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PubMed1998

Learning and memory in the SAMP8 mouse.

The SAMP8 (P8) mouse strain develops deficits in learning and memory relatively early in its lifespan. This review provides an overview of the age-related changes that occur in P8 mice. Behavioral studies with P8 mice show impaired acquisition and retention as early as 4 months of age. Deficits in acquisition and retention occur with both aversive and appetitive training tasks. Anatomical studies have detected a number of age-related changes that occur in the central nervous system of P8 mice. The age-related increase in amyloid beta protein is well correlated with the age-related decline in learning and memory. Antibody to amyloid beta protein injected prior to training alleviated impaired acquisition and retention, whereas post-training injections alleviated retention deficits in older P8 mice. Biochemical studies have detected numerous age-related changes with reduced NMDA receptor activity most closely related to impaired learning and memory in P8 mice. Pharmacological studies have found age-related functional changes in the ability of drugs to improve memory processing in P8 mice in the septum and the hippocampus. The specific pattern of pharmacological changes and the inferred change in neurotransmitter activity suggest that age-related impairment in memory processing may be due to impaired septohippocampal interactions. The proposal that P8 mice may be a useful model for studying the early phases of age-related dementia of the Alzheimer type, while still requiring considerable study, seems reasonable.

Aging↗
PubMed2001

Impairments of learning and memory following intracerebroventricular administration of AF64A in rats.

Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform from 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th day, but not 8th day. In the active avoidance for the pre-trained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for spatial cognition.

Animals↗
PubMed2006

Dunces and da Vincis: the genetics of learning and memory in Drosophila.

Progress towards amelioration and eventual cure of human cognitive disorders requires understanding the molecular signaling mechanisms that normally govern learning and memory. The fly Drosophila melanogaster has been instrumental in the identification of molecules and signaling pathways essential for learning and memory, because genetic screens have produced mutants in these processes and the system facilitates integrated genetic, molecular, histological and behavioral analyses. We discuss the behavioral paradigms available to assess associative learning and memory in the fly, the contributions learning and memory mutants have made to our understanding of the molecular mechanisms that govern learning and memory, and predictions stemming from the nature of the affected genes. Furthermore, we consider the multiple well-established behavioral assays available and the powerful molecular genetics of the fly with regard to development of models of human cognitive disorders and their pharmacological treatment.

Animals↗
PubMed2003

Learning and memory deficits in APP transgenic mouse models of amyloid deposition.

Several different transgenic APP mice develop learning and memory deficits. In some cases the mice have deficits very early in life, while in other instances the mice exhibit deficits only after they have aged and amyloid deposits have accumulated. In many cases, there is a correlation in individual mice of the same age and genotype between the extent of learning and memory deficits and the amounts of deposited amyloid found in the central nervous system. While superficially this might imply that the deposited material is somehow toxic to cognition, it is likely that deposited amyloid is also an index of the overall rate of amyloid production in each mouse. Rate of production would be expected to modify not only the amounts of deposited amyloid, but also other amyloid pools, including soluble, oligomeric, conjugated (e.g. ADDLs) and intracellular. Thus, the deposited material may be an integrated reflection of total A beta production, in addition to indicating the amounts in fibrillar forms. As such, it is conceivable that other A beta pools may be more directly linked to memory deficits. Thus far, the one manipulation found to mitigate the learning and memory deficits in APP transgenic mice is immunotherapy for A beta, either using active or passive immunization against the peptide. These data together with other findings are leading to a conclusion that the fibrillar A beta deposits are not directly linked to the memory deficits in mice, and that some other A beta pool, more readily diminished by immunotherapy, is more directly linked to the mechanisms leading to poor performance in learning and memory tasks.

Amyloid beta-Peptides↗
PubMed1990

Early inhibitory learning in the rat. I. Learning and memory development.

The present status of knowledge on early inhibitory learning and memory is presented. The inhibitory learning (passive avoidance) can be mastered by rat pups several hours after parturition, provided specific characteristics of the newborn organism and its neurobehavioral capabilities are respected. The curve of numbers of trials to criterion displays, as already reported earlier, a generally decreasing trend which is, however, interrupted by a temporary inversion in both strains studied, but at different time, taking place in Long Evans between postnatal day 1 and 2, which is shifted in Wistar pups one day later. Present data show significant learning differences between strains at postnatal days 1-4; from day 5 onward no significant differences are evidenced up to postnatal day 11. A reliable 24-hour memory shown by positive values of the retention index (RI) is revealed from postnatal day 4, having in Long Evans higher RI values. Moreover, high positive RIs of 24-hour memory are found in animals trained on the day just before the inversion of the learning development. It is conjectured that the indirect development of the early inhibitory learning is due to the developmental reorganization within CNS, and the necessity to find out its underlying mechanisms is emphasized.

