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Testosterone and photoperiod interact to affect spatial learning and memory in adult male white-footed mice (Peromyscus leucopus).

Gonadal hormones affect spatial learning and memory in mammals and circulating gonadal hormone concentrations fluctuate by season. Most nontropical rodents are spring/summer breeders and males display higher testosterone concentrations during the breeding season compared with the nonbreeding season (fall/winter). Seasonal patterns of testosterone concentration (as well as many other seasonal modifications of physiology, morphology, and behaviour) are induced by manipulation of photoperiod (day length; i.e. short or long days) in the laboratory. Coincident with reducing testosterone concentration, short days also impair spatial learning and memory performance in male white-footed mice (Peromyscus leucopus) compared with long days. We hypothesized that short-day-induced reduction of testosterone concentrations inhibits spatial learning and memory performance compared with long days. Adult male white-footed mice were maintained in long (16 h light/day) or short (8 h light/day) days for 14 weeks following sham-castration, castration plus saline implant, or castration plus testosterone implant treatment. Spatial learning and memory was assessed using a water maze, and photoperiod-evoked changes in gene expression of sex steroid receptors within the hippocampus were also examined. Castrated, short-day mice with testosterone replacement displayed enhanced water maze performance compared with other short-day mice, but no differences among testosterone treatments were observed in long-day mice. Photoperiod did not affect hippocampal androgen, oestrogen alpha, or oestrogen beta receptor gene expression. These results suggest that photoperiod modulates the effects of testosterone on spatial learning performance by mechanisms indirect of the hippocampus.

Animals↗

Behavioral performance of tfm mice supports the beneficial role of androgen receptors in spatial learning and memory.

In adulthood, androgens and androgen receptors might contribute to the sexually dimorphic performance in spatial learning and memory, but their roles seem complex. To study the potential role of androgen receptors in spatial learning and memory, we tested adult 6-8-month-old mutant mice with a naturally occurring defect in the androgen receptor gene (testicular feminization mutant or tfm) and C57Bl/6J wild-type mice. Because the trait is X-linked, only tfm males are completely androgen insensitive while female tfm mice are heterozygous, carrying one wild-type and one tfm copy of the androgen receptor. Here we show that female tfm carrier mice outperform tfm male mice in the water maze, while there are no gender differences in water maze performance in wild-type mice. In tfm mice, there were no gender differences in measures of anxiety in the open field or plus maze or sensorimotor function, indicating that potential differences in these measures did not contribute to the differences observed in the water maze. There were no differences in tfm and wild-type female and male mice in emotional learning and memory in the passive avoidance test. These findings support a beneficial role for androgen receptors in spatial learning and memory.

Androgen-Insensitivity Syndrome↗

On the role of the hippocampus in learning and memory in the rat.

An overview of lesion experiments concerned with the involvement of the hippocampus in learning and memory in the rat is presented. Multiple injections of small amounts of ibotenic acid were used to selectively remove the hippocampus (dentate gyrus, hilar cells, CA1-CA3 pyramidal cells). Similar selective, axon-sparing ibotenate lesions of hippocampus were used in a series of learning and memory experiments employing tasks that are thought to be important in hippocampal function. The performance of rats with the hippocampus removed was compared with that of control animals in the acquisition and retention of spatial versus nonspatial information, forgetting of spatial and nonspatial information, contextual learning, recognition memory and concurrent discrimination learning, and complex representational learning (conditional discrimination and negative patterning learning). The general finding that rats without a hippocampus were impaired on those tasks that required the utilization of spatial and contextual information stands in contrast with the spared performance that was found in learning about and handling (even complex) nonspatial information. Rather than support for views that emphasize a role for the hippocampus in specific memory processes (working memory, declarative memory, temporary memory buffer, configural learning), the present results are more compatible with the idea that the hippocampus plays an especially important role in processing and remembering spatial and contextual information. The limited data that are available using more selective lesions of related hippocampal formation structures (entorhinal cortex, subiculum) suggest that these structures also make important contributions to learning and memory, and that some of these contributions may be different from those made by the hippocampus.

Animals↗

Characterization of neuropeptide Y, Y(2) receptor knockout mice in two animal models of learning and memory processing.

