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PubMed2005

Effects of the acoustic environment on learning in rats.

Although noise of moderate intensity is commonly present during experiments on animal learning and memory, its effects have usually not been considered. The present study investigated how differences in the acoustic environment affect learning and memory under otherwise identical conditions. Genetically defined rats learned a complex maze in noise of moderate intensity (70 dB) or in quiet. Noise had a profound effect on learning and behaviour. Noise-exposed rats made fewer errors, explored less and finished their trials sooner. Results show that the acoustic environment is an important variable in studies with animal models of learning and memory. This might explain why differences in learning and behavioural scores occur across laboratories even when the same rodent strains and apparently identical experimental protocols are used. As the effects probably rely on neurotransmitter systems common in vertebrates, similar effects can be expected in other species including humans.

Acoustic Stimulation↗
PubMed2000

Repeated acquisition and performance chamber for mice: a paradigm for assessment of spatial learning and memory.

Molecular genetic manipulation of the mouse offers the possibility of elucidating the function of individual gene products in neural systems underlying learning and memory. Many extant learning paradigms for mice rely on negative reinforcement, involve simple problems that are relatively rapidly acquired and thus preclude time-course assessment, and may impose the need to undertake additional experiments to determine the extent to which noncognitive behaviors influence the measures of learning. To overcome such limitations, a multiple schedule of repeated acquisition and performance was behaviorally engineered to assess learning vs rote performance within-behavioral test session and within-subject utilizing an apparatus modified from the rat (the repeated acquisition and performance chamber; RAPC). The multiple schedule required mice to learn a new sequence of door openings leading to saccharin availability in the learning component during each session, while the sequence of door openings for the performance component remained constant across sessions. The learning and performance components alternated over the course of each test session, with different auditory stimuli signaling which component was currently in effect. To validate this paradigm, learning vs performance was evaluated in two inbred strains of mice: C57BL/6J and 129/SvJ. The hippocampal dependence of this measure was examined in lesioned C57BL/6J mice. Both strains exhibited longer latencies and higher errors in the learning compared to the performance component and evidenced declines in both measures across the trials of each session, consistent with an acquisition phenomenon. These same measures showed little or no evidence of change in the performance component. Whereas three trials per session were utilized with C57BL/65 mice in each component, behavior of 129/SvJ mice could only be sustained for two trials per component per session, demonstrating differences in testing capabilities between these two strains under these experimental conditions and thus precluding the ability to make systematic strain comparisons of learning capabilities. Hippocampal lesions in C57BL/6J mice resulted in substantially longer latencies and increased errors in the learning but not the performance component, demonstrating the importance of this region to spatial learning as measured in the RAPC. In aggregate, this positive reinforcement-based operant paradigm to evaluate murine spatial learning detects strain differences and hippocampal dependence and permits explicit differentiation of the impact of noncognitive contributions to learning measures on a within-subject, within-session basis.

Animals↗
PubMed2005

Hippocampal NMDA receptor subunit expression and watermaze learning in estrogen deficient female mice.

The aromatase knockout (ArKO) mouse is estrogen deficient. Using reverse-transcription and real-time PCR, we showed that transcript levels of the N-methyl-d-aspartate (NMDA) receptor subunit NR2B are significantly higher in the hippocampus of female ArKO mice compared to wild-type (WT) littermates. Expression levels of NR1, NR2A, but not NR2C, also tended to be higher in ArKO mice. In the Morris watermaze test for spatial memory, both genotypes displayed equal significant improvement in the latency in locating the invisible platform over the 5-day training period. These findings show that selective loss of estrogen synthesis is associated with changes in NMDA receptor subunit expression in the hippocampus but little change in spatial learning ability.

Animals↗
PubMed2000

DNA fragmentation factor 45 deficient mice exhibit enhanced spatial learning and memory compared to wild-type control mice.

Programmed cell death or apoptosis is a highly regulated physiological process that is critical in development, particularly in the central nervous system. The DNA fragmentation factor 45 (DFF45 or ICAD) is a subunit of a heterodimeric DNase complex that is crucial for DNA fragmentation and normal apoptosis. To examine the neurobiological consequences of lacking DNA fragmentation and timely apoptosis during mouse development in vivo, we compared spatial learning behaviors in DFF45 mutant and wild-type control mice. We found that DFF45 mutant mice exhibit enhanced spatial learning and memory compared to wild-type mice. Moreover, both the granule cell density and total granule cell number in the hippocampal dentate gyrus region are higher in the DFF45 mutant brains than in the wild-type brains. We propose that the increase in granule cell number in the dentate region due to the DFF45 mutation changes the neuronal network underlying spatial learning and memory in DFF45 mutant mice.

