.

Astrocyte-neuron lactate transport is required for long-term memory formation.

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation.

Deficit in memory consolidation (abnormal forgetting rate) in childhood temporal lobe epilepsy. Pre and postoperative long-term observation.

Deficits in memory consolidation have been reported in adult patients with epilepsy but, not to our knowledge, in children. We report the long-term follow-up (9 y. o. to 18 y. o.) of a boy who suffered from temporal lobe epilepsy and underwent a left temporal lobectomy with amygdalo-hippocampal resection at the age of 10. He showed an abnormal forgetting rate when trying to encode new information and a significant deficit for retrieving remote episodic memories (when compared with his twin brother), both consistent with a consolidation disorder. His memory condition slightly improved after cessation of the epilepsy, nevertheless did not normalize. No standard memory assessment could pinpoint his memory problem, hence an adapted methodology was needed. We discuss the nature of the memory deficit, its possible causes and its clinical implications.

Learning-induced gene expression in the heads of two Nasonia species that differ in long-term memory formation.

BACKGROUND: Cellular processes underlying memory formation are evolutionary conserved, but natural variation in memory dynamics between animal species or populations is common. The genetic basis of this fascinating phenomenon is poorly understood. Closely related species of Nasonia parasitic wasps differ in long-term memory (LTM) formation: N. vitripennis will form transcription-dependent LTM after a single conditioning trial, whereas the closely-related species N. giraulti will not. Genes that were differentially expressed (DE) after conditioning in N. vitripennis, but not in N. giraulti, were identified as candidate genes that may regulate LTM formation. RESULTS: RNA was collected from heads of both species before and immediately, 4 or 24 hours after conditioning, with 3 replicates per time point. It was sequenced strand-specifically, which allows distinguishing sense from antisense transcripts and improves the quality of expression analyses. We determined conditioning-induced DE compared to naïve controls for both species. These expression patterns were then analysed with GO enrichment analyses for each species and time point, which demonstrated an enrichment of signalling-related genes immediately after conditioning in N. vitripennis only. Analyses of known LTM genes and genes with an opposing expression pattern between the two species revealed additional candidate genes for the difference in LTM formation. These include genes from various signalling cascades, including several members of the Ras and PI3 kinase signalling pathways, and glutamate receptors. Interestingly, several other known LTM genes were exclusively differentially expressed in N. giraulti, which may indicate an LTM-inhibitory mechanism. Among the DE transcripts were also antisense transcripts. Furthermore, antisense transcripts aligning to a number of known memory genes were detected, which may have a role in regulating these genes. CONCLUSION: This study is the first to describe and compare expression patterns of both protein-coding and antisense transcripts, at different time points after conditioning, of two closely related animal species that differ in LTM formation. Several candidate genes that may regulate differences in LTM have been identified. This transcriptome analysis is a valuable resource for future in-depth studies to elucidate the role of candidate genes and antisense transcription in natural variation in LTM formation.

Accessing forgotten memory traces from long-term memory via visual movements

Because memory retrieval often requires overt responses, it is difficult to determine to what extend forgetting occurs as a problem in explicit accessing of long-term memory traces. In this study, we used eye-tracking measures in combination with a behavioural task that favoured high forgetting rates to investigate the existence of memory traces from long-term memory in spite of failure in accessing them consciously. In 2 experiments, participants were encouraged to encode a large set of sound-picture56 location associations. In a later test, sounds were presented and participants were instructed to visually scan, before a verbal memory report, for the correct location of the associated pictures in an empty screen. We found the reactivation of associated memories by sound cues at test biased oculomotor behaviour towards locations congruent with memory representations, even when participants failed to consciously provide a memory report of it. These findings reveal the emergence of a memory-guided behaviour that can be used to map internal representations of forgotten memories from long-term memory.

