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Results for “Spatial Learning”

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At least 289 records · Page 16Linked to original sources

PubMed1999

The effects of subdural haematoma on spatial learning in the rat.

Although memory deficits are one of the most persistent consequences of human subdural haematoma, cognitive functioning has hardly been investigated in the rat subdural haematoma model. In the present study, the effects on spatial learning of right- and left-sided unilateral subdural haematoma and of bilateral subdural haematoma induced above the sensorimotor cortical areas were evaluated. Spatial learning was assessed by standard acquisition in the Morris water escape task (five sessions). Additional issues addressed were sensorimotor functioning (footprint analysis), recovery of cognitive functioning (tested by an overtraining and a reversal training) and replicability of induced cognitive deficits. Following unilateral subdural haematoma surgery, hardly any impairments in the Morris water escape task were observed: rats with a unilateral right-sided subdural haematoma showed very mild, transient deficits, whereas rats with left-sided subdural haematoma were indistinguishable from controls. Bilateral subdural haematoma surgery led to a clear, although transient, performance deficit. We conclude that animals with bilateral subdural haematoma may provide a promising cognitive deficit model for investigating recovery of function.

Animals↗

PubMed2001

Differential activation of hippocampus and amygdala following spatial learning under stress.

We examined the activation of memory-related processes in the hippocampus and the amygdala following spatial learning under stress, in the rat. Animals were trained in a water maze in a massed spatial task under two stress conditions (cold and warm water). In the dorsal CA1, training was accompanied by increased phosphorylation of ERK2 only in animals that have acquired the task (irrespective of whether they were trained in cold or warm water). In the amygdala, significant activation of ERK2 was found only in animals that learned the task well under high levels of stress. Hence, the results suggest that the amygdala and the hippocampus are differentially activated following spatial learning, depending on the level of stress involved.

Amygdala↗

PubMed2003

Intradimensional and extradimensional shifts in spatial learning.

Animals trained on 2 discriminations learn the 2nd rapidly if the relevant stimuli are from the same dimension as the 1st (an intradimensional or ID shift) but slowly if the relevant stimuli for the 2 problems are from different dimensions (an extradimensional or ED shift). Four experiments examined ID and ED shifts in spatial learning. Rats trained on 2 spatial problems learned the 2nd more rapidly than rats whose 1st problem had been nonspatial. But this difference between ID and ED shifts depended on the spatial relationship between rewarded (S+) and unrewarded (S-) alternatives in the 2 spatial problems. The results imply that rats trained on a spatial discrimination do not learn to attend to all spatial landmarks but only to those that serve to differentiate S+ and S-.

Animals↗

PubMed1995

(S)-WAY 100135, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine.

Scopolamine, 3.75 micrograms/microliters infused bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy but had no effect on choice latency or errors of omission in rats trained in a two-platform spatial discrimination task. Administered subcutaneously at 3 and 10 mg/kg 30 min before each training session, N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpropanami de dihydrochloride ((S)-WAY 100135), a 5-HT1A receptor antagonist, prevented the impairment of choice accuracy induced by intrahippocampal scopolamine. No subcutaneous dose of (S)-WAY 100135 by itself modified the acquisition of spatial learning. Administered into the dorsal hippocampus 15 min before each training session, (S)-WAY 100135 at doses of 0.2, 1 and 5 micrograms/microliters did not affect the acquisition of spatial learning but dose dependently prevented the impairment of choice accuracy caused by scopolamine, 3.75 micrograms/microliters infused into the same area. These findings suggest that blockade of 5-HT1A receptors can compensate the loss of cholinergic excitatory input on pyramidal cells, probably by favouring the action of other excitatory transmitters.

