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Results for “Spatial Learning”

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PubMed2003

Effects of acute and repeated daily exposure to hypergravity on spatial learning in mice.

Studies in humans have revealed that exposure to altered gravity may lead to impairments in cognitive functions. The objective of this study was to test whether mice exposed to hypergravity using a centrifuge apparatus showed learning impairments in a spatial learning task. Mice rotating at 1G or at 2G acceleration gravity and non-rotating controls were tested for reactivity to a spatial change after either a single 1 h or five repeated 1 h daily rotations in the centrifuge. While no differences among groups were found in the performance after single exposure to altered gravity, 5 days of repeated exposures to 1G or 2G gravity conditions significantly affected mouse ability to discriminate a new spatial arrangement. Additionally, this effect was stronger in the animals repeatedly exposed to 2G rather than to 1G conditions.

Animals↗

PubMed2001

Spatial learning induces neurotrophin receptor and synapsin I in the hippocampus.

We report that rats learning a spatial memory task in the Morris water maze show elevated expression of the signal transduction receptor for BDNF and the synaptic associated protein synapsin I in the hippocampus. Nuclease protection assays showed maximal levels of TrkB and synapsin I mRNAs in the hippocampus by the time that asymptotic learning performance had been reached (Day 6). Increases in synapsin I mRNA were matched by changes in synapsin I protein as revealed by western blot analysis. Synapsin I is a downstream effector for the BDNF tyrosine kinase cascade pathway which has important roles in synaptic remodeling and function. Therefore, parallel changes in TrkB and synapsin I mRNAs suggest a role of the BDNF system in synaptic function or adaptation. Levels of TrkB mRNA in the hippocampus were attenuated after learning acquisition (Day 20), but synapsin I mRNA was still elevated, suggesting that the BDNF system may participate in events secondary to learning, such as strengthening of neural circuits. TrkB and synapsin I mRNAs showed an increasing trend in the cerebellum of learning rats and no changes were observed in the caudal cerebral cortex. The selectivity of the changes in trkB and synapsin I, affecting the hippocampus, is in agreement with the role of this structure in processing of spatial information. Behavioral regulation of neurotrophins may provide a molecular basis for the enhanced cognitive function associated with active lifestyles, and guide development of strategies to promote neural healing after CNS injury or disease.

Animals↗

PubMed2006

Changes in transcription within the CA1 field of the hippocampus are associated with age-related spatial learning impairments.

Aged rats display a broad range of behavioral performance in spatial learning. The aim of this study was to identify candidate genes that are associated with learning and memory impairments. We first categorized aged-superior learners and age learning-impaired rats based on their performance in the Morris water maze (MWM) and then isolated messenger RNA from the CA1 hippocampal region of each animal to interrogate Affymetrix microarrays. Microarray analysis identified a set of 50 genes that was transcribed differently in aged-superior learners that had successfully learned the spatial strategy in the MWM compared to aged learning-impaired animals that were unable to learn and a variety of groups designed to control for all non-learning aspects of exposure to the water maze paradigm. A detailed analysis of the navigation patterns of the different groups of animals during acquisition and probe trials of the MWM task was performed. Young animals used predominantly an allocentric (spatial) search strategy and aged-superior learners appeared to use a combination of allocentric and egocentric (response) strategies, whereas aged-learning impaired animals displayed thigmotactic behavior. The significant 50 genes that we identified were tentatively classified into four groups based on their putative role in learning: transcription, synaptic morphology, ion conductivity and protein modification. Thus, this study has potentially identified a set of genes that are responsible for the learning impairments in aged rats. The role of these genes in the learning impairments associated with aging will ultimately have to be validated by manipulating gene expression in aged rats. Finally, these 50 genes were functioning in the context of an aging CA1 region where over 200 genes was found to be differentially expressed compared to a young CA1.

Aging↗

PubMed2005

Abnormal expression of epilepsy-related gene ERG1/NSF in the spontaneous recurrent seizure rats with spatial learning memory deficits induced by kainic acid.

