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PubMed2002

Protein phosphatase 1 is a molecular constraint on learning and memory.

Repetition in learning is a prerequisite for the formation of accurate and long-lasting memory. Practice is most effective when widely distributed over time, rather than when closely spaced or massed. But even after efficient learning, most memories dissipate with time unless frequently used. The molecular mechanisms of these time-dependent constraints on learning and memory are unknown. Here we show that protein phosphatase 1 (PP1) determines the efficacy of learning and memory by limiting acquisition and favouring memory decline. When PP1 is genetically inhibited during learning, short intervals between training episodes are sufficient for optimal performance. The enhanced learning correlates with increased phosphorylation of cyclic AMP-dependent response element binding (CREB) protein, of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and of the GluR1 subunit of the AMPA receptor; it also correlates with CREB-dependent gene expression that, in control mice, occurs only with widely distributed training. Inhibition of PP1 prolongs memory when induced after learning, suggesting that PP1 also promotes forgetting. This property may account for ageing-related cognitive decay, as old mutant animals had preserved memory. Our findings emphasize the physiological importance of PP1 as a suppressor of learning and memory, and as a potential mediator of cognitive decline during ageing.

Aging↗
PubMed1996

CR 2249: a new putative memory enhancer. Behavioural studies on learning and memory in rats and mice.

The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR 2249), a new entity selected from a new series of glutamic acid derivatives, has been investigated in different paradigms for screening nootropics. CR 2249 ameliorated the memory retention deficit produced by scopolamine in step-through-type passive avoidance in rats and by electroconvulsive shock in step-down-type passive avoidance in mice. CR 2249 was also capable of improving performance in behavioural tests of learning and memory in the absence of cholinergic hypofunction or cognitive deficit. The activity was determined using different passive and active avoidance behavioural test procedures on rats. CR 2249 was active only when given 45 min before training and did not show any effect when administered immediately after the learning training or before the retention trial. No changes in the general behaviour or motor activity of the animals were observed, indicating that CR 2249 effects cannot be attributed to sensory-motor deficit. Microdialysis experiments have shown that CR 2249 significantly increased noradrenaline release in the hippocampus of freely moving rats and reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to hypothesize that CR 2249 memory effect might be mediated by a direct or indirect action on noradrenergic transmission. These behavioural results suggest that this new agent has clinical application in memory disorders.

Animals↗
PubMed2005

Perceptual-motor skill learning in Gilles de la Tourette syndrome. Evidence for multiple procedural learning and memory systems.

Procedural learning and memory systems likely comprise several skills that are differentially affected by various illnesses of the central nervous system, suggesting their relative functional independence and reliance on differing neural circuits. Gilles de la Tourette syndrome (GTS) is a movement disorder that involves disturbances in the structure and function of the striatum and related circuitry. Recent studies suggest that patients with GTS are impaired in performance of a probabilistic classification task that putatively involves the acquisition of stimulus-response (S-R)-based habits. Assessing the learning of perceptual-motor skills and probabilistic classification in the same samples of GTS and healthy control subjects may help to determine whether these various forms of procedural (habit) learning rely on the same or differing neuroanatomical substrates and whether those substrates are differentially affected in persons with GTS. Therefore, we assessed perceptual-motor skill learning using the pursuit-rotor and mirror tracing tasks in 50 patients with GTS and 55 control subjects who had previously been compared at learning a task of probabilistic classifications. The GTS subjects did not differ from the control subjects in performance of either the pursuit rotor or mirror-tracing tasks, although they were significantly impaired in the acquisition of a probabilistic classification task. In addition, learning on the perceptual-motor tasks was not correlated with habit learning on the classification task in either the GTS or healthy control subjects. These findings suggest that the differing forms of procedural learning are dissociable both functionally and neuroanatomically. The specific deficits in the probabilistic classification form of habit learning in persons with GTS are likely to be a consequence of disturbances in specific corticostriatal circuits, but not the same circuits that subserve the perceptual-motor form of habit learning.

Adolescent↗
PubMed1995

Dietary alpha-linolenate/linoleate balance influences learning and memory in the senescence-accelerated mouse (SAM).