Animals↗

PubMed1997

Studies on the influence of enriched-environment housing combined with systemic administration of an alpha2-adrenergic antagonist on spatial learning and hyperactivity after global ischemia in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether an enriched housing environment and/or systemic administration of the alpha2-adrenergic receptor antagonist atipamezole facilitate the rate of spatial learning after global ischemia in rats. METHODS: Carotid arteries were closed for 20 minutes after permanent cauterization of vertebral arteries on the previous day. Enriched-environment housing and drug/saline treatment were begun 3 days after ischemia. For rehabilitation, housing in an enriched environment was combined with exploration in a labyrinth. Behavioral tests (the open-arena test and water-maze learning set task) were performed after 1-week periods of drug/saline treatment three times. In addition, the open-arena test was performed to evaluate the baseline level of animals 2 days after the induction of ischemia and at the end of the experiment, when the water-maze task was assessed in another room. RESULTS: Rats housed in an enriched environment after ischemia showed better acquisition of the water-maze learning set task after 1 week of housing. The influence of atipamezole treatment on this parameter did not reach statistical significance. In the open-arena test, ischemic animals were slightly hyperactive; however, this symptom was eliminated by housing in an enriched environment. CONCLUSIONS: The present data suggest that housing in an enriched environment facilitates the rate of spatial learning in rats with global ischemia. Rehabilitation also alleviated the hyperactivity observed in ischemic animals.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2000

Deficits in spatial learning and nicotinic-acetylcholine receptors in older, spontaneously hypertensive rats.

Spontaneously hypertensive rats are often used as models of attention deficit hyperactivity disorder and to investigate the effects of hypertension on cognitive function. Along with the wide variety of cardiovascular anomalies, these animals as young adults also exhibit deficits in memory and attention and central nicotinic-acetylcholine receptor sites. These findings may have particular significance since nicotinic receptors appear to be involved in the regulation of cerebral circulation and mnemonic function. Furthermore, a lack of high affinity nicotinic receptors (in knockout mice) has also been shown to accelerate both the structural and cognitive degeneration associated with age, findings that may be especially relevant to age-related memory disorders such as Alzheimer's Disease where large deficits in nicotinic receptors are observed. Since spontaneously hypertensive rats appear to be both memory-impaired and deficient in nicotinic receptors at a young age (compared to the non-hypertensive phenotype, Wistar-Kyoto rats), we were interested to learn if these conditions were exacerbated in older animals with particular interest in specific nicotinic receptor subtypes in memory areas of the brain. Spatial learning was assessed in 15-month-old subjects of each phenotype (i.e. hypertensive and non-hypertensive) using a two-phase water maze paradigm, and nicotinic receptors were measured via autoradiography with [125I]-alpha-bungarotoxin and [3H]-epibatidine. In the water maze, both groups learned to locate a hidden platform as indicated by progressively shorter latencies across training days, however, Wistar-Kyoto rats were more efficient in both phases. While the number of both bungarotoxin and epibatidine binding sites was lower in the hypertensive rats across several brain regions, in the case of epibatidine binding, the magnitude of the difference and the number of areas affected was generally greater and included areas important for spatial learning (e.g. frontal and entorhinal cortex). In a direct comparison between 3-month-old and 15-month-old rats of each phenotype, epibatidine sites were markedly reduced by age (i.e. by greater than 50% in some cases) across multiple brain regions in both groups, although Wistar-Kyoto rats appeared to be more substantially affected by age. These data further support the use of the spontaneously hypertensive rat as model for studying learning-impairment and reduced central nicotinic receptors and also indicate that these characteristics persist and (in the case of high affinity nicotinic receptor cites) worsen with age.

Acetylcholine↗

PubMed1995

NGF deprivation of adult rat brain results in cholinergic hypofunction and selective impairments in spatial learning.

Cholinergic hypofunction has often been correlated with a variety of behavioural impairments. In the present study, adult Wistar rats were intraventricularly infused with antibodies to nerve growth factor (anti-NGF) to examine the effects on cholinergic neurons of the basal forebrain, and on behavioural performance. Immunocytochemical techniques indicated that chronically infused anti-NGF penetrates into the basal forebrain, cortex, striatum, corpus callosum and hippocampus, confirming previous findings after a single injection. Treatment with anti-NGF for 1 or 2 weeks resulted in a significant decrease of 27-33% in density of choline acetyltransferase immunostaining of the cholinergic cell bodies in the medial septum and vertical diagonal band, and a 26% reduction in choline acetyltransferase enzyme activity in the septal area. An array of spatial learning Morris water maze tasks was used to distinguish between acquisition skills and the flexible use of learned information in novel tests. Rats subjected to the spatial learning paradigm received anti-NGF infusion for 2 weeks prior to and for another 2 weeks during the behavioural testing. The anti-NGF-treated animals were found to be no different from those receiving control serum in the Morris water maze acquisition task, either in the latency to find the platform or in the time spent searching in the training quadrant when the platform was removed. However, in consecutive extinction trials, anti-NGF rats continued to search in the empty training quadrant, suggesting the occurrence of perseveration; control rats expanded their search over other areas of the pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Hippocampal corticosteroid receptor mRNA expression and spatial learning in the aged Wistar rat.

