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PubMed1997

Psychobiological models of hippocampal function in learning and memory.

We review current computational models of hippocampal function in learning and memory, concentrating on those that make strongest contact with psychological issues and behavioral data. Some models build upon Marr's early theories for modeling hippocampal field CA3's putative role in the fast, temporary storage of episodic memories. Other models focus on hippocampal involvement in incrementally learned associations, such as classical conditioning. More recent efforts have attempted to bring functional interpretations of the hippocampal region in closer contact with underlying anatomy and physiology. In reviewing these psychobiological models, three major themes emerge. First, computational models provide the conceptual glue to bind together data from multiple levels of analysis. Second, models serve as important tools to integrate data from both animal and human studies. Third, previous psychological models that capture important behavioral principles of memory provide an important top-down constraint for developing computational models of the neural bases of these behaviors.

Animals↗
PubMed2007

Circadian-dependent learning and memory enhancement in nociceptin receptor-deficient mice with a novel KUROBOX apparatus using stress-free positive cue task.

Using the novel apparatus KUROBOX, learning and memory behaviors, as well as various parameters of movement activity, were reevaluated in mice deficient for nociceptin/orphanin FQ receptor (NOP-/- mice) or mu-opioid receptor (MOP-/- mice). This method has the advantages that no handling procedures are required throughout the experiments performed over 3 days, positive cue paradigms are used without water or shock stress, and the method does not disturb the nocturnal habit of mice. NOP-/- mice displayed a significant enhancement of learning and memory under stress-free conditions, but there were no changes in the various physical and psychological parameters of movement activity (nest stay ratio, distance moved, speed and angle in the movement) and biological rhythm that were measured. Enhancement of nocturnal learning was observed during the first 12-h dark cycle, and enhancement of memory was observed at the beginning of the second dark cycle in NOP-/- mice. In contrast, MOP-/- mice showed no significant change in learning and memory behaviors or in physical and psychological parameters of movement activity, except for speed, MOP-/- mice showed a significant decrease in speed of movement. Thus, the KUROBOX apparatus provides a useful alternative method to evaluate learning and memory activity under the more physiological conditions. In addition, this apparatus has an advantage that various physical and psychological parameters of movement activity affecting learning and memory behavior are also evaluated at the same time.

Animals↗
PubMed2006

Effects of Yizhi Capsule on learning and memory disorder and beta-amyloid peptide induced neurotoxicity in rats.

OBJECTIVE: To explore the effects of Yizhi Capsule (YZC) on learning and memory disorder and beta-amyloid peptide induced neurotoxicity in rats. METHODS: Various doses of YZC were administered to Sprague-Dawley (SD) rats for 8 consecutive days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Besides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after beta amyloid peptide(25 - 35) (Abeta(25 - 35)) intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant. RESULTS: Compared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test, as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Abeta(25 - 35) intoxicated neurons and reduce the LDH contents in cultured supernatant. CONCLUSION: YZC has an action of improving learning and memory disorder, and good protective effect on Abeta(25 - 35) induced neurotoxicity in SD rats.

Alpinia↗
PubMed1989

Preserved learning and memory in amnesia: intact adaptation-level effects and learning of stereoscopic depth.

Amnesic patients and control Ss performed similarly on 2 memory tests. In Experiments 1A and 1B, amnesic patients exhibited intact adaptation-level effects: An experience lifting and judging a group of weights influenced their judgments of a 2nd group of weights 20-25 min later. The effect did not depend on peripheral accommodation, because Ss used 1 hand during their 1st encounter with the weights and the opposite hand during their 2nd encounter. In Experiment 2, amnesic patients acquired at a normal rate the ability to perceive binocular depth using random-dot stereograms. In both experiments, amnesic patients benefited from recent experience, despite the fact that they could not remember their prior experience accurately. The preserved memory abilities demonstrated here appear to be examples of implicit, or nondeclarative, memory.

Adaptation, Psychological↗
PubMed2006

[Participation of endogenous brain histamine on learning and memory].

It is well known that histamines play an important role as a neurotransmitter in the central nervous system and participate in several physiological functions, such as the regulation of body temperature, food intake, circadian rhythm and analgesia. Since the first report by de Almeida and Izquierdo that histamines facilitate memory performance in mice, it has been revealed that the histaminergic nervous system in the brain plays a crucial role in learning and memory functions. First, we demonstrate the effects of histamines and histaminergic drugs on learning and memory using active avoidance and 8-arm radial maze tests. Many reports suggest that acetylcholine and N-methyl-D-aspartate (NMDA) receptors play an important role in learning and memory. In this report, we also describe the interaction between histamine-induced memory facilitation and acetylcholine or NMDA receptors.