Animals↗
PubMedDate not supplied

Behavioural studies of MHC-congenic mice.

Behavioural studies of MHC-congenic mice and rats have focused primarily on mate choice and the ability to discriminate between strains by their urine odours, but these strains may differ in other behaviours, such as activity and ultrasonic vocalizations. Ivanyi (1978, Proc. Roy. Soc. Lord. 202, 117-158) has reviewed the physiological differences associated with the MHC, many of which could influence behaviour. We have started a systematic study of behavioural development and adult behaviour in MHC-congenic mice. A developmental test battery (growth, rate, locomotion, grooming, eye opening, ultrasonic vocalizations, etc.) was used to examine differences between C57BL/6J vs. B6-H-2bml and C57BL/10SnJ vs. B10.BR/sgSnJ mice. A test battery of spontaneous behaviours (activity, exploration, ultrasonic vocalizations, etc.) was used to examine behavioural differences between adult C57BL/6J vs. B6-H-2bml; and C57BL/10SnJ vs. B10.BR/sgSnJ mice. Differences in development and in adult behaviours between these MHC-congenic strains is discussed in relation to possible neural, endocrine and immune system differences. Future studies will compare MHC-congenic mice on levels of anxiety, sociosexual behaviour and on learning paradigms.

Animals↗
PubMed2004

Effect of antibodies to nerve growth factor and serum albumin on the development and behavior of mice.

We studied physical development, behavioral characteristics, and learning capacity in the offspring of mice immunized with nerve growth factor and bovine serum albumin. High titer of antibodies to these factors in the blood of pregnant females determines high levels of these antibodies in the blood of their pups. These changes modulate physical development, behavior, and learning capacity of rat pups. The effects of these antibodies differed in the strength and directionality. Antibodies to nerve growth factor more markedly retarded physical development, reduced learning capacity, and considerably increased pain thresholds in animals.

Animals↗
PubMed2006

Context-dependent modulation by D(1) receptors: differential effects in hippocampus and striatum.

Place-specific firing by hippocampal and striatal neurons was recorded simultaneously following injection of a D(1) receptor antagonist (SCH23390) and during spatial working memory task performance. SCH23390-induced changes in unit responses were observed during light and dark test conditions. Although hippocampal place field locations were altered by the contextual change, the reliability and specificity of place fields was disrupted only by combining D(1) antagonism and a change in context. Striatal place field locations were reorganized after either contextual change or D(1) antagonism, without altering place field reliability and specificity. Disrupted velocity encoding by place cells in both regions was induced by darkness, whereas greater stability in acceleration encoding followed removal of D(1) receptor activity. Dopamine may differentially regulate hippocampal context learning and striatum-based predictive codes.

Action Potentials↗
PubMed2006

Molecular basis of memory loss in the Tg2576 mouse model of Alzheimer's disease.

Understanding the pathophysiology and treatment of Alzheimer's disease is vitally important. Alzheimer's disease threatens to affect currently at least 30% of all individuals currently alive in the 12 most financially developed countries, unless interventions are discovered to prevent or treat the disease. Although memory loss is the cardinal symptom of Alzheimer's disease, the pathophysiological mechanisms leading to cognitive deficits are poorly understood. It is difficult to address this problem in human studies, and impossible in cultured cells. Therefore, animal models are needed to elucidate the molecular mechanisms leading to dementia. A large number of animal models have focussed upon the role of amyloid plaques in the pathogenesis of Alzheimer's disease, because amyloid plaques are an essential diagnostic feature of the disease. However, the mechanism by which amyloid plaques or their principal molecular constituent, the amyloid-beta protein (Abeta), disrupt cognitive function is not well understood. Herein, I describe my perspective on what we have learned about how Abeta impairs memory from research on Alzheimer's disease in mice and rats.

Alzheimer Disease↗
PubMed2006

Long-term tryptophan administration enhances cognitive performance and increases 5HT metabolism in the hippocampus of female rats.