The expression of mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA in the hippocampus of aged (18-24 months) and young (7 months) Wistar rats in relation to spatial learning in the water maze was investigated. All aged rats showed impaired performance of the task to locate a hidden platform compared to young controls, but the Wistar strain as a whole showed inferior performance to a group of young Lister hooded controls (added for the purposes of comparison) with even young Wistar rats apparently failing to learn platform location. The aged Wistar rats spent nearly 70% of their time near the side walls of the pool throughout the 5 days of training, while the young Wistar controls showed a gradual reduction in the percentage time spent there. MR and GR mRNA expression were unaltered in any hippocampal subregion in aged rats compared to young controls. Plasma corticosterone levels were also unchanged in aged rats. These results show that alterations in hippocampal corticosteroid receptor gene expression are not an inevitable consequence of aging in the rat, but that aging may be associated with strategy changes in the performance of a spatial learning task that are independent of glucocorticoid hypersecretion or alterations in hippocampal corticosteroid receptor mRNA expression.

Aging↗

PubMed1997

Nociceptin/orphanin FQ microinjected into hippocampus impairs spatial learning in rats.

The newly discovered peptide nociceptin/orphanin FQ has been found to increase reactivity to pain and to influence locomotor activity after intracerebroventricular administration. This study investigated the possible role of hippocampal nociceptin/orphanin FQ in spatial learning and in spontaneous locomotion. Male rats were trained in the Morris water task after microinjection of 10 nmol nociceptin/orphanin FQ or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Nociceptin/orphanin FQ was found to severely impair spatial learning without interfering with swimming performance. Intrahippocampal injection of nociceptin/ orphanin FQ markedly decreased exploratory locomotor activity including vertical movements (rearing). The data suggest that nociceptin/orphanin FQ is a potent modulator of synaptic plasticity within the hippocampus.

Animals↗

PubMed2001

Stimulation of 5-HT(1A) receptors in the dorsal raphe ameliorates the impairment of spatial learning caused by intrahippocampal 7-chloro-kynurenic acid in naive and pretrained rats.

OBJECTIVE: The present study investigated the effect of stimulating 5-HT(1A) receptors in the dorsal raphe on the impairment of spatial learning caused by intrahippocampal 7-chloro-kynurenic acid (7-Cl-Kyn) in naive rats and in rats familiar with the general requirements of the task. METHODS: A week after implantation of cannulae to give access to the dorsal raphe (DR) and the CA1 region of the dorsal hippocampus, rats started their 5 days acquisition training on a two-platform spatial discrimination task in a water maze. On each acquisition day, WAY 100635 and 8-OH-DPAT alone or in combination were injected into the dorsal raphe (DR) 5 min before intrahippocampal injections of 7-Cl-Kyn which was given 10 min before the training session. Similar experiments were conducted in rats that had been familiarized with the general requirements of the task by pretraining them in the water maze in the absence of distal cues. RESULTS: 7-Cl-Kyn (3 microg/microl), injected bilaterally in the CA1 region of the dorsal hippocampus, impaired choice accuracy with no significant effect on choice latency. Rats treated with 7-Cl-Kyn tended to spend more time swimming close to the pool walls and made more errors of omission than controls in the first two sessions. Administered into the DR, the 5-HT1A receptor agonist 8-OH-DPAT (1 microg/0.5 microl) had no effect on any parameter of rats' performance but antagonized the impairment of choice accuracy caused by intrahippocampal 7-Cl-Kyn. Injected into the DR, 1 microg/0.5 microl WAY 100635, a 5-HT(1A) receptor antagonist, had no effect on rats' performance or on the impairment caused by intrahippocampal 7-Cl-Kyn, but antagonized the effect of 8-OH-DPAT on the 7-Cl-Kyn-induced deficit. The non-mnemonic behavioral disturbances shown by naive rats treated with 7-Cl-Kyn were greatly reduced in pretrained rats which, nevertheless, showed a marked impairment of choice accuracy similar to that of naive rats. As in previous experiments, administration of 1 microg/0.5 microl 8-OH-DPAT in the dorsal raphe antagonized the impairment of choice accuracy caused by intrahippocampal 7-Cl-Kyn without any effect on other parameters of rats' performance. CONCLUSIONS: The results show that stimulation of presynaptic 5-HT(1A) receptors in the dorsal raphe counteracts the deficit in spatial learning caused by a reduced NMDA-mediated excitatory input on pyramidal cells in the hippocampus. The possible mechanisms and the importance of these findings for the symptomatic treatment of memory disorders in man are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2004

Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory.