Animals↗
PubMed1994

[Long term potentiation of the synaptic efficacy: mechanisms, functional properties and role in learning and memory].

It is widely assumed that information is stored in the brain as changes in the efficacy of synaptic connections on those neurons which are activated during learning. In the past decade, long-term potentiation (LTP) of synaptic efficacy has become the dominant model in the search for the cellular bases of learning and memory. Today, considerable progress has been made in understanding the synaptic events underlying LTP and in identifying the neural systems which express LTP. In parallel, the hypothesis that the mechanisms underlying LTP are activated during learning and actually serve learning and memory has gained much empirical support. This article summarizes present knowledge about the properties and mechanisms of LTP and reviews the major experimental strategies that have been pursued to elucidate its functional significance in learning and memory. The data provide a working framework within which the dynamics of cellular mechanisms of learning and memory is profiled.

Animals↗
PubMed2003

Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice.

Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Flame retardants are used to suppress or inhibit combustion processes in an effort to reduce the risk of fire. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), are present and increasing in the environment and in human milk. The present study shows that neonatal exposure to 2,2',4,4',5,5'-hexaBDE (PBDE 153), a PBDE persistent both in environment and in human milk, can induce developmental neurotoxic effects, such as changes in spontaneous behaviour (hyperactivity), impairments in learning and memory, and reduced amounts of nicotinic receptors, effects that get worse with age. Neonatal NMRI male mice were orally exposed on day 10 to 0.45, 0.9, or 9.0 mg of PBDE 153/kg of body weight. Spontaneous behaviour (locomotion, rearing, and total activity) was observed in 2-, 4-, and 6-month-old mice, Morris water maze at an age of 6 months. The behaviour tests showed that the effects were dose-response and time-response related. Animals showing defects in learning and memory also showed significantly reduced amounts of nicotinic receptors in hippocampus, using alpha-bungarotoxin binding assay. The observed developmental neurotoxic effects seen for PBDE 153 are similar to those seen for PBDE 99 and for certain PCBs. Furthermore, PBDEs appear to as potent as the PCBs.

Administration, Oral↗
PubMed2004

Nicotine improves learning and memory in rats: morphological evidence for acetylcholine involvement.

It has been suggested that nicotine improves rapid information processing (learning and memory) tasks. However, it is not clear which aspects of cognition actually underlie these improvements because relatively less attention has been given to nicotinic cholinergic systems compared to muscarinic systems. The authors therefore studied the effects of nicotine on the learning and memory performance by a step-through passive avoidance task. Nicotine (0.4 mg/kg) was administered s.c. single dose (acute group), once a day for 3 days (subchronic group) or 21 days (chronic group). Nicotine treated and control rats were trained in one trial learning step-through passive avoidance task, where retention latencies were carried out 1 h, 24 h, and 3 days after learning trial. Treatment with nicotine before training session prolonged the latencies significantly (p < .01). Control group, acute, subacute and chronic nicotine treatment groups showed latencies 4.75 +/- 0.6, 69.4 +/- 14, 116.2 +/- 30, and 118.5 +/- 23 s, respectively. In addition, to prove the actual contribution of nicotinic cholinergic system in improvement of learning and memory processing, histological methods that permit the visualization and quantification of ACh levels were used. Electron microscopic evaluation revealed increased numbers of Ach-containing vesicles especially in hippocampus in chronic nicotine-treated rats; although frontal and temporal cortex in addition to hippocampus showed increment in Ach vesicles in a lesser extent in all nicotine treatment groups. These results indicate that long-term nicotine treatment can be important for improving cognitive function in regard to increased cholinergic activity.

Acetylcholine↗
PubMed1995

Acetylcholine: a neurotransmitter for learning and memory?