It has been shown in various studies that increase in serotonergic neurotransmission is associated with increased memory consolidation whereas low brain 5HT impairs memory performance. In the first phase of our study we found that tryptophan (TRP) administration for 6 weeks increased plasma TRP and whole brain TRP, 5HT and 5HIAA levels. Many brain regions are involved in the learning process but particularly the hippocampus is known to have key role in learning and memory. The present study was therefore designed to investigate the effects of TRP loading particularly on hippocampal 5HT metabolism and cognitive performance in rats. TRP-treated rats demonstrated spatial enhancement as evidenced by a significant decrease in time to find the hidden food reward in radial arm maze test (RAM). The important finding of the present study was the greater increase in the 5HT metabolism in hippocampus than in any other brain region of the TRP-treated rats. This increased 5HT metabolism in the hippocampus emphasizes the involvement of this region in memory process.

Animals↗
PubMed2007

Aged SOD overexpressing mice exhibit enhanced spatial memory while lacking hippocampal neurogenesis.

The recent finding that hippocampal slices from aged mice overexpressing the gene for superoxide dismutase (SOD) exhibit long-term potentiation (LTP) of reactivity to afferent stimulation that is significantly larger than that produced in aged wild-type (wt) mice has encouraged the exploration of the effects of reactive oxygen species (ROS) on learning in aged mice. In addition, young-adult and aged wt and SOD transgenic mice were used in an attempt to correlate adult neurogenesis with spatial learning. Aged wt and SOD mice exhibited a 90% reduction in doublecortin-labeled new dentate gyrus neurons as compared to young mice, with no significant difference between genotypes. In addition, aged SOD mice exhibited better performance than wt controls in both reference and working memory tasks in a water maze. These findings provide a behavioral measure to demonstrate that excessive production of H2O2 is beneficial in aged mice.

Aging↗
PubMed2001

Dorsal striatal head direction and hippocampal place representations during spatial navigation.

Several theories of basal ganglia function describe a striatal contribution to learning that is independent of hippocampal function. This study examined the question of whether the striatum should be regarded as functioning independently of or acting in concert with limbic structures. Dorsal striatal head direction cells and hippocampal place cells were recorded in parallel while rats performed a hippocampal-dependent radial maze task. Changes in the directional preference of head direction cells and the location of place fields were compared following alterations of the sensory environment. When familiar visual cues were presented in new spatial arrangements, or when new visual cues were placed in a familiar environment, rotations of directional preferences were consistent with the mean place-field response. When familiar visual and nonvisual cues were presented in conflict, or when rats were exposed to novel environments, the responses of the two cell types were inconsistent relative to each other. This pattern suggests that current perceptions and expectations of familiar spatial contexts may dynamically modulate the relationship between hippocampus and dorsal striatum.

Animals↗
PubMed1975

[L'"apprentissage social" chez le termite de santonge].

Termites, when they are in groups, are able to learn a maze between their nest and the food. Workers lay an odorous trail on the most direct way. The gallery will be built on this train. Kinesthetic information also seem implicated.

Animals↗
PubMed2005

Spatial-specificity of single-units in the hippocampal formation of freely moving homing pigeons.

The importance of space-specific single-unit activity for hippocampal formation (HF)-mediated learning and memory in rodents has been extensively studied, yet little is known about how the unit findings in rodents generalize to other vertebrate species. We report a first assessment of the space-specific single-unit activity recorded from the HF of homing pigeons as they moved through a plus maze for food reward. Rate maps of pigeon HF single-unit activity typically revealed multiple regions (2-5 per cell) of increased activity (on average, 2.5 times higher than other regions of the maze) that in 27% of slow-firing cells was reliably space-specific over time. The qualitative appearance of rate maps and the degree of spatial-specificity observed for most all pigeon HF cells suggests more modest space-specific activity than typically reported for rat hippocampal cells. The nature of space-specific activity in the pigeon HF includes (1) often transiently reliable regions of increased activity for many cells, (2) multiple patches of activity that were sometimes observed in analogous maze areas, and (3) cells displaying substantial decreases in firing rate between baseline and maze-run conditions that could not be explained by a simple relationship between firing rate and a pigeon's speed. These observations suggest that pigeon HF cells may be coding for an unspecified behavioral/motivational/environmental factors in addition to a pigeon's momentary location. The data further suggest that the spatial ecology and evolutionary history of different species may be a critical feature shaping how HF neurons capture properties of space.