Aging↗
PubMed2004

Interaction of BDNF/TrkB signaling with NMDA receptor in learning and memory.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play important roles in learning and memory. Memory acquisition is associated with an increase in BDNF mRNA and TrkB activation in specific brain areas. Pharmacologic and genetic deprivation of BDNF or TrkB results in an impairment of memory. Activation of the mitogen-associated protein kinase and phosphatidylinositol 3-kinase signaling pathways is involved in BDNF-dependent learning and memory. A frequent single nucleotide polymorphism in the targeting region of the human BDNF gene (val66met) is associated with poorer episodic memory and abnormal hippocampal neuronal function in humans. The interaction of BDNF/TrkB signaling with N-methyl-D-aspartate receptors is important for spatial learning and memory, and an Src-family tyrosine kinase Fyn may play a key role in this interaction by linking TrkB with NR2B.

Animals↗
PubMed1995

Effects of footshock-, psychological- and forced swimming-stress on the learning and memory processes: involvement of opioidergic pathways.

Modulation of learning and memory acquisition, retention and retrieval in the one trial passive avoidance learning task in mice by three inescapable stresses, i.e., footshock (FS), psychological (PSY) and forced swimming (SW) were investigated. Pre-, post-training and pre-test FS-stress (2 mA, 0.2 Hz, 1 sec for 30 min) and pre-training PSY-stress (communication box, 5 min) resulted in enhanced test latencies. On the contrary, SW-stress (20 degrees C, 5 min) immediately or 1 hr after training impaired retention latencies that tended to recover after 2 hr post-training SW-stress, suggesting that at least 2 hr are required to consolidate newly acquired information. In contrast, pre-stress naloxone (Nx), which did not affect FS- and PSY-stress induced facilitatory effects, returned to control levels the impaired retention latencies induced by SW-stress. Taken collectively, these results imply the involvement of an opioid-dependent mechanism in the modulation of memory by SW-stress and non-opioid in the case of FS- and PSY-stress. Furthermore, they suggest that different mechanisms are involved in stress-induced memory modifications and the production of stress-induced analgesia (SIA) since in the latter, FS and PSY but not SW stress produce Nx-sensitive antinociception.

Animals↗
PubMed2006

Does maternal prenatal stress adversely affect the child's learning and memory at age six?

Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50 boys, 62 girls, Age: M=6.7 years, SD=8.4 months), with the Test of Memory and Learning (TOMAL). Maternal stress levels were determined three times during pregnancy by self-report questionnaires. Furthermore, maternal saliva cortisol samples were used as a measure of hypothalamus-pituitary-adrenal axis functioning. Results of hierarchical multivariate regression analyses showed that maternal life events measured during the first part of pregnancy were negatively associated with the child's attention/concentration index, while controlling for overall IQ, gender, and postnatal stress. No associations were found between prenatal maternal cortisol and the offspring's learning and memory.

Adult↗
PubMed1996

The use of null mutant mice to study complex learning and memory processes.

A number of neural substrates have been proposed to mediate complex learning and memory processes in mammalian organisms. One strategy for testing the involvement of a particular gene in learning and memory is to create a mouse line with a null mutation in that gene. Recently, embryonic stem cell-based gene-targeted homologous recombination techniques have been employed to create a number of such mutant mouse lines that do not express interesting candidate genes. These animals have been examined for impairments in several complex learning paradigms which are known to depend on the integrity of the hippocampus. In this review several complex learning and memory paradigms are described, the techniques to create null mutants are reviewed, and the results of recent studies with null mutants are described. Finally, the limitations for interpretation of behavioral data using null mutants are discussed.

Animals↗
PubMedDate not supplied

Septohippocampal acetylcholine: involved in but not necessary for learning and memory?

The neurotransmitter acetylcholine (ACh) has been accorded an important role in supporting learning and memory processes in the hippocampus. Cholinergic activity in the hippocampus is correlated with memory, and restoration of ACh in the hippocampus after disruption of the septohippocampal pathway is sufficient to rescue memory. However, selective ablation of cholinergic septohippocampal projections is largely without effect on hippocampal-dependent learning and memory processes. We consider the evidence underlying each of these statements, and the contradictions they pose for understanding the functional role of hippocampal ACh in memory. We suggest that although hippocampal ACh is involved in memory in the intact brain, it is not necessary for many aspects of hippocampal memory function.

