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Results for “Spatial Learning”

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PubMed2002

Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments.

Deregulation of glycogen synthase kinase-3 (GSK-3) activity in neurones has been postulated as a key feature in Alzheimer's disease (AD) pathogenesis. This was further supported by our recent characterization of transgenic mice that conditionally over-express GSK-3beta in hippocampal and cortical neurones. These mice, designated Tet/GSK-3beta, showed many of the biochemical and cellular aspects of AD neuropathology such as tau hyperphosphorylation and somatodendritic localization, decreased nuclear beta-catenin, neuronal death and reactive gliosis. Tet/GSK-3beta mice, however, did not show tau filament formation up to the latest tested age of 3 months at least. Here we report spatial learning deficits of Tet/GSK-3beta mice in the Morris water maze. In parallel, we also measured the increase in GSK-3 activity while further exploring the possibility of tau filament formation in aged mice. We found a significant increase in GSK-3 activity in the hippocampus of Tet/GSK-3beta mice whereas no tau fibrils could be found even in very old mice. These data reinforce the hypothesis of GSK-3 deregulation in AD pathogenesis, and suggest that Tet/GSK-3beta mice can be used as an AD model and, most remarkably, can be used to test the therapeutic potential of the selective GSK-3 inhibitors that are currently under development. Additionally, these experiments suggest that destabilization of microtubules and alteration of intracellular metabolic pathways contribute to AD pathogenesis independent of toxicity triggered by the aberrant tau deposits.

Animals↗

PubMed2003

Motor coordination, exploration, and spatial learning in a natural mouse mutation (nervous) with Purkinje cell degeneration.

The nervous mouse mutation causes a relatively selective degeneration of Purkinje cells in the cerebellar cortex. The mutants were compared to age-matched controls of the same background strain in tests of motor activity and coordination, spontaneous alternation, and spatial learning in the Morris water maze. As expected from their ataxia, the nervous mutants were impaired in stationary beam, coat-hanger, and rotorod tests of motor coordination. The nervous mutants were also impaired in the submerged but not in the visible platform condition of the Morris water maze, attributable to a spatial deficit, and displayed a higher level of motor activity in an automated chamber. The deficit in spontaneous alternation rates seen in nervous mutants is accountable by reduced motivation, disinhibition, or spatial disorientation.

Analysis of Variance↗

PubMed1988

Spatial learning potentiates the stimulation of phosphoinositide hydrolysis by excitatory amino acids in rat hippocampal slices.

Stimulation of phosphoinositide (PI) hydrolysis by excitatory amino acids (glutamate and ibotenate) or norepinephrine was potentiated in hippocampal slices from rats trained in an eight-arm radial maze, used as a test of spatial learning. No difference in basal or carbamylcholine-stimulated PI hydrolysis was found between control and trained animals. An increased PI response to excitatory amino acids and norepinephrine was not found in hippocampal slices prepared from animals trained in a shock conditioning avoidance test. These results suggest a possible involvement of specific glutamate receptors coupled with PI hydrolysis in the synaptic mechanisms underlying formation and/or storage of spatial memory.

Animals↗

PubMed2002

Effects of fimbria-fornix lesion and amyloid pathology on spatial learning and memory in transgenic APP+PS1 mice.

Transgenic mice carrying mutated human amyloid precursor protein (APPswe) and presenilin (PS1, A246E) genes develop first amyloid plaques around 9 months of age, but up to 18 months of age, amyloid depositions in these mice were largely restricted to the hippocampus, subiculum, and neocortex. To assess the behavioral consequences of amyloid accumulation in the hippocampal formation, we compared the effects of APP+PS1 (AP) genotype and fimbria-fornix (FFX) transection, either alone or combined, on various spatial learning and memory tasks. Both FFX-lesioned and AP mice were impaired in spatial navigation in the water maze, a typical hippocampal dependent task. Conversely, neither group of mice was impaired in a win-stay version of the radial arm maze (RAM) or position discrimination in the T-maze, tasks that do not depend on the hippocampus. FFX-lesioned mice were impaired in the win-shift version of the RAM, and in spontaneous and rewarded alternation in the T-maze, while AP mice performed equal to non-transgenic controls in all these working memory tasks, except long-term retention of the RAM task. AP mice thus appear to have a selective deficit in hippocampal dependent long-term memory, as do Alzheimer patients at early stage of the disease.

Amygdala↗

PubMed1993

Spatial learning in an enclosed eight-arm radial maze in rats with sodium arsanilate-induced labyrinthectomies.