The senescence-accelerated mouse (SAMP8) is a model of age-related deterioration of memory and learning ability. A semipurified diet supplemented either with safflower oil (rich in linoleate) or with perilla oil (rich in alpha-linolenate) was fed to SAMP8 mouse dams and their pups. The offspring (males from several mothers) at 28 weeks of age were used for behavioral tests. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets. The learning and memory abilities of the two dietary groups were tested with the Sidman active avoidance task and the light and dark discrimination learning test. The group given perilla oil showed much greater improvement in learning in the Sidman active avoidance task than did the group fed safflower oil. In the light and dark discrimination learning test, the total number of responses to positive and negative stimuli was lower in those fed perilla oil, and their responses to positive stimuli were higher than to negative stimuli after the 10th session. Consequently, the correct response ratios of discrimination were higher in the perilla oil group than in the safflower oil group. In the open field test, the total amount of locomotor activity during 5 min was lower in the perilla oil group at 7 months of age than in the group fed safflower oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Verbal learning and memory impairment in adult civilians following penetrating missile wounds.

Verbal memory and learning patterns, as measured by the California Verbal Learning Test (CVLT), following penetrating head injury (PHI) from gunshot wound were studied in 10 acutely injured patients (mean age 25.3 years) at a mean of 2.1 months post-injury. Primary impairment was found on measures of free recall of new verbal information which appeared to be related to deficits in organisational and retrieval functions: (1) the group's learning characteristics were marked by disorganization and an underutilization of active learning strategies; (2) rate of acquisition also appeared to be mildly decreased; (3) nevertheless, the PHI group did not show severe disruption in all aspects of learning and memory. In fact, the group showed a relatively intact capacity to store new information in memory.

Adolescent↗
PubMed2004

Associative learning and memory in a chimpanzee fetus: Learning and long-lasting memory before birth.

We tested whether a chimpanzee fetus could form an association between an extrauterine tone and vibroacoustic stimulation (VAS) using classical conditioning treatment. Two kinds of pure tone were used as the conditioned stimuli, one where a 500-Hz tone was always followed by a VAS of 80 Hz (110 gal), the unconditioned stimulus (US), and another where a 1000-Hz tone was never followed by a VAS. This treatment was repeated 156 times in total until natural labor at 233 days of gestational age. Behavioral tests on the 33rd and 58th days after birth revealed a differential response to the tones: The infant displayed an exaggerated response to the 500-Hz tone, but not to the 1000-Hz tone. Other naïve chimpanzee infants did not show any response to either tone, which suggests that a chimpanzee fetus can distinguish between tones and form an association, and that it retains such information for at least 2 months after birth.

Animals↗
PubMed2004

[Learning and memory].

Memory is broadly divided into declarative and nondeclarative forms of memory. The hippocampus is required for the formation of declarative memories, while a number of other brain regions including the striatum, amygdala and nucleus accumbens are involved in the formation of nondeclarative memories. The formation of all memories require morphological changes of synapses: new ones must be formed or old ones strengthened. These changes are thought to reflect the underlying cellular basis for persistent memories. Considerable advances have occurred over the last decade in our understanding of the molecular bases of how these memories are formed. A key regulator of synaptic plasticity is a signaling pathway that includes the mitogen activated protein (MAP) kinase. As this pathway is required for normal memory and learning, it is not surprising that mutations in members of this pathway lead to disruptions in learning. Neurofibromatosis, Coffin-Lowry syndrome and Rubinstein-Taybi syndrome are three examples of developmental disorders that have mutations in key components of the MAP kinase signaling pathway.

Humans↗
PubMed1978

Cholinergic mechanisms in the learning and memory facilitating effect of the central stimulants. II. Influence of anticholinergic agents on the learning and memory facilitating effect of strychnine.

In experiments involving training of albino rats in a maze it has been found that strychnine (1 mg/kg) introduced 5 min before or immediately after training, improves learning and retention. Upon blocking of the central muscarine-sensitive cholinergic structures (scopolamine 2 mg/kg) and of the nicotine-sensitive structures (spasmolytin 20 mg/kg), the learning and memory facilitating effect of strychnine is not manifested. The realization of the learning and memory facilitating effect of strychnine requires optimum functional level of the activity of the central cholinergic system.

Animals↗
PubMed1991

[A simple multiple maze test to estimate learning and memory in mice: application to the effect of scopolamine on learning and memory].

