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At least 19 recordsLinked to original sources

Preserved configural learning and spatial learning impairment in rats with hippocampal damage.

This study was undertaken to compare the effect of hippocampal neurotoxic lesions in rats on two behavioral tasks, one a test of spatial learning, and the other an operant discrimination task that is acquired by forming nonspatial configural associations. Lesions of the hippocampus were made with microinjections of ibotenic acid. After postoperative recovery, rats were trained initially to locate a camouflaged escape platform in a water maze using distal spatial cues. Rats also were trained in the maze apparatus with a visible escape platform under conditions in which spatial information was made irrelevant to performance, i.e., cue learning. In an operant task, the same rats were then trained on a discrimination that included simultaneous feature positive and feature negative components (trial types XA+, A-, XB-, B+). After completion of this nonspatial configural learning task, rats received additional training in the water maze using a new platform location for spatial learning. To the extent that proficient performance in both the maze and operant tasks depends on a common function of the hippocampus, i.e., configural learning, the expectation was that hippocampal lesions would prove equally detrimental to performance in both tasks. Contrary to this expectation, lesioned rats were severely impaired in spatial learning but readily acquired the operant discrimination, even exhibiting some evidence of enhanced performance on this nonspatial configural learning task. Performance of the lesioned rats during cue training in the water maze was also enhanced relative to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Dissociable effects of selective lesions to hippocampal subsystems on exploratory behavior, contextual learning, and spatial learning.

Rats received excitotoxic lesions of different subsystems within the hippocampal system--either the hippocampus proper (cornu ammonis and dentate gyrus; hippocampal lesions) or the entorhinal cortex-subicular region (entorhinal lesions). Subsequently, their activity in an operant chamber was monitored both before and after footshock had been delivered (Experiment 1). Rats with hippocampal lesions showed enhanced activity before the delivery of footshock and reduced freezing after the delivery of shock. Rats with entorhinal lesions showed control levels of activity before the delivery of footshock and control levels of freezing after the delivery of footshock. Both types of lesion impaired spatial learning in a water maze (Experiment 2). These results suggest that the deficits arising from damage to the hippocampal system in contextual and spatial learning have different origins.

Animals↗

How medical students learn spatial anatomy.

Despite its importance in clinical tasks, spatial learning is poorly understood. We did a randomised, single-blind study on 146 medical students to assess the effectiveness of student-controlled multiple views on the spatial learning process. High spatial ability of the student, and self-directed examination of an object from multiple different perspectives improves spatial learning.

Adult↗

An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses.

The search for cellular correlates of learning is a major challenge in neurobiology. The hippocampal formation is important for learning spatial relations. A possible long-lasting consequence of such spatial learning is alteration of the size, shape, or number of excitatory synapses. The dendritic spine density is a good index for the number of hippocampal excitatory synapses. By using laser-scanning confocal microscopy, we observed a significantly increased spine density in CA1 basal dendrites of spatially trained rats when compared to nontrained controls. With unchanged dendritic length, the higher spine density reflects an increased number of excitatory synapses per neuron associated with spatial learning.

Animals↗

Representation of actions in rats: the role of cerebellum in learning spatial performances by observation.

Experimental evidence demonstrates that cerebellar networks are involved in spatial learning, controlling the acquisition of exploration strategies without blocking motor execution of the task. Action learning by observation has been considered somehow related to motor physiology, because it provides a way of learning performances that is almost as effective as the actual execution of actions. Neuroimaging studies demonstrate that observation of movements performed by others, imagination of actions, and actual execution of motor performances share common neural substrates and that the cerebellum is among these shared areas. The present paper analyzes the effects of observation in learning a spatial task, focusing on the cerebellar role in learning a spatial ability through observation. We allowed normal rats to observe 200 Morris water maze trials performed by companion rats. After this observation training, "observer" rats underwent a hemicerebellectomy and then were tested in the Morris water maze. In spite of the cerebellar lesion, they displayed no spatial defects, exhibiting exploration abilities comparable to controls. When the cerebellar lesion preceded observation training, a complete lack of spatial observational learning was observed. Thus, as demonstrated already for the acquisition of spatial procedures through actual execution, cerebellar circuits appear to play a key role in the acquisition of spatial procedures also through observation. In conclusion, the present results provide strong support for a common neural basis in the observation of actions that are to be reproduced as well as in the actual production of the same actions.

