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PubMed1989

Deficient programming in spatial learning after frontal lobe damage.

Patients with anterior or posterior brain damage and control subjects performed a spatial sequence learning task in which the score obtained depended on the subject's ability to set sub-goals appropriate for his learning capacity. The anterior group obtained lower scores and more frequently set inadequate sub-goals than the posterior group. No anterior vs posterior difference was found on a similar learning task in which another sequence was learnt by predetermined sub-goals. The result supported the hypothesis that frontal lobe lesions disturb programming or goal-based search for action structure on spatial learning.

Adult↗
PubMedDate not supplied

Glucose treatment attenuates spatial learning and memory deficits of aged rats on tests of hippocampal function.

Groups of old and young rats were administered three tests of spatial learning and memory that are known to be sensitive to hippocampal dysfunction: the radial arm maze (RAM), spatial non-matching-to-sample (SNMTS), and a spatial vs. local cue-preference task. Old rats performed worse than young rats on the RAM and SNMTS tasks; on the cue-preference task, young rats were biased to use spatial cues, whereas old rats exhibited strong preferences for distinct, local cues. Peripheral injections of glucose (100 mg/kg) improved performance by old rats on the RAM and SNMTS, which correlated with measures of glucose metabolism. Glucose treatment did not affect old rats performance on the cue-preference task. There was evidence that glucose-treatment improved performance of young rats in the RAM test, but not the other tests. The results extend the range of tasks on which glucose-induced cognitive enhancement has been demonstrated in aged rats, and provides further evidence that memory loss resulting from hippocampal dysfunction is especially amenable to glucose treatment.

Aging↗
PubMed1999

Early postnatal treatment with ACTH4-9 analog ORG 2766 improves adult spatial learning but does not affect behavioural stress reactivity.

Studies on adult animals and humans have shown that the ACTH4-9 analog ORG 2766 influences cognitive performance and possibly has neurotrophic effects. For this reason we studied the effect of ORG 2766 applied in early postnatal life when brain structures and neuronal pathways are still developing. Our aim was to see whether such treatment during development would result in permanent changes in adult behavioural performance. Pups received subcutaneous injections of 1 microg/g bodyweight ACTH4-9 analog ORG 2766 on day 1, 3 and 5 after birth. Control animals in the same nest received saline injections. When the animals had reached an adult age of 3 months they were subjected to a series of tests to measure their behavioural performance. In the first experiment, behavioural stress responses and anxiety were measured by subjecting the rats to the following tests: open field, defensive burying, elevated plus maze, and conditioned fear test. In a second experiment, adult cognitive function was measured in the Morris water-maze, a hippocampus-related spatial learning test, and in the active avoidance test, a more amygdala-related nonspatial test. The results showed that animals treated with ORG 2766 during early postnatal life learned faster in the spatial Morris water-maze. The treatment had a positive effect on performance during the acquisition phase of the learning task, while memory retrieval was not affected. Learning in the nonspatial active avoidance task did not change due to the postnatal ACTH4-9 treatment. In addition, there were no differences in the open field test, the defensive burying test, elevated plus maze and the conditioned fear test. The latter supports the conclusion that the differences in water-maze performance was due to a difference in learning speed, rather than a difference in anxiety or behavioural stress reactivity. Analysis of [3H]CORT binding capacity measured after the learning tests revealed no differences in the hippocampal MR and GR concentration between non-treated and treated animals.

Adrenocorticotropic Hormone↗
PubMed1993

Phencyclidine disrupts long- but not short-term memory within a spatial learning task.

In the first experiment rats with 1, 2, 3 or 4 mg/kg phencyclidine (PCP), or saline injections were tested for acquisition or retention of a cheese board spatial task (dry land version of a water maze). Results indicate that relative to controls or rats with injections of 1 and 2 mg/kg PCP, rats with 3 or 4 mg/kg PCP injections were impaired in acquisition and retention of the task as measured by increased distances traveled to find the correct food location. This impairment was primarily observed in between days but not within days performance. In the second experiment rats with 4 mg/kg PCP or saline injections were tested for memory performance of a delayed spatial matching-to-sample task. Results indicate that relative to controls rats with 4 mg/kg PCP injections were not impaired at either 1-5 or 30 s delays. It is suggested that PCP through its blocking action of the NMDA receptor mediates long- but not short-term memory for spatial location information as well as the ability to retrieve previously learned spatial location information.

Analysis of Variance↗
PubMed2004

Effect of lead exposure on spatial learning and running speed in the short-tailed opossum, Monodelphis domestica (Didelphidae).