The cholinergic hypothesis claims that the decline in cognitive functions in dementia is predominantly related to a decrease in cholinergic neurotransmission. This hypothesis has led to great interest in the putative involvement of the cholinergic neurotransmission in learning and memory processes. This review aims to assess the data of studies in which the role of acetylcholine (ACh) in cognitive functions was investigated. For this purpose, studies from three different fields of research, namely: (1) behavioral pharmacology (effects of drugs on behavior); (2) behavioral neuroscience (effects of brain lesions on behavior); and (3) dementia, are discussed separately. The experimental tools that have been used in pharmacological studies may appear to be inadequate to enable conclusions to be drawn about the involvement of ACh in learning and memory processes. Especially, the use of scopolamine as a pharmacological tool is criticized. In the field of behavioral neuroscience a highly specific cholinergic toxin has been developed. It appears that the greater and more specific the cholinergic damage, the fewer effects can be observed at the behavioral level. The correlation between the decrease in cholinergic markers and the cognitive decline in dementia may not be as clearcut as has been assumed. The involvement of other neurotransmitter systems in cognitive functions is briefly discussed. Taking into account the results of the different fields of research, the notion that ACh plays a pivotal role in learning and memory processes seems to be overstated. Even when the role of other neurotransmitter systems in learning and memory is taken into consideration, it is unlikely that ACh has a specific role in these processes. On basis of the available data, ACh seems to be more specifically involved in attentional processes than in learning and memory processes.

Acetylcholine↗
PubMed2003

Associative learning and memory in Drosophila: beyond olfactory conditioning.

The associative learning abilities of the fruit fly, Drosophila melanogaster, have been demonstrated in both classical and operant conditioning paradigms. Efforts to identify the neural pathways and cellular mechanisms of learning have focused largely on olfactory classical conditioning. Results derived from various genetic and molecular manipulations provide considerable evidence that this form of associative learning depends critically on neural activity and cAMP signaling in brain neuropil structures called mushroom bodies. Three other behavioral learning paradigms in Drosophila serve as the main subject of this review. These are (1) visual and motor learning of flies tethered in a flight simulator, (2) a form of spatial learning that is independent of visual and olfactory cues, and (3) experience-dependent changes in male courtship behavior. The present evidence suggests that at least some of these modes of learning are independent of mushroom bodies. Applying targeted genetic manipulations to these behavioral paradigms should allow for a more comprehensive understanding of neural mechanisms responsible for diverse forms of associative learning and memory.

Journal Article↗
PubMed1995

Spatial learning and memory as a function of age in the dog.

Spatial learning and memory were studied in dogs of varying ages and sources. Compared to young dogs, a significantly higher proportion of aged dogs could not acquire a spatial delayed nonmatching-to-sample task. A regression analysis revealed a significant age effect during acquisition. Spatial memory was studied by comparing performance at delay interval of 20, 70, and 110 s. At short delays aged and young dogs were similar; at longer delays, errors increased to a greater extent in old than in young dogs; however this was not statistically significant. It was possible to identify 2 groups of aged animals, age-impaired and age-unimpaired. Several of the dogs were also tested on an object recognition memory task, which was more difficult to learn than the spatial task. The possibility that these findings are confounded by breed differences is considered. Overall, the present results provide further evidence of the value of a canine model of aging.

Aging↗
PubMed2002

Early postnatal protein malnutrition affects learning and memory in the distal but not in the proximal cue version of the Morris water maze.

Learning and memory of early postnatal protein malnourished rats were investigated in the Morris water maze. During the lactation period (21 days) each litter (mother plus six male and two female pups) was provided with 16% (well-nourished) or 6% (malnourished) protein diets. After weaning, rats remained on the same diet until 49 days of age. From day 50 on all animals were fed a commercial lab chow. Experiments started on day 70. In experiment I (proximal cue version) the animals were trained to escape from water to a visible platform (3 cm above the water level) in six trials daily for four consecutive days, completing 24 trials. In experiment II (distal cue version) the animals were trained to escape from water to a submerged platform using the same procedure as in experiment II. After the 24th trial, the platform was removed and the animals were submitted to a 60-s trial (probe trial). Seven and twenty-eight days after training, the retention test was conducted in one 180-s trial. The results showed no impairment of the learning or memory of malnourished animals tested in the proximal cue version but an increased latency and distance traveled to find the submerged platform in the distal cue version of the procedure. In the distal cue version the malnourished animals also showed increased latency to find the platform 7 and 28 days after the test training. No difference due to diet was found in the probe trial test indicating that, once the task is acquired, malnourished rats can manage extra-maze cues as easily as well-nourished rats. It is suggested that the present results can be due to alterations produced by protein malnutrition in the hippocampal formation or also to reflect the higher emotionality of rats following early malnutrition, specially considering the fact that postnatally malnourished animals are more reactive to unpleasant or aversive stimuli as cold water.

Animals↗
PubMed2004

Strains of rodents and the pharmacology of learning and memory.