Animals↗

The effects of forced exercise on hippocampal plasticity in the rat: A comparison of LTP, spatial- and non-spatial learning.

Physical activity may have the potential to improve cognitive function. Here we show that forced treadmill-running results in selective improvements in hippocampal plasticity. Rats that underwent exercise training demonstrated enhanced expression of long-term potentiation in dentate gyrus and enhanced object recognition learning. Spatial learning in the Morris watermaze was unaffected by exercise. These changes were associated with an increase in expression of brain-derived neurotrophic factor in the dentate gyrus.

Analysis of Variance↗

Treatment with MDMA from P11-20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats.

RATIONALE: Previous studies in rats showed that postnatal day (P)11-20 exposure to +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) causes learning and memory deficits in adulthood. The emergence and permanence of these learning deficits are currently unknown. OBJECTIVE: This study was designed to investigate learning and memory deficits in adolescent (P30 or P40) and older (P180 or P360) rats exposed to MDMA from P11-20. MATERIALS AND METHODS: Within each litter half the animals were exposed to MDMA (20 mg/kg) and half to saline (SAL) twice a day (8 h apart) from P11-20. In experiment (exp) 1, behavioral testing began on either P30 or P40, whereas in exp 2, testing began on either P180 or P360. Offspring were tested in the Cincinnati water maze (CWM), a test of path integration learning (2 trials/day for 5 days), and the Morris water maze (MWM) (three phases, with 5 days of 4 trials/day and a probe trial on the sixth day per phase). RESULTS: MDMA-treated rats took longer to find the platform and traveled a greater distance to find the platform at all ages tested in all phases of the MWM. MDMA-treated animals also spent less time in the target quadrant during probe trials. In the CWM, P30 and P40 animals took longer to find the goal and committed more errors in locating the goal, while P180 and P360 MDMA-treated animals performed similarly to SAL-treated animals. CONCLUSION: The data suggest that the spatial learning and memory deficits induced by MDMA are long lasting, while the path integration deficits recover over time.

Age Factors↗

Hippocampal map realignment and spatial learning.

The spatial selectivity of hippocampal neurons suggests that they contribute to an internal representation of current location. The activity of hippocampal pyramidal cells was recorded while adult (10-13 months old) and aged (24-28 months old) rats performed a task in which two spatial reference frames were put in conflict. Rats attempted to find an unmarked goal whose position was fixed relative to only one of the two reference frames. The ability of a rat's hippocampus to adjust to the conflicting information and use the 'correct' position estimate (hippocampal map 'realignment') was correlated with the rat's ability to find the hidden goal. In addition, aged rats were impaired relative to adult rats in both goal-finding accuracy and map realignment. Thus, changes in the effectiveness with which the hippocampal spatial representation is updated on the basis of external cues may contribute to both within-age-group spatial learning variability and age-related spatial learning deficits.

Adaptation, Physiological↗

Molecular indices of neuronal and glial plasticity in the hippocampal formation in a rodent model of age-induced spatial learning impairment.