Previous epilepsy-related gene screen identified a spontaneous recurrent seizure (SRS)-related gene named epilepsy-related gene (ERG1) that encodes N-ethylmaleimide-sensitive fusion protein (NSF). To explore whether spatial learning memory deficits are relevant to SRS and whether hippocampal NSF expression is altered by SRS, we used the kainic acid (KA)-induced epilepsy animal model. SRS was monitored for 3 weeks after injection of a single convulsive dose of KA. KA-treated rats with SRS, KA-treated rats without SRS, and saline-treated rats were then measured in Morris water maze. In this spatial learning task, KA-treated rats with SRS performed poorer compared to those without SRS and those treated with saline. During the subsequent probe trials, KA-treated rats with SRS spent less swim path and time in the target quadrant but more swim path and time in the opposite quadrant, and showed fewer platform crossings. Moreover, in situ hybridization and immunohistochemistry showed that both ERG1/NSF mRNA and NSF immunoreactive expression were down-regulated in the CA1 and dorsal dentate gyrus cells (dDGCs) of the hippocampus, and interestingly, tyrosine hydroxylase (TH) immunoreactive dopamine (DA) neurons were lost in ventral tegmental area (VTA) in the KA rats with SRS. These data demonstrate that SRS impairs spatial learning memory and suggest that the down-regulation of NSF expression pattern in the hippocampus and the loss of DA neurons in VTA might contribute to the spatial learning memory deficits induced by SRS.

Animals↗

PubMed1989

Elevated dynorphin in the hippocampal formation of aged rats: relation to cognitive impairment on a spatial learning task.

Radioimmunoassay revealed increased dynorphin A(1-8)-like immunoreactivity [dynA(1-8)LI] in the aged rat brain. Among a number of brain regions examined, an age-related dynA(1-8)LI elevation was found only in the hippocampal formation and frontal cortex. Moreover, the increase in dynA(1-8)LI in the aged hippocampus was associated with a decline in spatial learning ability: dynA(1-8)LI distinguished aged rats that were behaviorally impaired from aged cohorts that learned the spatial task as rapidly as younger animals. Northern blot hybridization using a 32P-labeled complementary RNA probe encoding rat prodynorphin indicated that the abundance of prodynorphin mRNA was also significantly increased in the hippocampal formation of aged rats with identified spatial learning impairments.

Aging↗

PubMed1997

Dose-related impairment of spatial learning by intrahippocampal scopolamine: antagonism by ondansetron, a 5-HT3 receptor antagonist.

To study the role of hippocampal muscarinic receptors in spatial learning, various doses of scopolamine were injected bilaterally into the CA1 region of the dorsal hippocampus of rats trained in a two-platform spatial discrimination task. Scopolamine administered 10 min before each training session at doses ranging from 3.75 to 15 micrograms/microliter impaired choice accuracy, had no effect on choice latency and increased the errors of omission only with 7.5 micrograms on day 1 and with 15 micrograms on days 1 and 2 of training. No dose affected choice accuracy or latency of a non-spatial visual discrimination task. A subcutaneous dose of 1 microgram/kg ondansetron, a 5-HT3 receptor antagonist, 30 min before each training session prevented the impairment of choice accuracy by intrahippocampal 3.75 micrograms scopolamine but 0.1 microgram/kg ondansetron had no such effect. No dose of ondansetron by itself modified the acquisition of spatial learning. The results suggest that relatively low doses of scopolamine in the dorsal hippocampus selectively impair the acquisition of a spatial discrimination task, and that blockade of 5-HT3 receptors prevents the deficit caused by the muscarinic antagonist. The utility of the deficit of spatial learning induced by intrahippocampal scopolamine for modelling some aspects of memory disturbances in Alzheimer's disease is discussed.

Animals↗

PubMed1995

Effects of ibogaine on sensory-motor function, activity, and spatial learning in rats.