Neuropeptide Y (NPY) and, in particular, the Y2 receptor subtype, has been suggested to be involved in learning and memory processing. However, the precise role of Y2 receptors in learning and memory remains unclear. In the present study, mice lacking NPY Y2-type receptors were assessed in two animal models of learning and memory processing. We found that NPY Y2-/- mice displayed a deficit on the probe trial in the Morris water maze task, whereas acquisition performance, swim speed, and visible platform performance did not differ significantly between groups. In addition, NPY Y2-/- mice exhibited a marked deterioration in object memory 6 h, but not 1 h, following initial exposure in the object recognition test. Both groups of mice showed similar locomotor activity profiles in a low-stress, open field test. These data support the hypothesis that Y2 receptors are involved in the regulation of learning and memory processing.

Animals↗

[Effects of different light-dark cycle on learning and memory in mice].

OBJECTIVE: To study the effect of different light-dark cycles on learning and memory in mice. METHOD: Seventy-two ICR mice were raised under different light-dark cycles including LD 5h/5h, LD 12h/12h and LD 22h/22h for 6 weeks. The locomotor activity was recorded continuously. Morris water-maze task was used as the judging criteria for spatial learning and memory. RESULT: The locomotor activity rhythm was consistent with the light-dark cycle. The period of light-dark cycle shorter than 24 h such as 10 h could effect on the ability of learning and memory in mice. CONCLUSION: The short period of light-dark cycle can improve the ability of learning and memory in mice.

Animals↗

Effects of lobeline, a nicotinic receptor agonist, on learning and memory.

The effects of (-)-lobeline were assessed in two learning and memory tasks in which nicotine-induced enhancement of performance has previously been demonstrated. Lobeline (19 mumol/kg, IP) administered immediately after inhibitory (passive) avoidance training improved retention performance assessed 24 h later, as rats that received this dose of lobeline took significantly longer to enter the shock compartment on the test day than rats that had been treated with vehicle. Pretraining lobeline treatment (1.9 mumol/kg, IP) significantly improved performance of rats with septal lesions in a spatial discrimination water maze, a finding confirmed when rats were retrained using new spatial locations and vehicle and lobeline treatments were reversed in a crossover design. The effective dose of lobeline in the inhibitory avoidance task was about 10-fold higher than that generally reported for nicotine, and direct comparison of the suppression of locomotor activity shortly after administration of nicotine or lobeline also revealed a 10-fold greater potency for nicotine. In contrast, no difference was found between the effective dose of lobeline in the current study and that we previously found with nicotine in the water maze. These findings suggest that lobeline's effects on the performance of learning and memory tasks may be similar to those of nicotine. Coupled with previous reports that lobeline does not produce the nicotine cue in drug discrimination experiments, this study also suggests that nicotinic receptors involved in the modulation of memory processes may be distinct from those involved in producing the nicotine cue.

Animals↗

[Learning and memory processes during postnatal ontogenesis in rats with spontaneous hypertension].

The examination of learning and memory processes by a conditional reflectory locomotor avoidance reaction on 8-, 10-, 12-, 14-, 16-, 20-, 26-, and 50-week-old rats with spontaneous hypertension (SHR Okamoto/Aoki) revealed, up to an age of 20 weeks, correlations between the height of blood pressure and learning and memory performance by analogy with parameters of the hydrocarbon metabolism [1,2]. Three stages were observed: Stage I: Juvenile animals (8--10 weeks) with mean systolic blood pressure values of 150 to 170 torr showed a comparatively low restriction of learning and memory processes. Stage II: In adult animals (12--20 weeks) with mean systolic blood pressure values of 180 to 210 torr learning was inhibited by about 50%, while retention of memory was completely disturbed. Stage III: In old animals (26--50 weeks) with mean systolic blood pressure values above 200 torr the faculty to learn a conditional avoidance reflex was virtually lost. Destruction or blockage of hypothalamic behavioral substances are assumed to cause the derangement of learning and memory processes in spontaneously hypertensive rats.

Aging↗

Genetic dissection of learning and memory in mice.

In this minireview, we discuss different strategies to dissect genetically the keystones of learning and memory. First, we broadly sketch the neurogenetic analysis of complex traits in mice. We then discuss two general strategies to find genes affecting learning and memory: candidate gene studies and whole genome searches. Next, we briefly review more recently developed techniques, such as microarrays and RNA interference. In addition, we focus on gene-environment interactions and endophenotypes. All sections are illustrated with examples from the learning and memory field, including a table summarizing the latest information about genes that have been shown to have effects on learning and memory.