Spatial learning ability was quantitated in young and aged Long-Evans rats, and molecular markers were assessed in the striatum and hippocampal formation using immunocytochemical, immunoblotting, and in situ hybridization histochemical procedures. The mRNA for beta-amyloid precursor protein (beta APP), most likely the transcript encoding the 695-amino acid form of this protein, was elevated in pyramidal and granule cells in the hippocampus of aged rats exhibiting poorer spatial learning. In immunoblots of hippocampal protein extracts, however, the level of beta APP-like immunoreactivity was depressed in the more impaired subjects. Similarly, the level in hippocampus of the mRNA for manganese-dependent superoxide dismutase (Mn-SOD), a marker of oxidative stress, was positively correlated with the degree of behavioral impairment, but immunoblotting revealed that Mn-SOD protein was depressed in the aged hippocampus compared with young. The mRNAs for the neuronal form of nitric oxide synthase and for the astrocyte marker glial fibrillary acidic protein (GFAP) were elevated in the hippocampus in correlation with the extent of learning impairment. In the striatum, the levels of mRNA and protein for several candidate genes, including GFAP, were elevated in parallel with the learning index, but these were age effects. Several hippocampal proteins were unchanged (GFAP) or depressed (beta APP and Mn-SOD) in level, despite elevations in corresponding mRNAs. In the aged cohort, hippocampal GFAP mRNA, Mn-SOD mRNA, and beta APP emerged as predictors of behavioral impairment, suggesting the involvement of these hippocampal systems in age-related cognitive impairment.

Aging↗

Ethanol impairs behavioral strategy use in naive rats but does not prevent spatial learning in the water maze in pretrained rats.

RATIONALE: Ethanol impairs performance in the water maze in rats. A detailed behavioral analysis is required to fully evaluate the nature of the impairment. OBJECTIVES: A detailed behavioral analysis was carried out to evaluate the effect of ethanol on performance in the water maze task in male hooded rats given 2.0 or 6.0 g/kg ethanol by gavage. Multiple measures of water maze strategies learning and spatial learning were studied. METHODS: Water maze trials were recorded on videotape and digitized for offline analysis. Some rats were naive at the start of spatial training, whereas other rats received water maze strategies pretraining prior to spatial training to familiarize them with the general behavioral strategies required in the task. RESULTS: Naive ethanol-treated rats exhibited both spatial learning and water maze behavioral strategies impairments. There was no evidence of a spatial learning impairment that was independent of an associated behavioral strategies impairment. Further, ethanol impaired the ability of naive rats to swim to a stable visible platform. Pretrained ethanol-treated rats performed significantly better than naive ethanol-treated rats on almost all measures, and were indistinguishable from controls on most measures. CONCLUSIONS: These results suggest that ethanol may impair water maze performance in naive rats by interfering with their ability to acquire and use required water maze behavioral strategies and generate adaptive swim paths. Ethanol does not prevent robust spatial learning in rats that are familiar with required water maze behavioral strategies.

Animals↗

Nitric oxide but not carbon monoxide is involved in spatial learning of mice.

The aim of the present study was to elucidate the role of carbon monoxide (CO) in learning and to compare it with that of nitric oxide (NO). Effects of an inhibitor of heme oxygenase which produces CO, Zn-protoporphyrin IX, on passive avoidance learning and spatial learning in mice were examined using step through, step down and water maze tests. Zn-protoporphyrin IX (10, 20 nmol, i.c.v.) affected neither type of learning. In contrast, N-omega-nitro-L-arginine (40 nmol, i.c.v.), an inhibitor of NO synthase, impaired spatial learning, but not passive avoidance learning. These results suggest that NO but not CO is involved in spatial learning.

Animals↗

Transfer of spatial behavior between different environments: implications for theories of spatial learning and for the role of the hippocampus in spatial learning.

In 3 experiments, rats were required to find a submerged platform located in 1 corner of an arena that had 2 long and 2 short sides; they were then trained to find the platform in a new arena that also had 2 long and 2 short sides but a different overall shape. The platform in the new arena was easier to find if it was in a corner that was geometrically equivalent, rather than the mirror image, of the corner where it had previously been located. The final experiment revealed that hippocampal lesions impaired rats' ability to find the platform in these arenas. The results suggest that rats did not use the overall shape of the arena to locate the platform but relied on more local cues and that the hippocampus plays a role in navigation based on these cues.

Animals↗

The effects of antiepileptic drugs on spatial learning and hippocampal protein kinase C gamma in immature rats.

