Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Spatial Learning”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed2001

Learning impairments and motor dysfunctions in adult Lhx5-deficient mice displaying hippocampal disorganization.

Lhx5 is a member of the LIM homeobox gene family that regulates development of the nervous system. Adult mice generated with a mutation in Lhx5 were found to display absent or disorganized hippocampal neuroanatomy. The pyramidal cell layer in Ammon's horn and the granule cell layer in the dentate gyrus were absent or poorly defined in the hippocampus of adult Lhx5 knockout mice. Behavioral phenotyping of Lhx5 null mutants detected deficits on learning and memory tasks, including the Barnes maze spatial learning task, spontaneous alternation recognition memory, and contextual and cued fear conditioning. General health, neurological reflexes, and sensory abilities appeared to be normal in Lhx5 knockout mice. Motor tests showed impaired performance on some measures of motor activity, coordination, balance, and gait. These results reveal functional outcomes of Lhx5 gene deletion on the integrity of hippocampal neuroanatomy and behavior in the adult mouse.

Animals↗
PubMed1998

Behavioural, neurochemical and neuroanatomical effects of chronic postnatal N-nitro-L-arginine methyl ester treatment in neonatal and adult rats.

In the present study we evaluated the consequences of interference with nitric oxide synthesis during development on brain function and behaviour in later life. Rat pups received a daily injection of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg, s.c.) from postnatal day 0 to 24. At postnatal day 8 L-NAME-treated rats had enlarged and heavier stomachs, while body weights appeared to be reduced. The stomachs were not affected in size and weight anymore at postnatal day 24, whereas the body weights were still reduced by the L-NAME treatment, although they soon recovered after termination of the treatment. At four months-of-age, rats were tested in non-cognitive (open field) and cognitive (Morris water escape, two-way active avoidance) tasks. Open field behaviour of adult rats postnatally treated with L-NAME was not affected. In the water escape task there were no differences between the saline and L-NAME-treated rats in spatial discrimination learning and spatial reversal learning. Furthermore, postnatal L-NAME treatment did not have an effect on the acquisition of the two-way active avoidance task. Subsequently, we tested rat pups during the L-NAME treatment at postnatal day 19 through 24 in the open field and the two-way active avoidance task. L-NAME treatment appeared to increase the behavioural activity in the open field. There was no difference in behaviour in the active avoidance task between saline and L-NAME-treated rats. Biochemical and immunocytochemical studies showed that at postnatal day 8 the basal cyclic GMP level was reduced, while the cyclic GMP formation due to incubation with the nitric oxide donor sodium nitroprusside appeared to be increased in the hippocampus, striatum and frontal cortex of L-NAME-treated rats. Hence, nitric oxide synthase was inhibited whereas the soluble guanylyl cyclase activity may be increased in sensitivity. At postnatal day 24 basal cyclic GMP levels and nitric oxide-mediated cyclic GMP formation in the brain structures of L-NAME-treated rats had normal values again. Taken together, the findings of this study suggest that postnatal inhibition of nitric oxide synthase has profound neurochemical effects during development and may have short-lasting effects on non-cognitive behaviour, but it does not affect behaviour and brain function in later life.

Animals↗
PubMed2001

Genetic evidence for noradrenergic control of long-term memory consolidation.

Memory formation involves dynamic interactions among many brain structures and their linking pathways. The noradrenaline (NA) system in the CNS plays an important role in a wide variety of neurological and psychological functions. Alteration in the NA system is implicated in the pathological states of some neuropsychiatric disorders. Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines. The regulatory mechanism of the TH reaction is generally considered to play a key role in controlling the catecholaminergic actions. Mice heterozygous for the mutation of the gene encoding TH exhibit the reduced TH activity in tissues. These mice have a moderate reduction in NA accumulation and release in brain regions. The mutant mice exhibit deficits in the water-finding task associated with latent learning performance, suggesting the impairment in memory formation. Spatial learning performance measured by the water maze task is normal in the mutants. However, they display deficits in long-term memory formation of conditioned learning evaluated with three distinct behavioral paradigms, including active avoidance, cued fear conditioning, and conditioned taste aversion, without affecting short-term memory. These memory deficits are restored by the drug-induced stimulation of NA activity at the postconditioning phase. Analysis of the mutant mice indicates that the central NA system is essential for the consolidation process in long-term memory of conditioned learning. The process appears to be implicated in the NA activity in the cerebral cortex and/or amygdaloid complex.