Ibogaine, a naturally occurring alkaloid, has been show to reduce naloxone-precipitated withdrawal symptoms from morphine. Given the clinical possibilities, it is important to determine ibogaine's effects on sensory-motor function, activity, learning, and memory. Long-Evans rats injected with doses of 20-60 mg/kg of ibogaine displayed slower response times on sensory and sensory-motor tests and were impaired in performing specific motor reflexes at doses of 40-60 mg/kg. Furthermore, these rats showed a marked reduction in locomotor and nonlocomotor activity, as well as emotionality at doses ranging from 10-40 mg/kg. At the higher doses the rats appeared to be virtually inactive. There were also deficits in learning a spatial location task (a dry-land version of the Morris water-maze). The deficits, however, were probably due to a reduction in locomotor activity and reduction in detection of sensory information. In a final experiment, a single injection of 40 mg/kg of ibogaine had marked deleterious effects on the acquisition of the spatial location task 1 but not 7 days after the injection, even though in this case there were no effects on sensory motor function 1 or 7 days after the injection. Thus, there are severe sensory-motor activity and learning problems while the animal is under the influence of ibogaine (acute effect) as well as long-term consequences on learning without concomitant changes in sensory-motor function.

Animals↗

PubMedDate not supplied

Effects of aging on spatial learning and hippocampal protein kinase C in mice.

C57BL/6Nia and F1(B6xD2)Nia mice were tested on the Morris water maze task for 5 days followed by 12 days of testing on the place learning-set task (8 trials/day with each task). Mice were tested at 3, 14, and 25 months of age. C57 mice, 25 months of age, were significantly impaired in both the Morris and place learning-set task probe trial performance compared to mice 3 months of age (p < 0.05). These aged C57 mice also demonstrated a significant reduction in membrane-bound hippocampal protein kinase C (PKC) activity (p < 0.05) with no significant change in cytosolic PKC activity. F1 mice, however, showed no effect of age on probe trial performance on the spatial learning tasks. In addition, in a comparison of C57 and F1 mice within each age group, F1 mice demonstrated superior learning performance which was accompanied by a significant elevation in PKC activity (p < 0.05). Spatial learning performance of both strains significantly correlated with membrane-bound PKC activity (p < 0.01). These data provide additional support for our previous hypothesis of an involvement of hippocampal PKC activity in spatial learning and suggest that the amount of membrane-bound PKC activity may be a determinant of age-related decline in spatial learning.

Aging↗

PubMedDate not supplied

Impairment of spatial learning following preweaning cocaine exposure in the adult rat.

The present investigation focuses on learning and working memory capabilities of adult male and female Sprague-Dawley rats that were exposed to either cocaine (50 mg/kg/day sc) or distilled water during infancy (postnatal days 11-20). Learning and memory were assessed at 4 months using the eight-arm radial maze. Training was carried out in three phases in order to separate procedural learning from spatial capacity. Once criterion (entering at least seven arms without repeating arms for four out of five trials) was achieved in the first training room (Room 1), testing was moved to a second room (Room 2) with unique visual cues and an identical maze. Upon reaching criterion in Room 2, animals were returned to Room 1 and examined again. Cocaine-pretreated rats were less accurate than vehicle-pretreated rats during the first 10 trials of training. During the first five trials in Room 2 cocaine-pretreated animals made more errors, and made errors earlier within trials, than the vehicle-pretreated animals. Upon return to Room 1, reliable Gender x Pretreatment interactions were found for errors and total arms entered. These data demonstrate that a brief period of postnatal cocaine exposure can impair spatial cognition in adulthood and tentatively suggest that females are more sensitive than males.

Aging↗

PubMed1997

The medial supramammillary nucleus, spatial learning and the frequency of hippocampal theta activity.