Bilateral vestibular dysfunction was induced in Long-Evans male rats (n = 7) by intratympanic injections of sodium arsanilate (30 mg/side). Control rats (n = 6) received isotonic saline. Animals were tested for labyrinthine integrity by measuring air-righting and contact-righting reflexes. Rats were reduced to 85% of free-feeding body weight and tested in an enclosed 8-arm radial maze (1 trial/day over 10 days). Labyrinthectomized animals made significantly more errors (p < .001) and, unlike the controls, showed no significant improvement on this measure over acquisition training. These rats also made significantly more (p = 0.018) sequential same arm reentries and fewer sequential adjacent arm entries (p < .01). These findings demonstrate that information obtained from the vestibular system is very important in spatial learning in the rat.

Animals↗

PubMed1992

Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats.

Brain nerve growth factor (NGF) was determined in two groups of aged rats: 'good' and 'poor' performers. The animals were selected out of a population of 40 aged rats (26-28 months old) trained in a spatial learning task. Animals performing well in the test had significantly higher NGF in the hippocampus when compared to 'poor' performers. No differences in the levels of NGF were found in the cortex, septum and cerebellum. The results implicate hippocampal NGF in cognitive functioning of aged rats, and suggests that the forebrain cholinergic neuronal atrophy which has been observed in cognitively impaired aged rats may be due to reduced availability of target-derived NGF.

Aging↗

PubMed1998

50 Hz magnetic field effects on the performance of a spatial learning task by mice.

Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 microT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 microT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5 microT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible.

Analysis of Variance↗

PubMedDate not supplied

The effects of pentobarbital on spatial learning, motor coordination, and exploration.

Mice injected with either 8, 16 or 32 mg/kg of pentobarbital were as efficient as control subjects in learning and recalling the location of a submerged platform in a water maze. The highest dose of pentobarbital decreased fall latencies in the coat-hanger test of motor coordination. Exploratory activity was not affected by these doses of pentobarbital. The absence of a deficit in spatial learning and in exploratory activity occurred even at a dose sufficient to cause a deficit in motor coordination. These results stand in contrast to previous findings indicating spatial deficits in rats injected with benzodiazepines.

Analysis of Variance↗

PubMed1998

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning.

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and distinct distribution in the hippocampus, a brain region which is directly involved in the regulation of spatial orientation and learning. In this study, repeated subcutaneous administration of the mineralocorticoid receptor antagonist RU28318 (1.0 mg/100 g body weight), the glucocorticoid receptor blocker RU38486 (2.5 mg/100 g body weight), or a combination of both antagonists were investigated for their effects on working--and reference memory in morning and afternoon trials during 8 subsequent days in food rewarded spatial learning in a hole board task. Each rat received one dose of either vehicle (2% ethanol in PEG 400), RU28318, RU38486 or the combination of both antagonists directly after the first trial on training days 1, 3, 5, and 7. The experiments demonstrated that repeated blockade of mineralocorticoid receptors impairs reference memory reflected in the morning--as well as in the afternoon trial, whereas blockade of glucocorticoid receptors has little effect on this type of cognitive behaviour. Furthermore, combined blockade of MRs and GRs resulted in a decrease, in both daily trials, in reference memory as well as working memory performance. These findings suggest that in this spatial learning paradigm, the impairment of working memory required blockade of both receptor types, while reference memory performance involves predominantly the mineralocorticoid receptors.

Animals↗

PubMed1995

Spatial learning in male and female Long-Evans rats.

Male and female Long-Evans rats were tested in the Morris water maze at 6 months of age. A place training procedure, in which rats learned the position of a camouflaged platform, was followed by cue training, in which rats escaped to a visible platform. No sex difference was found in place learning ability. Search accuracy on probe trials, when the platform was unavailable, was also equivalent for the male and female groups. These results contrast with previous studies of rodents at younger ages, which have reported a male advantage in spatial learning. It is suggested that the age at which rats are assessed may be an important factor, possibly reflecting a different course in the relatively protracted maturation of the hippocampus in male and female rats. The results of this investigation are also discussed with reference to studies of sex differences for spatial abilities in humans.

Age Factors↗

PubMed2001

Beneficial effect of the sigma(1) receptor agonist PRE-084 against the spatial learning deficits in aged rats.