Action Potentials↗
PubMed2005

Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat.

An enriched environment consists of a combination of enhanced social relations, physical exercise and interactions with non-social stimuli that leads to behavioral and neuronal modifications. In the present study, we analyzed the behavioral effects of environmental complexity on different facets of spatial function, and we assessed dendritic arborisation and spine density in a cortical area mainly involved in the spatial learning, as the parietal cortex. Wistar rat pups (21 days old) were housed in enriched conditions (10 animals in a large cage with toys and a running wheel), or standard condition (two animals in a standard cage, without objects). At the age of 3 months, both groups were tested in the radial maze task and Morris water maze (MWM). Morphological analyses on layer-III pyramidal neurons of parietal cortex were performed in selected animals belonging to both experimental groups. In the radial maze task, enriched animals exhibited high performance levels, by exploiting procedural competencies and working memory abilities. Furthermore, when the requirements of the context changed, they promptly reorganized their strategies by shifting from prevalently using spatial procedures to applying mnesic competencies. In the Morris water maze, enriched animals more quickly acquired tuned navigational strategies. Environmental enrichment provoked increased dendritic arborisation as well as increased density of dendritic spines in layer-III parietal pyramidal neurons.

Animals↗
PubMed1999

American ginseng extract reduces scopolamine-induced amnesia in a spatial learning task.

OBJECTIVE: To determine if HT-1001, an extract of American ginseng, affects scopolamine-induced memory and performance deficits in a spatial learning task, alters brain concentrations of aminergic neurotransmitters, and alters choline uptake in synaptosome preparations. DESIGN: Animal study. ANIMALS: 48 Sprague Dawley rats. INTERVENTIONS: Long-term oral administration of a test material or control solution. Intraperitoneal administration of scopolamine (2 mg/kg) 30 minutes before testing. OUTCOME MEASURES: Performance on Morris water maze task, choline uptake, aminergic neurotransmitter analysis, in vitro monoamine oxidase analysis (of compounds). RESULTS: HT-1001 protected against scopolamine-induced amnesia and increased choline uptake in synaptosomal preparations. HT-1001 did not alter brain concentrations of norepinephrine, dopamine, 5-HT (serotonin), 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleactic acid. HT-1001 had a very weak ability to inhibit monoamine oxidase activity in vitro. CONCLUSIONS: HT-1001 demonstrates a capacity to protect against scopolamine-induced memory deficits.

Animals↗
PubMed1997

Intrahippocampal injections of phencyclidine but not naloxone disrupt acquisition of a spatial continuous recognition memory task.

Rats with 36 nM or 54 nM of phencyclidine (PCP), 36 nM of naloxone or saline injected into the dentate gyrus of the hippocampus were tested for acquisition of a spatial continuous recognition memory task. Results indicate that relative to controls and rats with 36 nM of PCP or 36 nM of naloxone injections, rats with 54 nM of PCP injections were impaired in acquisition of the task across all lags as measured by increased in latency for repeated items. Since it is assumed that successful learning of this continuous recognition memory task depends upon processes associated with consolidation of new learning into long term memory, it appears that high doses of PCP, but not naloxone are sufficient to impair this process.

Animals↗
PubMed2006

[Effect of long-term intake of Y3+ in drinking water on learning-memeory functions and growth-development of rats].

OBJECTIVE: The aim of this paper was to learn the effect of long-term intake of Y3+ in drinking water on learning-memory function and growth-development of rats. METHODS: The rats were fed with water dissolved different level Y3+ (0, 0.534, 53.4, 5340 mg/L) for 6 months, pregnant rate, survive rate, bear rate, variety in weight were calculated, the learning-memory function was observed by step-down test. RESULTS: The results showed that a significantly decrease in electric shock period and an increase in incubation period were observed for the low dose group, in contrast, a significantly increase in electric shock period and error times, and an decreases in weight and survive rate were observed for the high dose group. CONCLUSION: Y3+ in 0.534 mg/L might improve the function of learning and memory in rats, and that Y3+ in 5340mg/L could restrain both the function of learning-memory functions and growth-development in rats.

Animals↗
PubMed2004

Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: possible mechanisms for corticosterone on opiate addiction.

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation (approximately 20%) to synaptic depression (approximately 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

Animals↗