Mendelian genetic tools have extensively been used to improve the description of the pharmacological mechanisms involved in learning and memory. The first part of this short review describes experiments involving the bidirectional selection of rats or mice for extreme behavioral characteristics or for sensitivity to pharmacological treatments. The second part focuses specifically on in-breeding. In conclusion, the advantages and the limits of a Mendelian pharmacogenetic approach of learning and memory are discussed.

Animals↗
PubMed2004

The physiology of learning and memory: role of peptides and stress.

The neuropeptides, as well as their respective receptors, are widely distributed throughout the mammalian central nervous system. During learning and memory processes, besides structural synaptic remodeling, changes are observed at molecular and metabolic levels with the alterations in neurotransmitter and neuropeptide synthesis and release. While there is consensus that brain cholinergic neurotransmission plays a critical role in the processes related to learning and memory, it is also well known that these functions are influenced by a tremendous number of neuropeptides and non-peptide molecules. Arginine vasopressin (AVP), oxytocin, angiotensin II, insulin, growth factors, serotonin (5-HT), melanin concentrating hormone, histamine, bombesin and gastrin-releasing peptide (GRP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), dopamine, corticotropin releasing factor (CRF) have modulatory effects on learning and memory. Among these peptides CCK, 5-HT and CRF play strategic roles in the modulation of memory processes under stressful conditions. CRF is accepted as the main neuropeptide involved in both physical and emotional stress, with a protective role during stress, possibly through the activation of the hypothalamo-pitiuitary (HPA) axis. The peptide CCK has been proposed to facilitate memory processing and CCK-like immunoreactivity in the hypothalamus was observed upon stress exposure, suggesting that CCK may participate in the central control of stress response and stress-induced memory dysfunction. On the other hand, 5-HT appears to play a role in behaviors that involve a high cognitive demand and stress exposure activates serotonergic systems in a variety of brain regions. The physiological role and therapeutic efficacy of various neuropeptides and the impact of stress exposure in the acquisition and consolidation of memory will be reviewed thoroughly.

Animals↗
PubMed2006

[Effects of Naohuandan Recipe on learning and memory abilities of SAM-P/8 mice and its role in anti-oxidation and anti-apoptosis].

OBJECTIVE: To investigate the effects of Naohuandan Recipe on learning and memory abilities of SAM-P/8 mice and its role in anti-oxidation and anti-apoptosis. METHODS: Forty SAM-P/8 mice were randomly divided into four groups, which were untreated (normal saline-treated) group, Yinkeluo Tablets (extracts of gingko leaf)-treated group, low-dose Naohuandan Recipe-treated group and high-dose Naohuandan Recipe-treated group. Mice in these groups were given corresponding drugs orally for 105 days. Then the performances of learning and memory of mice were tested by a step-down passive avoidance task and a Y-maze test. The serum levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were detected. The expression level of bcl-xl mRNA in cerebral cortex and hippocampus of mice was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The performances of learning and memory in the Yinkeluo Tablets-treated group, low- and high-dose Naohuandan Recipe-treated groups were significantly improved as compared with those in the untreated group (P<0.05 or P<0.01), and such performance was the best in the high-dose Naohuandan Recipe-treated group among these four groups (P<0.01). The serum levels of SOD and GSH-Px and the expression of bcl-xl mRNA in cerebral cortex and hippocampus of mice in the Yinkeluo Tablets-treated group, low- and high-dose Naohuandan Recipe-treated groups were also significantly higher than those in the untreated group (P<0.05 or P<0.01), while the serum level of MDA in the untreated group was higher than that in the other three groups (P<0.01). CONCLUSION: Naohuandan Recipe can improve learning and memory abilities of SAM-P/8 mice, and this effect may be related to its anti-oxidation efficacy and enhancement of expression level of bcl-xl mRNA.

Aging↗
PubMed2004

[Effects of febrile seizures on motor, behavior, spatial learning and memory in rats].