Previous studies have shown that the presence of hippocampal theta activity (theta) is important for learning and that the medial supramammillary nucleus (SuM) is involved in the control of the frequency of theta. In the present experiments, a single-day version (20 trials) of the Morris water maze was used to investigate the effects of drug injections into SuM on hippocampal theta frequency and spatial learning. Two groups of rats received an injection of chlordiazepoxide (CDP, 0.5 microl, 40 microg/microl) or saline (0.5 microl) into SuM 10 min before training in the Morris water maze. Two other groups of rats received an i.p. injection of 5 mg/kg CDP or saline, and two further groups received short (10 min) or long (15 min) immersion in cool water (22 degrees C) before training. The results showed: (1) in all groups theta frequency was an inverse logarithmic function of training time; (2) systemic CDP or long cool water exposure decreased theta frequency to a greater extent (by 1 Hz), and also impaired learning to a greater extent, than the other treatments; (3) that SuM-CDP produced a modest decrease in theta frequency (0.35-0.5 Hz) and a modest impairment of spatial learning. These data suggest that theta frequency per se may be important for spatial learning and that total abolition of theta is not necessary for dysfunction; and that while a lesser part of the effect of i.p. CDP on spatial learning appears to be mediated by SuM the greater part appears to involve other nuclei as well.

Amino Acid Sequence↗

PubMed2005

Caffeine improves spatial learning deficits in an animal model of attention deficit hyperactivity disorder (ADHD) -- the spontaneously hypertensive rat (SHR).

The spontaneously hypertensive rat (SHR) is generally considered to be a suitable genetic model for the study of attention deficit hyperactivity disorder (ADHD), since it displays hyperactivity, impulsivity, poorly sustained attention, and deficits in learning and memory processes. Converging evidence suggests a primary role of disturbance in the dopaminergic neurotransmission in ADHD patients and in SHR, and in addition, some studies have also demonstrated alterations in adenosinergic neurotransmission in SHR. In the present study, adult female Wistar (WIS) and SHR rats received caffeine (1-10 mg/kg i.p.) 30 min before training, immediately after training, or 30 min before a test session in the spatial version of the Morris water maze. The effect of caffeine administration on WIS and SHR blood pressure was also measured. SHR needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of WIS rats in the test session (48 h later), demonstrating a selective deficit in spatial learning. Pre-training administration of caffeine (1-10 mg/kg i.p.) improved this spatial learning deficit in SHR, but did not alter the WIS performance. In contrast, post-training administration of caffeine (3 mg/kg i.p.) did not alter the SHR test performance, but increased memory retention in WIS rats. No dose of caffeine tested altered the mean blood pressure of WIS or SHR. These results demonstrate a selective spatial learning deficit in SHR which can be attenuated by pre-training administration of caffeine. In addition, the present findings indicate that the spatial learning deficit in SHR is not directly related to hypertension.

Animals↗

PubMed2005

Contributions of the mitogen-activated protein kinase and protein kinase C cascades in spatial learning and memory mediated by the nucleus accumbens.

Several studies have reported a role for the nucleus accumbens (NAcc) in learning and memory. Specifically, NAcc seems to function as a neural bridge for the translation of corticolimbic information to the motor system mediating locomotor learning, but the signaling mechanisms involved in this striatal learning await further investigation. The present experiments investigated the role of the mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) cascades within the NAcc of Long-Evans rats in a food-search spatial learning task (FSSLT). First, we used immunoblotting to examine changes in MAPK p42/p44 phosphorylation within the NAcc in the acquisition phase of the FSSLT. Second, we examined the effect on the acquisition and retention phases in the FSSLT of pretraining intra-accumbal microinjections of the MAPK [U0126; 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene, 1 microg/side] or PKC [GF109203X; bisindolylmaleimide or 1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl) maleimide, 0.5 ng/side] inhibitors (four training sessions; one session/day). Third, the potential coupling of PKC and MAPK signaling pathways in the NAcc in spatial learning was studied using microinjections of GF109203X, radioactive activity assays, and immunoblotting. Results showed that 1) MAPK p42/p44 phosphorylation is augmented within the NAcc after spatial learning, 2) MAPK and PKC inhibition caused differential deficits in the acquisition and formation of spatial memories, and 3) inhibition of PKC activity by GF109203X caused a reduction in MAPKs phosphorylation in the NAcc in an early stage of the acquisition phase. Overall, these findings suggest that NAcc-PKC and -MAPK play important roles in spatial learning and that MAPKs phosphorylation seems to be mediated through the activation of the PKC signaling pathway.

Animals↗

PubMed1999

Aging and corticosterone injections affect spatial learning in Fischer-344 X Brown norway rats.