Animals↗

Protective effect of Ginkgo biloba leaf extract on learning and memory deficit induced by aluminum in model rats.

OBJECTIVE: To examine the protective effect of Ginkgo biloba leaf extract (GbE) on learning and memory deficit induced by aluminum chloride (AlCl(3)), and explore its mechanisms. METHODS: The rat models with learning and memory deficit were induced by administering via gastrogavage and drinking of AlCl(3) solution. And the model rats were treated with GbE at the dose of 50, 100, 200 mg/kg every day for 2 months accompanied with drinking of AlCl(3) solution, respectively. Their abilities of spatial learning and memory were tested by Morris water maze, and the acetylcholinesterase (AChE) activity in serum was assayed with chemical method, the AChE expression in hippocampus was observed by immunohistochemistry assay, and then quantitative analysis was done by BI 2000 image analysis system. RESULTS: Learning and memory deficit of rats could be induced by AlCl(3) solution (P < 0.01), and AChE expressions in rats hippocampus were increased (P < 0.01); GbE ameliorated learning and memory deficit and reduced AChE expression in rats hippocampus in a dose-dependent manner, while GbE significantly increased serum AChE activity at the dose of 200 mg/kg each day (P < 0.05). CONCLUSION: GbE can ameliorate learning and memory deficit induced by AlCl(3), which may be due to its inhibition of the AChE expression in hippocampus.

Acetylcholinesterase↗

[Clinical and experimental studies of jianyi oral liquid in improving learning and memory of the aged].

The effect of Jianyi oral liquid (JYOL) in improving learning and memory of the aged was investigated in this study. The results showed that the learning and memory of the aged subjects and mice was improved after taking JYOL, the level of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), cyclic adenosine monophosphate (cAMP) in plasma of aged subjects and brain of aged mice and the content of superoxide dismutase (SOD) in red blood cells of both aged person and mice were significantly higher than those of premedication or control respectively. It was considered that the mechanism of the effect of JYOL in improving learning and memory might related to enhance the brain activity and the capability of clearing free radicals by increasing monoamines, cAMP and SOD of the aged body.

Aged↗

Age-related decline in water maze learning and memory in rats: strain differences.

Rats display an age-related impairment in learning and memory; however, few studies have systematically examined this relationship in multiple strains. The present study used a repeated acquisition water maze task to test the hypothesis that age-related decreases in learning and memory occur at different rates in three strains of rats, i.e. Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats. All three strains of rats displayed age-related decreases in spatial learning and memory; however, the rate of decline differed between the strains. Compared to young rats of the same strain, only SHR were significantly impaired at 12 months of age. All three strains displayed moderate impairment in learning the task at 18 months of age, and at 24 months of age all three strains of rats were severely impaired in the task, but SD performed best at 18 and 24 months of age. Further, SD and SHR displayed a probe trial bias at 3 months of age, but only SD had a bias at 12 months of age and none of the rats showed the bias at later ages. Thus, in these three strains, age-related impairment of spatial memory proceeds at different rates.

Aging↗

The role of neuropeptides in learning and memory: possible mechanisms.

Endogenous neuropeptides such as vasopressin, adrenocorticotropin and opioids have significant effects on learning and memory. However, because of the complexity of behaviour, that is defined as 'learning' and 'memory' and, because of the limitation of current knowledge, it has been difficult to interpret these behavioural data, especially via neural mechanisms. The application of modern experimental techniques including molecular biology such as cloning and electrophysiology, such as patch-clamp, has had a significant impact upon the concepts about drugs, including neuropeptides action sites. This allows us to try to interpret some behavioural consequences influenced by neuropeptides. The data on effects of some neuropeptides on behaviours and their possible mechanisms are reviewed. Whatever the mechanisms, vasopressin, adrenocorticotropic hormone and endogenous opioids seem to have important effects upon learning and memory and these open up the possibility that drugs enhance cognitive functions or treat dementia via alteration of functions of neuropeptides. Some criteria are proposed for evaluating the validity of behavioural tests for neuropeptides.

Adrenocorticotropic Hormone↗

Learning and memory in combat veterans with posttraumatic stress disorder.