Lesions restricted to the dorsal, but not the ventral, hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the ventral hippocampus are involved differentially in spatial reference and spatial working memory using a four-baited/four-unbaited version of the eight-arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within-subjects within-task comparison between the two forms of memory functions. Rats with N-methyl-d-aspartic acid-induced excitotoxic lesions of the dorsal hippocampus, ventral hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the ventral hippocampus, with the former being preferentially involved in spatial learning.

Animals↗

PubMed1990

A dose-related impairment of spatial learning by the NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5).

This paper describes an experiment which further tested the hypothesis that activation of N-methyl-D-aspartate receptors plays an important role in the neural mechanisms underlying certain kinds of learning and memory. The results demonstrate that a selective N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovalerate, causes a dose-related and correlated impairment of both spatial learning and hippocampal long term potentiation in vivo. No dose of D-2-amino-5-phosphonovalerate was found to block long term potentiation without affecting spatial learning. These data therefore support the proposed link between long term potentiation and certain kinds of learning, and the role of N-methyl-D-aspartate receptors in both processes.

2-Amino-5-phosphonovalerate↗

PubMed1998

Testing the NMDA, long-term potentiation, and cholinergic hypotheses of spatial learning.

The problems and issues associated with the use of pharmacological antagonists in studies on learning and memory are considered in a review of the role of N-methyl-D-aspartate (NMDA) receptors, NMDA receptor-mediated long-term potentiation (LTP), and muscarinic receptors in spatial learning in the water maze. The evidence indicates that neither NMDA nor muscarinic receptors, nor NMDA receptor-mediated LTP, are required for spatial learning, although they might normally contribute to it. Detailed behavioral analyses have indicated that the water maze task is more complex than generally has been appreciated, and has a number of dissociable components. Naive rats trained under NMDA or muscarinic antagonism display sensorimotor disturbances that interfere with their ability to acquire the task. Rats made familiar with the general requirements of the task can learn the location of a hidden platform readily under NMDA or muscarinic antagonism. The ability of a rat to acquire the water maze task depends on its ability to apply instinctive behaviors to performance of the task in an adaptive manner. The instinctive behaviors undergo modification as the rat learns the general strategies required in the task. The evidence suggests that at least some of the plastic changes involved in acquiring the task occur in existing neural circuits situated in widespread areas of the brain, including sensory and motor structures in the cortex and elsewhere, and are therefore difficult to distinguish from existing sensorimotor mechanisms. More generally, the findings indicate the difficulty of inferring the occurrence or nonoccurrence of learning from behavior, and the difficulty of causally linking the action of particular receptor populations with the formation of specific memories.

Animals↗

PubMed1996

The effect of continuous intraventricular infusion of L1 and NCAM antibodies on spatial learning in rats.

Recent studies suggest a role of the neural cell adhesion molecules L1 and NCAM in mechanisms of memory storage. In the present study we analyzed the effect of continuous intraventricular infusion of polyclonal antibodies directed against L1 (antiL1) or NCAM (antiNCAM) on the performance of male Wistar rats during the acquisition and retention of a spatial learning task (Morris water-maze). In this task animals have to learn the spatial position of a hidden escape platform in a water tank to escape onto it. During acquisition of the task animals with continuous infusion of antiNCAM - but not those infused with antiL1 - showed day-dependent attenuated learning in comparison to controls (P = 0.001). Control animals were either injected with vehicle (PBS) or with polyclonal antibodies raised against liver cell membrane. When the escape platform was removed during the retention test (transfer test), the performance of animals continuously infused with antiL1 as well as those continuously infused with antiNCAM showed an impaired search pattern when compared with the performance of control animals (P = 0.001 and 0.04, respectively). Whereas control animals spent up to 46% of their time searching for the platform in the correct quadrant, the time antiL1- and antiNCAM-infused animals spent in this quadrant was closer to chance level (30.5% and 36.5%), respectively). The present data provide additional support for an involvement of the two adhesion molecules L1 and NCAM in synaptic plasticity underlying memory storage.