Amygdala↗
PubMed2005

Defective place cell activity in nociceptin receptor knockout mice with elevated NMDA receptor-dependent long-term potentiation.

There is growing evidence that NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus mediates the synaptic plasticity that underlies spatial learning and memory. LTP deficiencies correlate well with spatial memory deficits and LTP enhancements may improve spatial memory. In addition, LTP deficiencies are associated with abnormal place cells as expected from the spatial mapping hypothesis of hippocampal function. In contrast, nothing is known on how enhanced NMDA receptor-dependent LTP affects place cells. To address this question we recorded place cells from mice lacking the nociceptin receptor (NOP1/ORL1/OP4) that have enhanced hippocampal LTP. We found that the enhanced LTP was mediated by NMDA receptors, did not require L-type calcium channels, and occurred only when high frequency tetanizing stimulus trains were used. Place cells in nociceptin receptor knockout mice were abnormal in several ways: they were less stable, had noisier positional firing patterns, larger firing fields and higher discharge rates inside and outside the firing fields. Our results suggest that excessive LTP can cause subnormal hippocampal place cell function. The effects of LTP enhancement on place cell function may therefore also depend on molecular details of synaptic plasticity, including the relationship between stimulus frequency and synaptic strength, and not merely on the magnitude of synaptic strength increases. The data have important clinical implications on development of strategies to improve cognitive function.

Action Potentials↗
PubMed1992

Functional changes implicating dopaminergic systems following perinatal treatments.

A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-hydroxydopamine (6-OHDA) (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound, or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphetamine-induced activity. It was shown that prenatal metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d-amphetamine-induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded according to the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine-induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85% depletion compared to control values) caused notable impairments. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered.

Animals↗
PubMedDate not supplied

[Maternal methyl-containing dietary supplementation alters the ability to learn in adult rats in swimming Morris test].

Maternal choline diet influences the spatial learning processes. In this work, the learning ability of adult progeny of mothers who had received methyl diet enriched with choline and betain during pregnancy and lactation was studied in Morris test. The introduction of the diet to pregnant rats resulted in an increase in the time of search for invisible platform and time of swimming near the pool walls in offsprings, which meant a worsening of their learning ability. It was also found that change in platform searching strategy was not associated with an increase in anxiety of male rats. Possible involvement of maternal methyl diet in the change of expression of genes which control development of the nervous system is discussed.

Animals↗
PubMed2003

Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date.

The hippocampal formation, to which new neurons are added on a daily basis throughout life, is important in spatial learning. Surviving de novo produced cells integrate into the functional circuitry, where they can influence both normal and pathological behaviors. In this study, we examined the effect of the water-maze (a hippocampal-dependent spatial task) on neurogenesis. Learning in this task can be divided into two phases, an early phase during which performance improves rapidly, and a late phase during which asymptotic levels of performance are reached. Here we demonstrate that the late phase of learning has a multifaceted effect on neurogenesis depending on the birth date of new neurons. The number of newly born cells increased contingently with the late phase and a large proportion of these cells survived for at least 4 weeks and differentiated into neurons. In contrast, late-phase learning decreased the number of newly born cells produced during the early phase. This decline in neurogenesis was positively correlated with performance in the water-maze. Thus, rats with the highest de novo cell number were less able to acquire and use spatial information than those with low numbers of new cells. These results show that learning has a complex effect on hippocampal neurogenesis, and reveals a novel mechanism through which neurogenesis may influence normal and pathological behaviors.

Aging↗
PubMed1997

Impaired place learning and unimpaired cue learning in hippocampal-lesioned pigeons.