OBJECTIVE: Febrile seizure is a very common emergency in children. Although researchers home and abroad constantly pay close attention to studies on brain damage and lesion possibly caused by febrile seizure, studies of effects on motor, behavior, spatial learning and memory are relatively seldom. In our study, Sprague-Dawley rats were utilized for the purpose of the exploration of effects of febrile seizures on their motor, behavior, spatial learning and memory. METHODS: Sixty 21-day-old male Sprague-Dawley rats, weighing (50 +/- 5) g were divided randomly and equally into febrile seizure group (FS), febrile control group (FG) and normal control group (NG). Febrile seizure animal model was induced by hyperthermal bath with 45 degrees C water. Febrile seizure was induced twice a day, thus ten times within five days in FS group. Rats of FG group were immersed in the same hyperthermal water for 2 minutes. Nothing special was performed on NG group. The abilities of motor and behavior of every rat in these 3 groups were tested in inclined plane test (IPT), overhanging test (OHT) and open field test (OFT) to show their varieties. Furthermore, Morris water maze was applied to evaluate the effects by febrile seizure on spatial learning and memory in rats during the place navigation test and spatial probe test. RESULTS: In the present experiments, febrile seizures were altogether induced 192 times with the mean latency being (4.25 +/- 0.98) minutes and the mean duration being (1.06 +/- 0.59) minutes. The experiments confirmed that multiple febrile seizures could lead to decreases of abilities in all tests in which analysis of variance indicated that there were significant differences between febrile seizure group and the other two (P < 0.01). In inclined plane test, the turning ability of the rats was weakened. The mean turning time was (9.1 +/- 2.6) seconds for FS, (5.3 +/- 2.1) seconds for FG and (5.3 +/- 2.0) seconds for NG. In overhanging test, the overhanging time was shortened: (33.4 +/- 18.1) seconds for FS, (50.1 +/- 20.3) seconds for FG and (59.0 +/- 20.7) seconds for NG. In the open field test, the rats became less active with the scores (5.1 +/- 2.0) for FS, (10.4 +/- 3.0) for FG and (13.2 +/- 2.3) for NG. Meanwhile, the authors discovered the decreases of the abilities of spatial learning and memory in rats caused by febrile seizures many times. In the place navigation test, the mean escape latency for the rats' looking for hidden platform was prolonged; the efficiency of their search strategy decreased; the swimming time the animals spent in platform region decreased [(44.02 +/- 5.25) seconds for FS, (51.75 +/- 5.28) seconds for FG and (57.07 +/- 5.36) seconds for NG; analysis of variance, P < 0.01.]; the number of times they crossed the platform area decreased [(6.07 +/- 1.77) times for FS, (9.25 +/- 2.07) times for FG and (11.34 +/- 2.37) times for NG; analysis of variance, P < 0.01]; the percentage of their swimming time fell (36.68% for FS, 43.13% for FG and 47.56% for NG). CONCLUSION: The experiments confirmed that multiple febrile seizures could result in damage and lesion of motor, behavior, spatial learning and memory in rats.

Animals↗
PubMed1995

[Genes and the modulation of learning and memory].

Recently, progress in the study of the relationship between gene and the modulation of learning and memory was noticeable. The studies showed that: (1) The expression of immediate early genes (IEGs), especially the c-fos, is a necessary prerequisite for the formation of memory; the induction of long term potentiation (LTP) is accompanied by an increase of IEGs expression; (2) Mice with deficiency of alpha-Calcium-Calmodulin Kinase II (alpha-CaMK II), or neural-cell adhesion molecules (N-CAM) or tyrosine kinase gene (fyn) generated by gene targeting appear deficits in spatial learning and memory, mutation of alpha-CaMK II and N-CAM gene can also interfere with the induction and maintenance of LTP; (3) The single-gene mutants of Drosophilia (dnc, rut) showed significant decrease of the ability of memory. The mechanism is related to the altered synaptic plasticity, and the mushroom body may be the memory center of Drosophila.

Animals↗
PubMed2004

Proof of the mysterious efficacy of ginseng: basic and clinical trials: effects of red ginseng on learning and memory deficits in an animal model of amnesia.

Ameliorating effects of red ginseng on learning and memory deficits due to hippocampal lesions and aging were reviewed; the performance of young rats with selective hippocampal lesions with or without red ginseng (p.o.), and aged rats with or without red ginseng (p.o.) in the spatial learning tasks was compared with that of sham-operated or intact young rats. Each rat was tested with 3 types of spatial learning tasks (distance movement task, DMT; random reward place search task, RRPST; and place learning task, PLT) in a circular open field using intracranial self-stimulation (ICSS) as reward. The results in the DMT and RRPST indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng and aged rats with and without ginseng were not significantly different from that of control young rats. However, young rats with hippocampal lesions without ginseng and aged rats without ginseng displayed significant deficits in the PLT. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions in the PLT. Similarly, red ginseng improved performance of aged rats in the PLT. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous system, partly through effects on the hippocampal formation. However, its mechanisms are still unclear, and further studies are required.

Aging↗