OBJECTIVE: The authors investigated a broad range of memory functions for stimuli unrelated to trauma to determine whether symptoms such as intrusive memories might reflect an underlying cognitive deficit unrelated to the psychological content of the traumatic memory in patients with posttraumatic stress disorder (PTSD). METHOD: The authors measured the intellectual functioning of 20 male combat veterans with PTSD and 12 normal comparison subjects using the WAIS and evaluated them for performance on memory using the California Verbal Learning Test. RESULTS: Veterans with PTSD showed normal abilities in the functions of initial attention, immediate memory, cumulative learning, and active interference from previous learning. However, these veterans showed a circumscribed cognitive deficit, manifested by the presence of substantial retroactive interference and revealed by a significant decrement in retention following exposure to an intervening word list. CONCLUSIONS: The data suggest that patients with PTSD may have fairly specific deficits in the monitoring and regulation of memory information.

Adult↗

Learning and memory in young and aged Fischer 344 rats.

Changes in learning and memory processes that occur with senescence were investigated in male and female Fischer 344 rats, 3-26 mth of age. Age-related impairments were seen in retention of inhibitory avoidance learning, acquisition of a Y-maze discrimination task, and in a swim escape task with short intertrial training intervals. In contrast, old animals performed better than the young rats in an active avoidance task. No age differences were observed in either open field activity or in flinch or jump thresholds to footshock. These results indicate that impairments in learning and memory processes of aged rats are task-specific, and that memory deficits in old rats are best seen following one-time-only events or with weak training. The behavioral baselines described will help in the design of further research to correlate memory and neurobiological changes observed during the aging process in the rat.

Aging↗

Accelerated senescence prone mouse-8 shows early onset of deficits in spatial learning and memory in the radial six-arm water maze.

Available data indicate that the senescence-accelerated prone mouse 8 (SAMP8) is an appropriate model of brain aging, with impairments in nonspatial learning and memory beginning as early as 2 months of age, and spatial learning and memory deficiencies not becoming apparent until after 4 months of age. However, with other strains (e.g., C57BL mice), the impairment in spatial memory was found earlier than that in nonspatial memory. We considered the possibility that the observed differences could be due to strain-specific differences in the training equipment. In the present study, a new optimized testing apparatus-the radial six-arm water maze (RAWM)-for detecting spatial learning and memory in mice, was employed, to determine whether there is impairment of spatial learning and memory in young SAMP8. The relationship between the spatial learning measures observed with the RAWM and the Morris maze, a classic spatial learning and memory testing apparatus, was also explored. It was found that, in the RAWM, rather than in the Morris maze, the impairment in spatial learning could be measured in SAMP8 mice as early as 3 months old, and the impairment in spatial memory in SAMP8 mice aged 5 months. These results suggested that the spatial learning and memory deficiencies could be found in early life of SAMP8 mice, and that RAWM and Morris maze each detect different aspects of spatial learning and memory.

Aging↗

[Learning and memory].

INTRODUCTION: The paper briefly reviews current knowledge on learning and memory processes, considered at the behavioral, cognitive and neural levels. DEVELOPMENT: After establishing the distinction between different learning processes (behavioral learning, skill acquisition and information acquisition processes), the specific learning phenomena belonging to each of these varieties are analyzed. Associative learning is described as a behavioral (pavlovian conditioning and instrumental learning) and cognitive (predictive learning and categorization) process. Also described are the properties of perceptual and motor learning, as those of the processes by which cognitive skills (e.g., rule learning) are acquired. Then, the distinction between short-term and long-term memory is discussed, referring to short-term memory as a working memory system that assists the performance of a variety of thinking and reasoning tasks. Finally, the two main long-term memory theories are discussed, considering the semantic/episodic and implicit/explicit memory dichotomies.

Animals↗

Effect of antisense oligonucleotide of noggin on spatial learning and memory of rats.

AIM: To investigate the effect of antisense oligonucleotide (ASODN) of noggin on rat spatial learning and memory. METHODS: Expression of noggin mRNA was measured by in situ hybridization method and the ability to spatial learning and memory was tested with Morris water maze. RESULTS: Compared with control rats, noggin mRNA positive neurons in dentate gyrus (DG) and CA3 region of hippocampus were markedly increased after the Morris water maze training (P<0.01). The increase of noggin mRNA positive neurons in hippocampus following maze training could be significantly blocked by icv injection of antisense noggin ODN, and the injection also impaired the learning and memory formation as compared to that in control rats. But the sense oligonucleotide (SODN) had no effect. CONCLUSION: Noggin, as an embryonic gene expressed in adult hippocampus, plays an important role in the process of learning and memory formation.

Animals↗