Hippocampal processing is often crucial for normal spatial learning and memory in both birds and mammals, suggesting a general similarity in avian and mammalian hippocampal function. However, few studies using birds have examined the effect of hippocampal lesions on spatial tasks analogous to those typically used with mammals. Therefore, we examined how hippocampal lesions would affect the performance of pigeons in a dry version of the water maze. Experiment 1 showed that hippocampal-lesioned birds were impaired in acquiring the location of hidden food in the maze. Experiment 2 showed that hippocampal-lesioned birds were not impaired when a single cue indicated the location of hidden food. These results support the notion that avian and mammalian hippocampal functions are quite similar, in terms of the tasks for which their processing is crucial and the tasks for which it is not.

Animals↗
PubMed2006

Repetitive dextromethorphan at adolescence affects water maze learning in female rats.

Effects of repetitive dextromethorphan at adolescence on a spatial learning of rats were investigated. Rats received 10 daily injections of dextromethorphan (40 mg/kg) from postnatal day 28 thru 37, and were then subjected to the Morris water maze task from day 38. Significant impairments were found in the probe trial and the reversal training of the maze learning in the female rats, but not in males, treated with dextromethorphan. This result suggests that repetitive dextromethorphan, that is, abuse of dextromethorphan, at adolescence may induce deficits in the hippocampus-based memory function, perhaps more obviously in females.

Age Factors↗
PubMed1994

Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice.

Age-related changes in spatial learning performance were studied in relation to acetylcholine (ACh) content of brain regions in male aged (28-month-old) and young (5-month-old) mice of BDF1 strain. As there were large individual differences in the spatial performance of aged mice, the aged mice were divided into two subgroups, old A and old B. The old A group included the six best performers out of the 12 aged mice and the old B group included the remaining 6 worst performers. In a radial-arm maze task with 8 baited arms, aged mice in the old B group showed a marked deficit in acquisition performance and habituation to the apparatus. In the more difficult maze task with only 4 baited arms, the aged mice in the old B group exhibited marked impairment both in working memory and reference memory throughout training, whereas the aged mice in the old A group showed deficits in reference memory during the first 20 days of training and working memory during the last 20 days relative to young mice. Neurochemical analysis revealed significant decreases in the ACh content of the hippocampus and striatum in both aged groups, and in the frontal cortex and posterior cortex of the old B group as compared to the young group. Correlational analysis showed significant correlations between learning performance in the spatial task and ACh levels in the hippocampus, frontal cortex, and posterior cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

A genetic test of the effects of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning.

Using a genetic approach, we assessed the effects of mutations in protein kinase A (PKA) on long-term potentiation (LTP) in the mossy fiber pathway and its relationship to spatial and contextual learning. Ablation by gene targeting of the C beta 1 or the RI beta isoform of PKA produces a selective defect in mossy fiber LTP, providing genetic evidence for the role of these isoforms in the mossy fiber pathway. Despite the elimination of mossy fiber LTP, the behavioral responses to novelty, spatial learning, and conditioning to context are unaffected. Thus, contrary to current theories about hippocampal function, mossy fiber LTP does not appear to be required for spatial or contextual learning. In the absence of mossy fiber LTP, adequate spatial and contextual information might reach the CA1 region via other pathways from the entorhinal cortex.

Animals↗
PubMed2005

Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory.

Regulated proteolysis by the ubiquitin pathway has been implicated in control of the cell cycle, transcriptional activation, cell fate and growth, and synaptogenesis. The ubiquitin-proteasome system is involved in synaptic plasticity and is proposed to be part of a molecular switch that converts short-term synaptic potentiation to long-term changes in synaptic strength. In Aplysia, a component of the ubiquitin system termed ubiquitin C-terminal hydrolase (Ap-Uch) has been shown to be essential for long-term facilitation. To examine whether Uch plays a role in learning, memory, and synaptic plasticity in mammals, we have analyzed mice homozygous for a targeted mutation in ubiquitin C-terminal hydrolase L3 (Uchl3), an orthologue of Ap-Uch. Mice homozygous for the mutation in Uchl3 are viable, with no obvious developmental, histological, or fertility abnormalities. We demonstrate that Uchl3-/- mice have a significant learning deficit relative to wild type littermates in the spatial version of the Morris water maze and the 8-arm radial maze. Further, the impaired performance in the 8-arm radial maze of Uchl3-/- mice is due to significantly increased working memory errors. Examination of hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to underlie memory storage, revealed no significant differences in LTP in hippocampal slices from Uchl3-/- mice. Our results suggest a novel role for ubiquitin C-terminal hydrolase enzymes in mammals in spatial learning and working memory.