This study was conducted to determine if alterations in hippocampal protein kinase C (PKC) gamma is one of the cellular mechanisms by which conventional antiepileptic drugs affect learning and memory. Wistar Rats (21-day-old) were divided into five groups: (1) control (no training and drugs); (2) training group (no drugs); (3) phenobarbital (PB) group; (4) carbamazepine (CBZ) group; and (5) valproate (VPA) group. A hippocampus dependent learning task (spatial changing learning) was used in the latter four groups lasting a total of 10 days. Correct responding rate of training group was significantly higher (P < 0.05) than in the PB, CBZ and VPA group. The PKC gamma staining intensity in hippocampal CA1-2 region of training group was significant greater than that of the control and PB group. There was no difference in staining intensities between the CBZ, VPA group or training group. The amount of PKC gamma located in plasma membrane of hippocampal neurons was significantly higher in the training group (P < 0.05) than the control, PB and VPA groups. No differences were found between the training and CBZ group. Lastly, the amount of PKC gamma in cytosol of hippocampus did not significantly differ between any of the five groups. These results indicate that the three antiepileptic drugs used in this study all disturbed the spatial learning of immature rats. Spatial learning was concomitant with activation of PKC gamma in hippocampal neurons. PB and VPA likely adversely affect learning and memory by interfering with PKC gamma activation, whereas CBZ may act by a different mechanism, possibly in the post-translocation process or by a PKC gamma independent pathway.

Animals↗

Caloric restriction and spatial learning in old mice.

Spatial learning in old mice (19 or 24 months old), some of which had been calorically restricted beginning at 14 weeks of age, was compared to that of young mice, in two separate experiments using a Morris water maze. In the first experiment, only old mice reaching criterion performance on a cued learning task were tested in a subsequent spatial task. Thus, all old mice tested for spatial learning had achieved escape latencies equivalent to those of young controls. Despite equivalent swimming speeds, only about half the old mice in each diet group achieved criterion performance in the spatial task. In the second experiment, old and young mice all received the same number of training trials in a cued task and then in a spatial task. Immediately following spatial training, they were given a 60-s probe trial, with no platform in the pool. Both groups of old mice spent significantly less time in the quadrant where the platform had been and made significantly fewer direct crosses over the previous platform location than did the young control group. As in Experiment 1, calorie restriction failed to provide protection against aging-related deficits. However, in both experiments, some individual old mice evidenced performance in spatial learning indistinguishable from that of young controls. Separate comparisons of "age-impaired" and "age-unimpaired" old mice with young controls may facilitate the identification of neurobiological mechanisms underlying age-related cognitive decline.

Aging↗

Inhibition of nitric oxide synthase does not impair spatial learning.

Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved in certain forms of synaptic plasticity and learning. This article reports a series of experiments investigating the effects of N omega-nitro-L-arginine methyl ester (L-NAME) upon various forms of learning and memory in the watermaze. L-NAME (75 mg/kg, i.p., sufficient to bring about > 90% inhibition of NO synthesis in brain) produced an apparent impairment in spatial learning when given to naive rats during acquisition (3 d, six training trials per day). This impairment was dose related, stereoselective, and attenuated by coadministration of L-arginine. A second study showed that L-NAME did not affect the retention of a previously learned spatial task. In addition, in a visual discrimination task, the rate at which criterion levels of performance were reached was unaffected by L-NAME. Thus, inhibition of NO synthase may cause a selective impairment of spatial learning without effect upon retention. However, analysis of the early training trials of the visual discrimination task revealed significantly elevated escape latencies in the L-NAME-treated rats, suggesting that inhibition of NO synthase may have more general effects. As normal rats learn the spatial task very rapidly, the possibility arises that the apparent deficit in learning is due to a disruption of some process other than learning per se. A further series of experiments investigated this possibility. L-NAME was found not to impair the learning of a new platform position in the same spatial environment. Surprisingly, L-NAME also had no effect on spatial learning in a second watermaze located in a novel spatial environment by rats well practiced with all aspects of watermaze training. Finally, L-NAME had no effect on spatial learning in naive rats trained with just one trial per day. Thus, systemic injection of an NO synthase inhibitor impairs behavioral performance in two tasks during their initial acquisition, but the basis of this functional disruption is unlikely to be due to any direct effect upon the mechanisms of spatial learning.