The hippocampus is one of the first brain structures to show age-related changes. Moreover, hippocampal neurons are endangered by prolonged exposure to high circulating levels of corticosterone with stress or aging. We examined the effects of aging and high corticosterone levels on spatial learning, a key hippocampal function. Young (4-6 months), old (23-25 months), and very old (31 months) male Fischer-344xBrown Norway (F-344xBN) rats received six pre-testing days in the Morris water task to determine baseline spatial learning performance. Next, half the animals in each group were given daily corticosterone injections for 15 days. During the last six injection days, all animals underwent post-testing in the Morris water task with the environment and goal location changed. Baseline, peak, and clearance plasma corticosterone levels were determined. During pre-testing, old animals swam as directly to the goal as the young, but very old animals were significantly impaired. During post-testing, both old and very old non-injected animals had significantly greater directional heading errors and flatter learning curves than the young. Among injected animals, the very old performed as well as the young, but the old did not. Old animals who did not show improvement during the first three pre-testing days were responsible for the old impairment during post-testing. Thus, only very old F-344xBN rats are impaired when initially exposed to a spatial learning task, but half the old and all very old animals are impaired when the environment is changed. Very old F-344xBN rats, however, demonstrate enhanced spatial learning when exposed to corticosterone injections.

Age Factors↗

PubMed2006

Interleukin-1beta induces anorexia but not spatial learning and memory deficits in the rat.

Sickness behaviors are a set of adaptive responses to infection that include lethargy, anorexia, and, of direct relevance to this work, learning and memory impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1beta) has been proposed as the primary peripheral mediator of these sickness behaviors, though few studies have investigated the effects of peripheral IL-1beta on learning and memory. We used three different versions of the Morris water task (Morris water task), a spatial learning and memory task, to separately assess the effects of peripheral IL-1beta on acquisition, consolidation, and retention of spatial location information. Using a dose that induced anorexia, assessed as a significant reduction in body weight, we observed no performance impairments in the IL-1beta-treated rats across the different versions of the task, suggesting that peripheral IL-1beta alone is insufficient to induce spatial learning and memory impairments in the rat. The observed dissociation of anorexia and cognitive dysfunction suggests that, either spatial learning and memory are not principal components of the sickness response, or cognitive dysfunction requires different or additional peripheral mediator(s).

Analysis of Variance↗

PubMed1996

Sexually dimorphic spatial learning in meadow voles Microtus pennsylvanicus and deer mice Peromyscus maniculatus.

A number of studies examining developmental, neural and hormonal aspects of sexually dimorphic spatial learning (Morris water-maze) in meadow voles (Microtus pennsylvanicus) and deer mice (Peromyscus maniculatus) are described. We found that, in adult deer mice, female spatial performance decreased during the breeding season relative to the non-breeding season, whereas the reverse pattern was observed in male performance. There was a sex difference favouring males in spatial learning during the breeding season, but not during the non-breeding season. In adult meadow voles, females with low levels of oestradiol and males performed better in the water-maze than females with high levels of oestradiol. Postweaning voles (20 and 25 days after birth) acquired the water-maze task more quickly than preweaning voles (day 10). No sex difference in water-maze performance was evident at any of these juvenile ages. When these same voles were tested again as adults to investigate retention and re-acquisition of the water-maze, both males and females from male-biased litters re-acquired the task better than males and females from female-biased litters. Together, the results of these studies indicate that sexually dimorphic spatial ability is dependent on the organization (in utero) and activational effects of gonadal hormones. These studies provide the first demonstration of the influence of natural changes in reproductive status on spatial learning of deer mice and meadow voles. The results also demonstrate that spatial performance of males and females is differentially affected by changes in reproductive status and that group differences in the laboratory are associated with group differences in space utilization in the wild. These findings help to clarify previous apparently contradictory findings about sex differences in spatial ability.

Animals↗

PubMed1990

Effects of haloperidol on recall and information processing in verbal and spatial learning.