Studies were conducted to assess the spatial learning ability in adult males of the short-tailed opossum, Monodelphis domestica using a T-maze, complex maze and elevated radial 8-arm maze. This is the first study of maze learning in opossums. In the T-maze, the performance of these animals improved over an 8-day training period. Eighty percent of the subjects initially trained to turn to the right for food reinforcement reached criterion (80% correct responses) by day 3 and all reached criterion by day 4. Reversal training (subjects then trained to turn to the left) was more difficult and required 8 days for all subjects to reach criterion. In the complex maze, 89% of the animals achieved the criterion level of performance (3 consecutive trials with 5 or fewer errors) on the eighth day of training and all reached criterion by day 10. The relative importance of intramaze vs. extramaze cues in directing choice behavior was investigated in the radial arm maze. A discrimination procedure was used which selectively rewarded subjects for following only one set of cues. Animals in the intramaze group obtained a food pellet from a cup at the end of each arm. In the extramaze group, the food cups were placed on a small platform just beyond the end of each arm. All subjects were initially trained to visit each arm with the maze in a fixed position (controls) and did so within 15 test sessions. Following these initial trials, the maze was rotated to a different position after each choice. For subjects in the intramaze group, the food moved in conjunction with the rotation of the arms thereby increasing the relevance of intramaze cues. In the extramaze group, extramaze cues became more important because the food remained on the platforms in the same position in the room. Animals in the extramaze group performed significantly better than chance whereas the intramaze subjects did not. This indicates that intramaze cues are not as important as extramaze cues for accurate choice behavior in this marsupial. In addition, animals injected with tetraethyllead showed a significant impairment in running speed and T-maze learning ability as compared to saline-injected controls.

Animals↗
PubMed1996

Spatial learning alters hippocampal calcium/calmodulin-dependent protein kinase II activity in rats.

This study investigated the role of hippocampal CaM-kinase II (calcium/calmodulin-dependent protein kinase II) in spatial learning. In Experiment I, three groups of rats received 1, 2 or 5 days of training on a spatial task in the Morris water maze with a hidden platform, while a control group was trained on a nonspatial task with a visible platform. The acquisition rate in the spatial task was slower than that in the nonspatial task. However, rats receiving 5 days of spatial training had the highest Ca(2+)-independent activity of CaM-kinase II compared with the controls receiving nonspatial training and rats having 1 or 2 days of spatial training. Furthermore, the level of hippocampal Ca2+-independent CaM-kinase II activity was correlated with the final performance on the spatial task. In Experiment II, rats received intra-hippocampal injections of a specific CaM-kinase II inhibitor-KN-62-before each training session. In comparison with the vehicle-injected controls, pretraining injection of KN-62 retarded acquisition in the spatial task but had no effect on the nonspatial task. These results, taken together, indicated that the activation of CaM-kinase II in the hippocampus is not only correlated to the degree of spatial training on the Morris water maze, but may also underlie the neural mechanism subserving spatial memory.

Animals↗
PubMed2001

Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning.

Rats solving a simple spatial discrimination task in a plus maze initially employ a place-learning strategy, then switch to a motor response strategy. The hippocampus is required for the use of a place-learning strategy in this task. Rats with 192 IgG-saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB), that selectively removed cholinergic neurons projecting to the hippocampus, were significantly facilitated in acquisition of the spatial discrimination, and switched from place to response strategies just as control rats did. Rats with ibotenic acid lesions of the MS/VDB, that produced cell loss in the MS/VDB but little damage to cholinergic neurons, were significantly impaired in acquiring the spatial discrimination and did not reliably employ either a place or response strategy at any point in training. This suggests that the MS/VDB modulates hippocampal involvement in place learning, but that cholinergic MS/VDB neurons are neither necessary nor sufficient for using a place strategy to solve a spatial discrimination.

Acetylcholine↗
PubMed2003

Effects of positive GABA(A) modulators on a multiple-component, repeated-acquisition test of spatial learning.