Animals↗
PubMed2005

Complex-environment rearing prevents prenatal hypoxia-induced deficits in hippocampal cellular mechanisms necessary for memory consolidation in the adult Wistar rat.

Hypoxic episodes in utero can result in enduring and debilitating neurological sequelae that include nonprogressive motor disorders and/or significant learning deficits. The extent of long-term disruption of synaptic function following prenatal hypoxia and its subsequent effect on learning ability, however, remain to be established. Polysialylation of the neural cell adhesion molecule, a cellular event integral to the consolidation of diverse learning paradigms, was used to correlate cellular end points with learning deficits as a consequence of prenatal hypoxia. Pregnant Wistar dams exposed to hypobaric hypoxia during gestational days 10-20 had significantly reduced litter sizes, but the lack of effect on subsequent pup weight gain suggested no gross developmental deficit. By contrast, adult animals with prior in utero hypoxia exhibited significant learning difficulties in both acquisition of a water maze spatial learning task and recall of a passive avoidance paradigm. Learning deficits correlated with a significant reduction in the frequency of polysialylated neurons in the dentate infragranular zone and a blunting of their transient activation 12 hr following task acquisition. Rearing animals with prior prenatal hypoxia in a complex environment, however, eliminated the task acquisition and recall deficits and restored dentate polysialylated cell frequency and their transient posttraining increase.

Animals↗
PubMed2006

Chlordiazepoxide and dizocilpine, but not morphine, selectively impair acquisition under a novel repeated-acquisition and performance task in rats.

RATIONALE: Some classes of drugs can selectively affect learning (i.e., acquisition of behavior) at doses that do not affect performance (i.e., previously learned behavior). Some drugs (e.g., benzodiazepines) show selective effects on acquisition across a wide variety of tasks. Other drugs [e.g., N-methyl-D-aspartate (NMDA) antagonists and opiate agonists], however, show selective effects under some tasks, but not others. OBJECTIVES: The purpose of this study was to examine the effects of the NMDA-antagonist dizocilpine (0.01-0.3 mg/kg), the opiate-agonist morphine (1.0-17.0 mg/kg), and the benzodiazepine chlordiazepoxide (3.0-30.0 mg/kg) in rats under a novel repeated-acquisition and performance task. METHODS: Nose pokes to a correct location within a 2x3 stimulus array on a computer touch screen were reinforced with food. In the acquisition component, the correct location changed across sessions but remained constant within sessions; in the performance component, the correct location was constant both across and within sessions. RESULTS: Both chlordiazepoxide and dizocilpine selectively impaired accuracy in the acquisition component at doses that did not affect accuracy in the performance component or overall response speed. Morphine, however, did not affect acquisition without affecting performance or response speed. CONCLUSIONS: These results with rats resembled those previously obtained for response-sequence learning in primates, rather than those previously reported for spatial learning in rats. Therefore, previous discrepancies in results for NMDA antagonists and opiate agonists across tasks probably were not a function of the species studied, but, rather, they more likely were a function of unique variables controlling acquisition within each task.

Animals↗
PubMed1993

The aged mouse as a model of cognitive decline with special emphasis on studies in NMRI mice.

The use of the aged mouse as an integrated model of age-related cognitive decline is reviewed, with special emphasis on experiments covering the life span of NMRI mice, using different age-groups ranging from 3 through to 22 months. Age-related changes in the sensorimotor profile, spontaneous behaviour and performance in learning and memory tasks are considered. The data provide evidence for cognitive impairment and decreases in spontaneous activity and exploration from middle age onwards. Chronologically, this age depends on the longevity of the strain selected; in NMRI mice, middle age corresponds to 11-12 months. Complex learning tasks, such as the Morris water maze for spatial learning, appear to be the most sensitive to age-related changes, as are tests requiring prolonged retention of acquired information, for example, using passive avoidance. Cued and simple discrimination learning are only impaired in the oldest animals. Age-related changes in non-cognitive variables, including sensorimotor capacity, pain sensitivity, emotionality, or locomotor activity, do not account for the learning impairments, although deficits in visual acuity cannot be excluded in the very old animals. Detailed analysis of the individual data for middle aged and old mice, using discriminant and correlation studies highlight a marked heterogeneity between animals of any given chronological age. Furthermore, individual aged mice do not exhibit similar degrees of impairment across all the behavioural variables, showing that aging is not a uniform process. The possible relationship between age-related behavioural decline and neurochemical changes is an area as yet unexplored apart from a few isolated investigations, including a study on ChAT and AChE in NMRI mice. The studies in the NMRI mice illustrate the value of investigating the full age-range to detect an age group which shows cognitive decline dissociable from physical or emotional changes and which is representative of the population as a whole.