Amino Acid Oxidoreductases↗

Mayo's Older Americans Normative Studies: Age- and IQ-Adjusted Norms for the Auditory Verbal Learning Test and the Visual Spatial Learning Test.

Although normative data sets for standardized neuropsychometric instruments frequently feature adjustments for subject variables, there are reasons to believe that improvements in interpretive accuracy that result from such adjustments are less than optimal. In particular, years of education may be less closely associated with test performances than is overall intellectual functioning. In this last of four reanalyses of results from the Mayo Clinic's Older Americans Normative Studies (MOANS) databases, age-adjusted scores for the Rey Auditory Verbal Learning Test and the Visual Spatial Learning Test were found to be more strongly related to Mayo age-adjusted WAIS-R Full Scale IQ scores (rs=.150 to .395) than to education (rs=.060 to .236) for healthy older examinees between 56 and 99 years of age. Although AVLT-FSIQ correlations were greatest at moderate levels of intelligence, VSLT-FSIQ correlations consistently increased in strength as intelligence increased (cf. Dodrill, 19971999). Based on these results, we present tables of age- and IQ-adjusted percentile equivalents of Mayo age-adjusted AVLT index scores and MOANS age-adjusted AVLT and VSLT scaled scores for ten age ranges and either seven (AVLT) or five (VSLT) IQ ranges.

Acoustic Stimulation↗

Methamphetamine exposure from postnatal day 11 to 20 causes impairments in both behavioral strategies and spatial learning in adult rats.

Spatial learning and memory deficits in a water maze have been observed in adult animals exposed to a regimen of 4 daily doses of d-methamphetamine (MA) at 2 h intervals from postnatal day 11 to 20. An interpretational issue for these long-term effects of MA is whether they are truly spatial deficits or are secondary to alterations in sensorimotor systems. In this experiment, we evaluated the effects of a pretraining procedure shown to minimize the influence of drug-induced sensorimotor deficits. Animals within a litter were treated with MA or saline. Animals were either pretrained for nonspatial task requirements in the water maze (i.e., swimming and platform climbing) or were nai;ve to the task. Animals that received the pretraining did better than the nai;ve animals. The nai;ve MA animals performed worse than the nai;ve control animals as previously observed. By contrast, no difference in search time was noted between pretrained MA- and SAL-treated animals during the acquisition phase of testing. When the platform was relocated in a novel position, spatial learning was impaired for MA animals, regardless of pretraining. No increase in the number of platform nonrecognition events (swimovers, deflections, or jump-offs) occurred among pretrained or nai;ve groups compared to controls. These data suggest that sensorimotor deficits do not account for the spatial learning and memory deficits in animals exposed neonatally to MA.

Animals↗

The effects of central catecholamine depletions on spatial learning in rats.

The role of forebrain catecholamine systems in spatial learning was assessed using a recently described place navigation task. Rats were required to learn the spatial location of a platform hidden 1 cm below the surface in order to escape from a large pool filled with opaque water. Circumscribed destruction of dopamine or noradrenaline neurones was achieved with bilateral stereotaxic injections of 6-hydroxydopamine. Rats with neostriatal dopamine depletions showed regulatory impairments, mild akinesia and increased latencies to escape during training on both the spatial task and on a non-spatial control task. However their normal transfer test performance indicated that their deficit was not due to impaired spatial learning. Similarly, spatial learning and transfer test performance were unimpaired by mesocorticolimbic dopamine depletions or by extensive noradrenaline loss in cortex and hippocampus following dorsal noradrenergic bundle lesions. These findings suggest that considerable spatial learning can occur in the absence of each of the major telencephalic catecholamine systems.

Afferent Pathways↗