The purpose of this study was to determine the effects of the benzodiazepines, midazolam and chlordiazepoxide, and the barbiturate, pentobarbital, on spatial learning, in a within-subject, repeated-acquisition and performance procedure adapted to the Morris Swim Task. In the presence of one stimulus arrangement, rats learned to swim to a hidden escape platform that was always in the same location in a swimming pool (performance component). In the presence of a second stimulus arrangement, the platform moved to a different place in the pool for each daily session (acquisition component). All subjects completed six training trials in both components during each daily training session, alternating between the two components within each session. Relatively direct paths to the platform and short escape latencies in the performance component, and steep within-session learning curves in the acquisition component, demonstrated that behavior under each component was controlled by the discriminative stimuli. All three GABA(A) modulators increased swim distances, escape latencies, and slowed swim speed in a dose-dependent manner. Midazolam and chlordiazepoxide, but not pentobarbital, produced selective impairments of swim distances and escape latencies in the acquisition component. Benzodiazepines disrupted acquisition at doses that did not disrupt steady-state performance. Pentobarbital impaired acquisition only at doses that also disrupted behavior during the performance component and reduced swimming speeds.

Animals↗
PubMed2000

Spatial learning affects immature granule cell survival in adult rat dentate gyrus.

Neurogenesis occurs throughout life in mammalian dentate gyrus. The effect of learning on newborn cell survival was studied in rat. Rats were trained on a hippocampus-dependent spatial learning task by using Morris water maze. Neurogenesis was evaluated by 5-bromo-2'deoxyuridine administered before learning. Several newborn cells expressed the immature neuron marker TOAD-64. The main findings were as follows: (1) the survival of newborn cells was enhanced by learning at early stage of differentiation; (2) the newborn cells saved by learning were mainly located in the rostral part of external blade of granule cell layer and (3) there was a correlation between the actual individual learning and newborn cell survival.

Age Factors↗
PubMed1996

Adverse effects of dextromethorphan on the spatial learning of rats in the Morris water maze.

The effects of the non-competitive NMDA receptor antagonist dextromethorphan on spatial learning were assessed using the Morris water maze. Dextromethorphan was administered to 4 groups of rats in 10, 20, 30, and 40 mg/kg doses. An additional group of rats was administered saline to serve as a vehicle control group. Dextromethorphan impaired learning dose dependently in the initial training phase of the experiment. During the probe trial, dose-dependent performance deficits were noted in the first 15 s of the trial only. Search strategy differences between the lowest and highest dose groups were also observed during the probe trial. During the reversal training phase, when the platform was moved to a new location, the dose-dependent impairment was seen again, but the 40 mg/kg group perseverated to the former location longer than the other groups. A cued control trial indicated that in addition to the learning impairment produced, the highest dose of dextromethorphan may also impair sensory-motor coordination.

Animals↗
PubMed1997

A rotating holeboard procedure for testing drug effects on spatial learning and memory in mice.

A procedure is described herein for evaluating drug effects on acquisition and retention of a spatial learning task in mice. The rotating holeboard apparatus is a rectangular open field containing four open holes arranged in either a four-corner or a row configuration. A mouse is trained to poke its head into a hole and retrieve a food reward from a 'baited' hole which contains a reward on every trial. A massed trials protocol is used where mice are required to learn a reference (trial-independent) memory task in a single session. A retention test is administered 24 h after acquisition. Prominent distal cues are present in the testing room and reliance on proximal visual, olfactory, or tactile cues for locating the baited hole is precluded by rotating the maze on each trial.

Animals↗
PubMed2003

Morphological changes in hippocampal dentate gyrus synapses following spatial learning in rats are transient.

The hippocampus is believed to play a crucial role in the formation of memory for spatial tasks. In the present study quantitative electron microscopy was used to investigate morphological changes in the hippocampal dentate gyrus of 3-month-old male rats at 3, 9 and 24 h after training to find a hidden platform in a Morris water maze. Average escape latency (time taken to reach the platform) in all trained groups decreased progressively with increased training but data from a probe trial (quadrant analysis test) at the end of training indicated that only animals in the 9- and 24-h groups, not the 3-h group, displayed significant retention of platform location. Unbiased stereological methods were used to estimate synapse and neuronal density at each time point after training. The majority of synapses had unperforated postsynaptic densities, were localized on small dendritic spines and were classed as axo-spinous. In comparison to age-matched untrained rats, significant but transient increases were observed in axo-spinous synapse density and synapse-to-neuron ratio 9 h after the start of training, but not at earlier (3 h) or later (24 h) times. These changes at 9 h post-training were accompanied by transient decreases in both mean synaptic height and area of postsynaptic density. No such changes were observed in an exercise-matched control group of rats, indicating that the transient synaptic changes in the dentate gyrus are most likely to be specifically related to processes involved in memory formation for the spatial learning task.

Animals↗
PubMed2003

Complete sparing of spatial learning following posterior and posterior plus anterior cingulate cortex lesions at 10 days of age in the rat.