Aged↗
PubMed2000

Sexually dimorphic cognitive style in rats emerges after puberty.

In a water maze (WM), rats employ different and sexually dimorphic behavioral strategies to solve a place-learning task, a test of cognitive/propositional ability. Puberty is the last step in brain development and marks an important phase with regard to sexually dimorphic cognitive performance and behavior. The present study assessed possible sex differences in cognitive style before and after puberty in a WM place-learning task. Since nitric oxide (NO) is implicated in spatial learning and hippocampal function, and since brain NO(-)(2) + NO(-)(3) levels (stable metabolites of NO) display region-specific sex differences in rat brain, NO(-)(2) + NO(-)(3) levels were determined after behavioral testing. The sex-related style difference emerged very clearly but only in the adult rats, which suggests that the female behavioral strategy in the WM place-learning task requires the presence of female sex hormones at puberty. Although NO(-)(2) + NO(-)(3) levels were higher in the adult rats and males compared to prepubertal and female rats, respectively, no significant correlations emerged between brain NO and behavior. The fact that the behavioral sexually dimorphic cognitive-style effect observed here and in previous studies appears to emerge only after puberty suggests that awareness of such postpubertal sex differences may also be important in human educational and therapeutic contexts.

Adaptation, Psychological↗
PubMed1971

Pavlovian pattern learning by nonlinear neural networks.

This note describes laws for the anatomy, potentials, spiking rules, and transmitters of some networks of formal neurons that enable them to learn spatial patterns by Pavlovian conditioning. Applications to spacetime pattern learning and operant conditioning are then possible, if the conditioning is viewed as multi-channel Pavlovian conditioning in a highly inhomogeneous anatomy. In suitable anatomies, biases in learning because of axon collaterals with nonuniformly distributed diameters can be corrected if one properly couples the action potential to transmitter potentiation, and chooses signal velocity proportional to axon diameter. These anatomies can contain any number of cells. Anatomies exist in which patterns may be learned without their being practiced overtly, whereas persistent recall of old patterns without the learning of newly imposed patterns is impossible. Physiologically, this constraint has the trivial interpretation that signals from one cell to another first pass through the intervening synaptic knob. Mechanisms that control learning rates at times important to the network (e.g., reward and punishment times) can be discussed. Serial behavior like that described by Lashley is possible: this consists of sequential learning and performance of patterns faster than would be allowed by a motor-feedback control, at velocities influenced by arousal level, with the possibility of abrupt termination of performance if conflicting environmental demands arise. Analogs of pattern completion and mass action exist, as do phase transitions in memory (for some rate parameters and anatomies, memory is rigid, for others, it is plastic). The laws limit the ways in which these networks can be interconnected to yield specific discrimination, learning, memory, and recall capabilities.

Action Potentials↗
PubMed2005

Long-term retention and overshadowing of proximal and distal cues following habituation in an object exploration task.

The object displacement task is a popular tool used to investigate spatial learning and memory. However, little attention has previously been given to long-term retention of spatial information following habituation to this task. Furthermore, the role of both proximal and distal cues in this type of passive retention of spatial information is controversial. In Study 1, we examined habituation in the object displacement task across 4 days and examined reactivity to spatial change 7 days post-acquisition. We found that rats habituated rapidly to the environment and retained this environment for the 7 days. Furthermore, this experiment shows that both proximal and distal spatial cues are important in the encoding of the environment during object displacement learning task. In Study 2, we examined the effect of overshadowing and demonstrate that proximal visual spatial cues can overshadow distal spatial cues if a conflict arises between both set.

Animals↗