Sigma(1) (sigma(1)) receptor agonists showed anti-amnesic properties in pharmacological amnesia models. We now investigated whether the selective sigma(1) receptor agonist, 2-(4-morpholinoethyl)-1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084), could ameliorate spatial learning in aged animals, using a water-maze procedure. Wistar rats, 3 or 24 months old, were trained to locate a visible platform and then an invisible platform. Finally, a transfer test was performed during saline or PRE-084 treatment. Aged, but not adult, animals showed learning deficits unrelated to visual impairments. The PRE-084 treatment allowed aged animals to learn the new platform location, in terms of decreased latencies to the platform during training and increased presence in the quadrant during retention. The results of these experiments suggest a potential of selective sigma(1) receptor agonists as cognitive enhancers during ageing.

Aging↗

PubMed2003

Effects of the synthetic cannabinoid nabilone on spatial learning and hippocampal neurotransmission.

Cannabinoids, the active components of marijuana, affect memory and hippocampal neurotransmission. It has been claimed that nabilone, a synthetic cannabinoid endowed with antiemetic properties, has a peculiar profile of actions. We studied the effects of the drug on spatial learning and in vitro hippocampal CA1 electrophysiology in the rat. Nabilone (0.1, 0.5, and 1.0 mg/kg ip) does not impair place learning in a water maze task, whereas Delta(8)-tetrahydrocannabinol (Delta(8)-THC) disrupts this function. At concentrations ranging from 1 nM to 10 microM nabilone does not influence basal glutamatergic neurotransmission, which is decreased by Delta(8)-THC. Although cannabinoids have been consistently reported to affect synaptic plasticity, nabilone 1 microM does not change paired-pulse facilitation, long-term potentiation and the magnitude of long-term depression. However, the time course of the latter phenomenon is significantly changed by the drug, the depression being lower than in control experiments from 7 to 35 min postinduction. Altogether, our data indicate that there might be differences in the effects of agonists for central cannabinoid receptors, which could help to understand the pharmacology of this class of molecules. The results also suggest that amnesia induced by cannabinoids be possibly related to their effects on hippocampal neurotransmission. The study supports the use of nabilone in conditions the course of which is complicated by cognitive impairment.

Animals↗

PubMed2002

Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor.

In this study, the authors investigate changes in the presynaptic terminal of the dentate gyrus that accompany 2 types of hippocampal-dependent plasticity: spatial learning and long-term potentiation (LTP). Parallel changes occurred in the dentate gyrus of rats that had undergone training in the Morris water maze and had sustained LTP. In both cases, KCl-induced brain-derived neurotrophic factor release was increased, and this was accompanied by increased phosphorylation of TrkB and the mitogen-activated protein kinase, ERK. Glutamate release was also enhanced, and the data suggest that this may be a consequence of increased activation of TrkB and ERK. Because the data indicate that similar cellular modifications are shared by these 2 forms of plasticity, they provide circumstantial evidence that LTP satisfies some of the requirements of a memory-inducing cellular substrate.

Animals↗

PubMed1996

Spontaneous alternation, motor activity, and spatial learning in hot-foot mutant mice.

Hot-foot mutant mice, characterized by defective innervation of Purkinje cells and an ataxic gait, were less active than normal mice in a T-maze. In spontaneous alternation testing with either single or multiple trials, hot-foot mutants, contrary to normal mice, did not alternate above chance. Moreover, the mutants had a higher number of errors and higher escape latencies in a water-filled Z-maze. These results indicate that in addition to motor coordination deficits, these cerebellar mutants have deficits in spatial learning and perseverate choices of maze arms.

Animals↗

PubMed1987

Spatial learning and memory following fimbria-fornix transection and grafting of fetal septal neurons to the hippocampus.