The apparatus consists of a home cage, a maze cage and a starting box. A maze with four right-middle-left decisions was placed in the maze cage. The starting box was attached and a water tap was placed at an area corresponding to the entrance of the maze. The exit of the maze and the home cage are connected with a tunnel. Food was placed in the home cage. 1) Mice were housed for 10 hr a day in the apparatus and then removed to another cage for fasting. One trial a day was carried out after fasting for more than 12 hr. In each trial, a mouse was put at the starting box, and then the number of errors (entering a blind alley) and the time until the mouse reached the home cage were counted. The mouse passed through the maze with a small number of errors and time. 2) Administration of scopolamine (0.125-0.5 mg/kg, i.p.) to a mouse that had mastered the maze transiently disturbed the maze performance dose-dependently. 3) Mice were housed for 4 hr a day. Scopolamine (0.25 mg/kg, i.p.) was administered either before or after the housing. Scopolamine disturbed the maze performance in the case of both procedures. These results suggest that the method is useful for estimating the memory in mice.

Animals↗
PubMed1996

Sleep stages, memory and learning.

Learning and memory can be impaired by sleep loss during specific vulnerable "windows" for several days after new tasks have been learned. Different types of tasks are differentially vulnerable to the loss of different stages of sleep. Memory required to perform cognitive procedural tasks is affected by the loss of rapid-eye-movement (REM) sleep on the first night after learning occurs and again on the third night after learning. REM-sleep deprivation on the second night after learning does not produce memory deficits. Declarative memory, which is used for the recall of specific facts, is not similarly affected by REM-sleep loss. The learning of procedural motor tasks, including those required in many sports, is impaired by the loss of stage 2 sleep, which occurs primarily in the early hours of the morning. These findings have implications for the academic and athletic performance of students and for anyone whose work involves ongoing learning and demands high standards of performance.

Humans↗
PubMed1978

Cholinergic mechanisms in the learning and memory facilitating effect of the central stimulants. III. Influence of the anticholinergic agents on the learning and memory facilitating effect of amphetamine.

In experiments involving training of albino rats in a maze it has been established that amphetamine in a dose of 0.5 mg/kg introduced 15 min before learning has almost no effect, in a dose of 2 mg/kg it slightly deteriorates learning and retention, while in a dose of 1 mg/kg both learning and retention are markedly improved. However, introduced immediately after training, all three doses tested improve retention upon testing 24 hours and 14 days after training. Upon blocking of the central muscarine-sensitive cholinergic structures (scopolamine 2 mg/kg) and of the nicotine-sensitive structures (spasmolytin 20 mg/kg), the learning and memory facilitating effect of amphetamine is not manifested in the two experimental setups (introduction before and after training). The results resemble the case of independent administration of cholinolytics only, i.e. complete blocking of learning and memory induced by scopolamine and considerable deterioration induced by spasmolytin. The results obtained show that the realization of the learning and retention facilitating effect of amphetamine requires optimum functional level of the activity of the central cholinergic system.

Amphetamine↗
PubMed2005

Genetic approaches to the molecular/neuronal mechanisms underlying learning and memory in the mouse.

Learning and memory is an essential component of human intelligence. To understand its underlying molecular and neuronal mechanisms is currently an extensive focus in the field of cognitive neuroscience. We have employed advanced mouse genetic approaches to analyze the molecular and neuronal bases for learning and memory, and our results showed that brain region-specific genetic manipulations (including transgenic and knockout), inducible/reversible knockout, genetic/chemical kinase inactivation, and neuronal-based genetic approach are very powerful tools for studying the involvements of various molecules or neuronal substrates in the processes of learning and memory. Studies using these techniques may eventually lead to the understanding of how new information is acquired and how learned information is memorized in the brain.

Animals↗
PubMed1996

The estimation of interactions between arginine-vasopressin (AVP) and NMDA receptors in memory and learning processes.

Arginine-vasopressin (AVP) is a neuropeptide which facilitates learning and memory processes. We examinated the participation of NMDA receptors in beneficial effects of peptide. The results of our study show that noncompetitive antagonist of NMDA receptor-MK-801 impairs the effect of AVP on the consolidation of conditioned avoidance responses and antagonist of polyamines site-arcaine reduced advantageous effect of AVP on the retrieval of memory in passive avoidance situation.

2-Amino-5-phosphonovalerate↗
PubMed1995

[Learning and memory].

The ability to learn and to remember increases the adaptability of organisms. The article contains a brief survey of different types of learning and memory and of brain areas of particular importance for these functions. The lessons learnt from patient HM and a personal account of his appearance are given. Finally selected cellular and molecular models for learning and memory in lower and higher animals are briefly reviewed.