Long-term habituation (LTH) in the crab Chasmagnathus: a model for behavioral and mechanistic studies of memory

A decade of studies on long-term habituation (LTH) in the crab Chasmagnathus is reviewed. Upon sudden presentation of a passing object overhead, the crab reacts with an escape response that habituates promptly and for at least five days. LTH proved to be an instance of associative memory and showed context, stimulus frequency and circadian phase specificity. A strong training protocol (STP) (³15 trials, intertrial interval (ITI) of 171 s) invariably yielded LTH, while a weak training protocol (WTP) (£10 trials, ITI = 171 s) invariably failed. STP was used with a presumably amnestic agent and WTP with a presumably hypermnestic agent. Remarkably, systemic administration of low doses was effective, which is likely to be due to the lack of an endothelial blood-brain barrier. LTH was blocked by inhibitors of protein and RNA synthesis, enhanced by protein kinase A (PKA) activators and reduced by PKA inhibitors, facilitated by angiotensin II and IV and disrupted by saralasin. The presence of angiotensins and related compounds in the crab brain was demonstrated. Diverse results suggest that LTH includes two components: an initial memory produced by spaced training and mainly expressed at an initial phase of testing, and a retraining memory produced by massed training and expressed at a later phase of testing (retraining). The initial memory would be associative, context specific and sensitive to cycloheximide, while the retraining memory would be nonassociative, context independent and insensitive to cycloheximide

Differential role of entorhinal and hippocampal nerve growth factor in short- and long-term memory modulation

We studied the effects of infusion of nerve growth factor (NGF) into the hippocampus and entorhinal cortex of male Wistar rats (250-300 g, N = 11-13 per group) on inhibitory avoidance retention. In order to evaluate the modulation of entorhinal and hippocampal NGF in short- and long-term memory, animals were implanted with cannulae in the CA1 area of the dorsal hippocampus or entorhinal cortex and trained in one-trial step-down inhibitory avoidance (foot shock, 0.4 mA). Retention tests were carried out 1.5 h or 24 h after training to measure short- and long-term memory, respectively. Immediately after training, rats received 5 µl NGF (0.05, 0.5 or 5.0 ng) or saline per side into the CA1 area and entorhinal cortex. The correct position of the cannulae was confirmed by histological analysis. The highest dose of NGF (5.0 ng) into the hippocampus blocked short-term memory (P < 0.05), whereas the doses of 0.5 (P < 0.05) and 5.0 ng (P < 0.01) NGF enhanced long-term memory. NGF administration into the entorhinal cortex improved long-term memory at the dose of 5.0 ng (P < 0.05) and did not alter short-term memory. Taken as a whole, our results suggest a differential modulation by entorhinal and hippocampal NGF of short- and long-term memory.

Errors in nonword repetition: bridging short- and long-term memory

According to the working memory model, the phonological loop is the component of working memory specialized in processing and manipulating limited amounts of speech-based information. The Children's Test of Nonword Repetition (CNRep) is a suitable measure of phonological short-term memory for English-speaking children, which was validated by the Brazilian Children's Test of Pseudoword Repetition (BCPR) as a Portuguese-language version. The objectives of the present study were: i) to investigate developmental aspects of the phonological memory processing by error analysis in the nonword repetition task, and ii) to examine phoneme (substitution, omission and addition) and order (migration) errors made in the BCPR by 180 normal Brazilian children of both sexes aged 4-10, from preschool to 4th grade. The dominant error was substitution [F(3,525) = 180.47; P < 0.0001]. The performance was age-related [F(4,175) = 14.53; P < 0.0001]. The length effect, i.e., more errors in long than in short items, was observed [F(3,519) = 108.36; P < 0.0001]. In 5-syllable pseudowords, errors occurred mainly in the middle of the stimuli, before the syllabic stress [F(4,16) = 6.03; P = 0.003]; substitutions appeared more at the end of the stimuli, after the stress [F(12,48) = 2.27; P = 0.02]. In conclusion, the BCPR error analysis supports the idea that phonological loop capacity is relatively constant during development, although school learning increases the efficiency of this system. Moreover, there are indications that long-term memory contributes to holding memory trace. The findings were discussed in terms of distinctiveness, clustering and redintegration hypotheses.