Animals↗

PubMed2005

Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemia.

Enriched environment (EE) has been shown to increase neurogenesis in the adult brain. The aim of this study is to determine the effect of EE and spatial learning on neurogenesis following ischemic stroke. Male adult SD rats were subjected to sham surgery or distal middle cerebral artery occlusion (MCAO). MCAO induced a transient increase followed by a sustained depression of progenitor cell proliferation and neuroblast production below baseline level in both ipsilateral and contralateral DG compared to sham. Increased neuronal differentiation and neurogenesis in the DG were observed in both sham and MCAO rats following 8 weeks in the EE combined with spatial learning, compared to rats housed in the standard environment. EE/Learning also restored the total number of neuroblasts in the DG after MCAO compared to sham. Furthermore, EE/learning enhanced the density of NeuN positive cells in the ischemic penumbra, though no new neurons were detected in this region.

Animals↗

PubMed1999

Genetic differences in spatial learning between Dark Agouti and Sprague-Dawley strains: possible correlation with the CYP2D2 polymorphism in rats treated neonatally with methamphetamine.

Following neonatal exposure to d-methamphetamine, adult rats have previously been shown to exhibit augmented acoustic startle and spatial learning deficits. d-Methamphetamine is structurally similar to several phenylethylamines that are metabolized by CYP2D6. In humans, allelic differences in the CYP2D6 confer the extensive or poor metabolizer phenotype for the more than three dozen drugs that are members of the CYP2D6-mediated 'debrisoquine/sparteine panel.' An analogous genotype exists with the CYP2D2 gene in rats. Female Dark Agouti rats show the poor metabolizer phenotype, whereas Sprague-Dawley rats show the extensive metabolizer phenotype; male Dark Agouti rats are intermediate. We sought to test the possibility that these strains might exhibit altered d-methamphetamine-induced developmental neurotoxicity. Dark Agouti and Sprague-Dawley litters (11-20 days of age) were given d-methamphetamine or vehicle alone subcutaneously twice daily (15 mg/kg). Offspring were assessed as adults (beginning at 50 days of age) on acoustic startle, straight-channel swimming, and spatial learning and memory in a Morris hidden platform maze. Increases in d-methamphetamine-induced acoustic startle were found in both male and female Dark Agouti rats, but not Sprague-Dawley rats. In the Morris maze, d-methamphetamine-induced spatial navigation deficits were found in both strains among males, suggesting some mechanism other than the CYP2D2 polymorphism. In contrast, among females only the d-methamphetamine-treated Dark Agouti rats showed deficits in spatial navigation. The maze deficits in Dark Agouti females, and enhanced acoustic startle in Dark Agouti females and males, support the hypothesis that the CYP2D2 poor metabolizer phenotype confers increased vulnerability to d-methamphetamine-induced developmental neurotoxicity, indicating that the parent drug rather than a CYP2D2-mediated metabolite is responsible for this behavioural defect--which occurs in adults who had been exposed to d-methamphetamine during the neonatal period.

Animals↗

PubMed2005

Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

5,7-Dihydroxytryptamine↗

PubMed1993

Bilateral injections of beta A(25-35) + IBO into the hippocampus disrupts acquisition of spatial learning in the rat.

Focal deposits of beta-amyloid (beta A) in the hippocampus have been implicated in Alzheimer's disease. In this study we assessed the effects of bilateral injections into the hippocampus of beta A(25-35), a combination of beta A(25-35) with ibotenic acid (IBO), and IBO on spatial learning in the rat. Bilateral injections of beta A(25-35) into the hippocampus together with IBO (which by itself has no neurotoxic effects) produced a dramatic disruption in the acquisition of a spatial learning in the rat. Separate injections into the hippocampus of beta A(25-35) or the incubated form of beta A(25-35) alone failed to significantly affect maze acquisition in the rat. Histological examination revealed that only the combination of beta A(25-35) with IBO produced a lesion along with focal deposits in the hippocampus.

Amyloid beta-Peptides↗