Acetylcholine↗
PubMed2005

Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory.

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

Animals↗
PubMed1995

Effects of bilingualism on verbal learning and memory in Hispanic adults.

The effect of bilingualism on qualitative aspects of verbal learning and memory was investigated. Equivalent list learning tests in English and Spanish were carefully constructed, and compared across two bilingual Hispanic groups of Mexican origin that differed in their level of English proficiency ("balanced" and "nonbalanced" bilinguals) and a group of monolingual English-speaking non-Hispanic subjects. Groups were matched for age, education, and gender composition. Nonbalanced bilinguals assessed in English utilized semantic clustering to the same extent as monolinguals, but learned fewer words overall, and demonstrated lower retention scores compared to monolinguals. Comparisons of groups assessed in their dominant languages, however, revealed no significant differences on any of the learning and memory indices examined. In addition to comparisons with standard clinical memory indices, assessment issues concerning bilingual individuals are addressed.

Adult↗
PubMed1992

Correlations of memory and learning with vision in aged patients before and after a cataract operation.

The connection between memory and learning with vision was investigated by studying 100 cataract operation patients, aged 71 to 76 years, 25 of them being men and 75 women. The cataract operation restored sufficient acuity of vision for reading (minimum E-test value 0.40) to 79% of the subjects. Short-term memory was studied with series of numbers, homogenic and heterogenic inhibition, and long sentences. Learning was tested with paired-associate learning and word learning. Psychological symptoms were measured on the Brief Psychiatric Rating Scale and personality on the Mini-Mult MMPI. Memory and learning improved significantly when vision was normalized after the cataract operation. Poor memory and learning scores correlated with monocular vision before the operation and with defects in the field of vision, due to glaucoma and exceeding 20%, postsurgery. Monocular vision and defects in the visual field caused a continuous sense of abnormalness, which impaired old people's ability to concentrate on tasks of memory and learning. Cerebrovascular disturbances, beginning dementia, and moderate psychological symptoms obstructed memory and learning on both test rounds. Depression was the most important psychological symptom contributing to poor memory and learning scores after the cataract operation. The memory and learning defects mainly reflected disturbances in memorizing.

Aged↗
PubMed1998

Re-examining the factor structure of the Wide Range Assessment of Memory and Learning: implications for clinical interpretation.

The intercorrelation matrices of the standardization sample of the Wide Range Assessment of Memory and Learning (WRAML), a multi-component measure of memory functioning in children ages 5 to 17 years, were submitted to a hierarchical exploratory principal factor analysis (PFA). The PFA solutions were examined and compared with the published principal components analysis (PCA) solutions with the goal of examining the validity of the clinical scale configuration (Verbal Memory, Visual Memory, and Learning) proposed by the test authors. Results of the PFA differ from the PCA and do not provide statistical support for the existing three-scale structure nor the division between memory and learning. Specific factor loadings on the majority of sub-tests are higher than the common factor loadings indicating low shared variance. The low communalities together with the poor interpretability of the factor structure suggests that the subtests should be interpreted clinically as unique entities first and secondarily as factors. Theoretical and practical implications of the findings are discussed.

Adolescent↗
PubMedDate not supplied

Dimensions of the hippocampus, memory, and learning in the ontogenesis of rats.

Damage to the hippocampus in 20-, 50-, and 110-day-old rats impairs the processes of learning and short-term memory in them. In 50-day-old rats, hippocampectomy has less of an influence on the process of learning and memory than for 20- and 110-day-old animals. The anatomic and physiological characteristics of the hippocampus in 20-day-old rats may be evidence of a special importance of this formation at the early stages of ontogenesis, when the cerebral cortex is still insufficiently mature and its associations with other structures have not been entirely formed. The nonlinear nature of the dependence of the disruption of learning in rats of different ages after hippocampectomy suggests that the function of the rat hippocampus undergoes changes during the process of individual development of the animal.

Age Factors↗
PubMed2005

[Effects of high +Gx during simulated spaceship emergency return on learning and memory in rats].