1. Normal male subjects were tested with either a multi-trial word list learning test or a spatial analogue prior to administration of either 4 mg. or 10 mg. of oral haloperidol. Six hours after drug administration subjects who had previously received the verbal test were administered the spatial test, and vice versa, so for each test there was a no-drug control group, a group tested after receiving 4 mg. of haloperidol, and a group tested after a 10 mg. dose. 2. Both the verbal and spatial learning tests yield multidimensional measures of components of memory and learning, including measures sensitive to effort-demanding and more automatic information processing operations. 3. Results showed no differences for either test among the pre-drug control group and the 4 mg. and 10 mg. groups, with only one minor exception. 4. The lack of significant results cannot be attributed to insensitivity of the test instruments used, since previous studies have documented sensitivity to a number of clinical conditions and to aging. 5. Results have implications regarding clinical effects of haloperidol. A theory that links dopaminergic functioning with effortful information processing underlying memory and learning was not supported.

Adult↗

PubMed2002

Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility.

Creatine kinases are important in maintaining cellular-energy homeostasis, and neuroprotective effects have been attributed to the administration of creatine and creatine-like compounds. Herein we examine whether ablation of the cytosolic brain-type creatine kinase (B-CK) in mice has detrimental effects on brain development, physiological integrity or task performance. Mice deficient in B-CK (B-CK-/-) showed no gross abnormalities in brain anatomy or mitochondrial ultrastructure, but had a larger intra- and infrapyramidal mossy fibre area. Nuclear magnetic resonance spectroscopy revealed that adenosine triphosphate (ATP) and phosphocreatine (PCr) levels were unaffected, but demonstrated an apparent reduction of the PCr left arrow over right arrow ATP phosphorus exchange capacity in these mice. When assessing behavioural characteristics B-CK-/- animals showed diminished open-field habituation. In the water maze, adult B-CK-/- mice were slower to learn, but acquired the spatial task. This task performance deficit persisted in 24-month-old, aged B-CK-/- mice, on top of the age-related memory decline normally seen in old animals. Finally, a delayed development of pentylenetetrazole-induced seizures (creating a high-energy demand) was observed in B-CK-/- mice. It is suggested that the persistent expression of the mitochondrial isoform ubiquitous mitochondrial CK (UbCKmit) in the creatine/phospho-creatine shuttle provides compensation for the loss of B-CK in the brain. Our studies indicate a role for the creatine-phosphocreatine/CK circuit in the formation or maintenance of hippocampal mossy fibre connections, and processes that involve habituation, spatial learning and seizure susceptibility. However, for fuelling of basic physiological activities the role of B-CK can be compensated for by other systems in the versatile and robust metabolic-energy network of the brain.

Animals↗

PubMedDate not supplied

Chronically increased Gsalpha signaling disrupts associative and spatial learning.

The cAMP/PKA pathway plays a critical role in learning and memory systems in animals ranging from mice to Drosophila to Aplysia. Studies of olfactory learning in Drosophila suggest that altered expression of either positive or negative regulators of the cAMP/PKA signaling pathway beyond a certain optimum range may be deleterious. Here we provide genetic evidence of the behavioral and physiological effects of increased signaling through the cAMP/PKA pathway in mice. We have generated transgenic mice in which the expression of a constitutively active form of Gsalpha (Gsalpha* Q227L), the G protein that stimulates adenylyl cyclase activity, is driven in neurons within the forebrain by the promoter from the CaMKIIalpha gene. Despite significantly increased adenylyl cyclase activity, Gsalpha* transgenic mice exhibit PKA-dependent decreases in levels of cAMP due to a compensatory up-regulation in phosphodiesterase activity. Interestingly, Gsalpha* transgenic mice also exhibit enhanced basal synaptic transmission. Consistent with a role for the cAMP/PKA pathway in learning and memory, Gsalpha* transgenic mice show impairments in spatial learning in the Morris water maze and in contextual and cued fear conditioning tasks. The learning deficits observed in these transgenic mice suggest that associative and spatial learning requires regulated Gsalpha protein signaling, much as does olfactory learning in Drosophila.

Adenylyl Cyclases↗