The ability of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in developing cholinergic neurons, to ameliorate cognitive impairments induced by bilateral fimbria-fornix transections in rats was examined in three experiments using the Morris water-maze to test different aspects of spatial memory. Experiment 1. Rats with fimbriafornix lesions received either septal cell suspension grafts or solid septal grafts; normal rats and rats with lesions alone were used as controls. Sixteen weeks after surgery, the rats' spatial learning and memory were tested in the water-maze using a place test, designed to investigate place navigation performance, in which rats learned to escape from the water by swimming to a platform hidden beneath the water's surface. After 5 days of training, the rats were given a spatial probe test in which the platform was removed from the tank to test spatial reference memory. Experiment 2. The same rats used in Exp. 1 were tested in a delayed-match-to-sample, working memory version of the water-maze task. The platform was located in one of two possible locations during each trial, which was composed of 2 swims. If the rat remembered the location of the platform on the 2nd swim of a trial, it should find the platform more quickly on that swim, and thereby demonstrate working memory. Experiment 3. Prior to receiving fimbria-fornix lesions, normal rats were trained in a modification of the water-maze task using alternating cue navigation and place navigation trials (i.e., with visible or non-visible escape platforms). The retention and reacquisition of the place task and the spatial probe test were examined in repeated tests up to 6 months after the lesion and intrahippocampal grafting of septal cell suspensions. The effects of central muscarinic cholinergic receptor blockade with atropine were also tested. Normal rats performed well in both the place and spatial probe tests. In contrast, rats with fimbria-fornix lesions only were unable to acquire or retain spatial information in any test. Instead, these rats adopted a random, non-spatial search strategy, whereby their latencies to find the platform decreased in the place navigation tasks. Sixty to 80% of the rats with septal suspension or solid grafts had recovered place navigation, i.e., the ability to locate the platform site in the tank, in Exp. 1 and 3, and they showed a significantly improved performance in the working memory test in Exp. 2. Atropine abolished the recovered place navigation in the grafted rats, whereas normal rats were impaired to a lesser extent.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

PubMed2003

Spatial learning is delayed and brain-derived neurotrophic factor mRNA expression inhibited by administration of MK-801 in rats.

Brain-derived neurotrophic factor (BDNF) is involved in activity-dependent plasticity and interacts with the neurotransmitter glutamate. Glutamate N-methl-D-aspartate (NMDA) receptor activation increases BDNF expression, while BDNF facilitates NMDA activity, with both involved in spatial learning. Administration of the NMDA receptor antagonist MK-801 can impair this leaning. The interaction between NMDA and BDNF in learning is examined in this study. Adult male Sprague-Dawley rats received either i.p. MK-801 or saline and were trained to locate a submerged water maze platform. Sedentary and activity yoked groups were included for biochemical comparisons. Control rats quickly learned the platform location while MK-801-treated rats learned at a significantly slower rate (P < 0.0001). In situ hybridization for hippocampal BDNF mRNA indicated significant increases in the yoked and learning groups. However, MK-801 attenuated the BDNF mRNA increase in the learning and activity-yoked conditions (P < 0.05). Administration of MK-801 to the sedentary group did not alter baseline mRNA levels. These data suggest that BDNF expression is important for NMDA-dependent learning and memory. Interestingly, learning still occurs across trials independent of the NMDA and BDNF interaction. Increases in BDNF and NMDA activity may be significant components in learning and memory, and modulation of these systems may be beneficial for developing strategies to improve cognitive function.

Animals↗

PubMed2001

Selegiline combined with enriched-environment housing attenuates spatial learning deficits following focal cerebral ischemia in rats.

Selegiline (l-deprenyl) is an irreversible monoamine oxidase B (MAO-B) inhibitor that is suggested to have neuroprotective and neuronal rescuing properties. The present study investigated whether systemic administration of selegiline facilitates behavioral recovery after transient focal cerebral ischemia in rats using a combination of different behavioral tests (limb placing, foot slip, water maze, and Montoya's staircase test) to measure the outcome of recovery. Selegiline (0.5 mg/kg, SC) or 0.9% NaCl was administered once a day, beginning on the second day after induction of ischemia and continuing for 30 days. Selegiline administration combined with enriched-environment housing attenuated ischemia-induced spatial learning deficits in a water-maze task and enhanced performance of both the contralateral affected and ipsilateral nonaffected forelimbs in a staircase test. Selegiline administration alone was not beneficial in any of the tests. Subsequent histologic examination revealed that the infarct volumes were not different between the experimental ischemic groups. Thus, these results suggest that selegiline combined with enriched-environment housing reduces behavioral and cognitive deficits without affecting infarct size.

Animals↗

PubMed1991

Open field behaviours and spatial learning performance in C57BL/6 mice: early stage effects of chronic GM1 ganglioside administration.

One month intact C57BL/6 mice were treated with GM1 ganglioside for 3 consecutive weeks. At 2 months of age, treated and control mice were observed in the open-field situation and tested for spatial learning in a radial eight-arm maze. The results showed that, in the open-field, treated mice displayed less freezing but more rearing behavior than control animals. In the radial maze, GM1-treated mice made more correct path choices before the first error within each trial than control mice. However, this improvement was limited to the first stage of training. These results suggest an early stimulating effect of the GM1 ganglioside treatment which could facilitate adaptive reactions to new situations.

Animals↗