Brain↗
PubMed2001

Sleep, memory, and learning.

The relationship of sleep to memory and learning is complex. Sleep affects memory, and memory must be present for learning to occur. A number of studies have been conducted to increase our understanding of their relationship. In addition to the numerous scientific investigations of each concept separately, sleep, memory, and learning have been studied together to determine (a) the effect of sleep on memory and learning, (b) the effect of sleep deprivation in general on memory and learning, (c) the effect of rapid eye movement (REM) sleep deprivation on memory and learning, (d) the effect of memory and learning on REM sleep, and (e) the effect of non-REM sleep loss on memory and learning. Neuroanatomic correlates have been pursued as well with most attention to the hippocampus. Despite considerable efforts to date, many of the studies reveal contradictory or inconclusive findings. Much remains unknown, and additional work is needed. Implications for nursing include those that have a direct effect on the patient, the nurse, and nursing science.

Health Promotion↗
PubMed2003

Heterochronous involvement of neurotrophic factors in the neurochemical organization of learning and memory processes in adult organisms.

Studies were performed on the involvement of neurotrophic factors in the neurochemical mechanisms of the integrative functions of the brain. The effects of various intrahippocampal doses of antibodies to neurotrophic factors--protein S100 and lectin CSL--were studied on the formation, retention, and reproduction of a habituated acoustic startle response and conditioned fear in adult rats. S100b contents in the hippocampus, hypothalamus, frontal cortex, and cerebellar hemispheres and vermis, and in the basal nuclei were measured in rat brains 0.5, 1, 2, 4, 6, 8, 24, and 48 h after long-term habituation to the startle response. Antibodies to neurotrophic factors had selective and dose-dependent effects on the different memory and learning processes underlying these types of behavior. Changes in S100b in brain structures were seen, which were specific in terms of quantitative levels and dynamics, after acquisition of the behavioral habit. The results obtained here, along with previously reported data on the effects of antibodies to S100b and CSL given into the cerebellum, are discussed as experimental support for the hypothesis of the heterochronous neurochemical organization of integrative brain activity.

Analysis of Variance↗
PubMed1997

Visual learning and memory as functions of age.

Age-related changes have been reported for a range of perceptual and cognitive functions. We investigated visual acuity and vernier acuity, as well as visual memory and learning, in four age groups, each comprising 10 subjects and ranging from adolescence to an age group up to 66 years. The groups were matched on general abilities for visuospatial information processing. Visual acuity decreased slightly with increasing age. The reproduction of more complex geometrical material which exceeded short-term memory capacities was significantly impaired in the oldest group relative to young adults. However, vernier acuity thresholds and improvement of thresholds with training did not differ in the four groups. Short-term retention of visual stimuli across 1 or 4 sec was also comparable in the different age groups. Those visual abilities that are limited primarily by cortical, not retinal, factors remained relatively unchanged in our observers despite age-related changes in the eye. Visual memory functions which tap working and long-term memory abilities, on the other hand, showed a significant age-associated decline during adulthood.

Adult↗
PubMed1986

Learning and memory disabilities in young adult rats from mildly zinc deficient dams.

Three experiments were conducted to test the behavior of the offspring of rat dams (ZD) fed a mildly zinc deficient diet (10.0 micrograms Zn/g) during pregnancy and lactation. Since zinc deficiency causes anorexia, a second group of rat dams (PF) was fed the same quantity of the diet during gestation and lactation as was consumed by their ZD mates. A third group of rats (AL) was fed the diet ad lib during gestation and lactation. The PF and AL dams were given zinc supplemented (25.0 micrograms Zn/ml) drinking water whereas the ZD dams were given double distilled, deionized drinking water. After weaning, the offspring of all dams were fed Purina Laboratory Chow ad lib until they were 100 days old. The offspring were then reduced to 85% of their ad lib weight and tested on a 17-arm radial maze for memory and learning. In Experiments 1 and 2, the ZD males suffered a significant learning deficit when compared to the AL males. Whereas the PF males suffered a significant learning impairment in Experiment 1, the learning deficit of the PF group was not as severe as the deficit of the ZD group. There was no impairment in reference (long-term) memory for any of the groups. In Experiment 3, significant differences in working (short-term) memory were found among the three groups of females. The ZD group was significantly inferior in working memory when compared to the PF and AL groups. No significant differences in working memory were found between the PF and AL groups.

Animals↗