OBJECTIVE: To observe the effects of high +Gx during simulated spaceship emergency return on learning and memory in rats. METHOD: Thirty two male SD rats were randomly divided into control group, 7 d simulated weightlessness group, +15 Gx/180 s group and +15 Gx/180 s exposure after 7 d simulated weightlessness group, with 8 rats in each group. The changes of learning and memory in rats were measured after stresses by means of Y-maze test and step-through test. RESULT: In Y-maze test, as compared with control group, percentage of correct reactions decreased significantly (P<0.01) and reaction time increased significantly (P<0.01) in hypergravity after simulated weightlessness group at all time after stress; as compared with +15 Gx group or simulated weightlessness group, percentage of correct reactions decreased significantly (P< 0.05) and reaction time increased significantly (P< 0.05) immediately after stress. In step-through test, as compared with control group, total time increased significantly (P<0.01) in hypergravity after simulated weightlessness group at 1 d after stress; latent time decreased significantly (P<0.01) and number of errors increased significantly (P< 0.01) at all the time after stress. As compared with +15 Gx group, total time increased significantly (P<0.05) immediately, 1 d after stress. As compared with simulated weightlessness group, total time and number of errors increased significantly (P<0.05) immediately after stress. CONCLUSION: It is suggested that +15 Gx/180 s and simulated weightlessness may affect the ability of learning and memory of rats. Simulated weightlessness for 7 d can aggravate the effect of +Gx on learning and memory ability in rats.

Animals↗
PubMed2004

The performance of infants born preterm and full-term in the mobile paradigm: learning and memory.

BACKGROUND AND PURPOSE: By 3 to 4 months of age, infants born full-term and without known disease display associative learning and memory abilities in the mobile paradigm, where an infant's leg is tethered to a mobile such that leg kicks result in proportional mobile movement. The first purpose of this study was to examine the learning and memory abilities of a group of infants born full-term compared with those of a comparison group. Little is known about the learning and memory abilities in infants born preterm, a group at known risk for future impairments in learning and movement. The second purpose of this study was to determine if and when an age-adjusted group of infants born prematurely display associative learning and memory abilities over a 6-week period. SUBJECTS: Ten infants born full-term (38-42 weeks gestational age [GA]) and 10 infants born preterm (<33 weeks GA and <2,500 g) who were tethered and had control over the mobile movement were independently compared with a comparison group of 10 infants born full-term who were tethered and viewed a moving mobile but did not have control over the mobile movement. Infants in all 3 groups were seen at 3 to 4 months of age and were excluded from participation for any known visual or orthopedic diagnoses. METHODS: Infants were tested using the mobile conjugate reinforcement paradigm, where one leg is tethered to an overhead mobile such that kicking with that leg results in proportional mobile movement. The kicking rates of the full-term group and the preterm group were compared with their own initial (baseline) kicking rates and with those of the comparison group. RESULTS: After exposure to the conjugate relationship between kicking and mobile movement, the full-term group kicked more frequently compared with their own baseline levels and compared with the comparison group, fulfilling both criteria for learning and memory. In contrast, the preterm group did not increase their kicking rate according to both criteria. DISCUSSION AND CONCLUSION: These results suggest that infants born prematurely differ in their performance in the mobile paradigm as compared with age-matched infants born full-term. The mobile paradigm may provide clinicians with an important early assessment of infants' associative learning and memory abilities. Follow-up studies are needed, however, to further validate this paradigm as a clinical assessment tool.

Analysis of Variance↗
PubMed2001

Differential effects of enrichment on learning and memory function in NR2B transgenic mice.

It has been known that environmental enrichment leads to better learning and memory in mice. However, the molecular mechanisms are not known. In this study, we used the 10th-12th of the NR2B transgenic (Tg) lines, in which the NMDA receptor function is enhanced via the NR2B subunit transgene in neurons of the forebrain, to test the hypothesis of the involvement of NMDA receptor function in enrichment-induced better learning and memory. Consistent with our previous results, both larger long-term potentiation (LTP) in the hippocampus and superior learning and memory were observed in naive NR2B Tg mice even after the 10th-12th generation of breeding. After enrichment, wild-type mice exhibited overall improvement in their performances in contextual and cued conditioning, fear extinctions, and novel object recognition tasks. Interestingly, the same enrichment procedures could not further increase the performance of NR2B Tg mice in contextual conditioning, cued conditioning, or fear extinction, thereby indicating that enhanced NMDA receptor function can occlude these enrichment effects. However, we found that in the novel object recognition task enriched NR2B Tg mice exhibited much longer recognition memory (up to 1 week), compared to that (up to 3 days) in naive NR2B Tg mice. Furthermore, our biochemical experiments showed that enrichment significantly increased protein levels of GluR1, NR2B, and NR2A subunits of glutamate receptors in both wild-type and NR2B Tg mice. Therefore, our results suggest an interactive nature of molecular pathways involved in both environmental and genetic NMDA receptor manipulations for enhancing learning and memory.

Animals↗