Neonatal posterior cingulate cortex lesions spare the spatial deficits that characterize adult lesions. The present experiments examined the possibility that the anterior cingulate cortex mediates the spared spatial behavior. Rats were given bilateral lesions of the posterior cingulate cortex or anterior plus posterior cingulate cortex on postnatal days 4 (P4), 10 (P10), or in adulthood (P120). All groups were tested for spatial learning on the Morris place task in adulthood. Adult animals were impaired on place learning relative to controls whereas place learning was spared in all the neonatal groups and sparing was complete in the group receiving day 10 lesions. The results are discussed in relation to neural mechanisms, including fiber rerouting, synaptic changes and generation of new neurons, that may mediate spared spatial following neonatal posterior cingulate cortex lesions. Also discussed is evidence indicating that the neonatal brain, especially the day 10, has a special ability to compensate for injury.

Animals↗
PubMed1997

GM1 ganglioside improves spatial learning and memory of aged rats.

GM1 ganglioside, 30 mg/kg, i.p., was administered to cognitively impaired aged rats for 30 days, and spatial learning and memory evaluated in a Morris water maze paradigm. During treatment with GM1, aged animals improved both the acquisition and retention of place navigation, as reflected by reduced escape latencies and swim distances to a hidden platform, and persistently performed better than the aged control animals. Furthermore, the GM1-treated animals showed improved spatial acuity in a spatial probe test when the hidden platform was removed. The improved performance in place navigation was not lost if GM1 treatment was discontinued and the animals tested up to 15 days later. GM1 treatment had no effect on the performance of young rats in the water maze. These results indicate that memory deficits associated with aging can be attenuated by treatment with GM1 ganglioside.

Aging↗
PubMed1999

WAY 100635, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by blockade of hippocampal NMDA receptors.

We studied the effect of WAY 100635, a 5-HT1A receptor antagonist, on the impairment of spatial learning caused by intrahippocampal injection of 3-((R)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive NMDA receptor antagonist, in a two-platform spatial discrimination task. CPP, 3 and 10 ng/microl, administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, dose-dependently reduced choice accuracy in the two-platform spatial discrimination task with little or no effect on choice latency and errors of omission. A volume of 10 ng/microl intrahippocampal CPP did not affect choice accuracy or latency of a non-spatial visual discrimination task. Subcutaneous doses of 0.3 and 1 mg/kg WAY 100635 did not modify the choice accuracy, but prevented the impairment caused by 10 ng/microl intrahippocampal CPP. A dose of 20 ng/microl WAY 100635 into the dorsal hippocampus prevented the deficit caused by 10 ng/microl CPP administered in the same region. The results suggest that blockade of 5-HT1A receptors can compensate the loss of NMDA-mediated excitatory input to pyramidal cells in the hippocampus. These findings may have clinical relevance for the symptomatic treatment of memory disorders associated with reduced glutamate transmission mediated by NMDA receptors.

Animals↗
PubMed2004

Double dissociation of social and environmental stimulation on spatial learning and reversal learning in rats.

Environmental enrichment induces structural and biochemical changes in the brains of mammals that correlate with improved learning and memory. Research in rats suggests that social compared to inanimate stimulation might affect behavior differently, by acting upon dissociable neural substrates. Here we tested this hypothesis at the behavioral level by examining whether social and inanimate stimulation affect spatial memory formation and non-spatial discrimination reversal learning selectively. Spatial memory formation is known to depend on hippocampal-neocortical pathways, whereas reversal learning depends primarily on prefrontal cortico-striatal pathways. Male Lister hooded rats were housed singly or in groups of three in either small barren or large enriched cages, from weaning onwards. After 10 weeks of differential housing, spatial learning and memory were examined in the Morris water maze, followed by a series of tactile and odour discriminations, including discrimination reversal, in a two-choice discrimination task. Regardless of inanimate stimulation, social deprivation affected neither the acquisition of simple or complex discriminations, nor spatial memory formation, but was associated with impaired reversal learning in the two-choice discrimination task. By contrast, inanimate deprivation, regardless of social stimulation, affected neither acquisition nor reversal of two-choice discriminations, but selectively delayed the acquisition of spatial memory in the Morris water maze. This is the first demonstration of a double dissociation of early social and inanimate stimulation on two distinct behavioural functions that are mediated by dissociable underlying neural pathways. These findings strengthen the view that social and inanimate stimulation act, at least in part, upon dissociable neural substrates.

Animals↗
PubMed1993

Lack of strain differences in spatial learning among seizure-prone and seizure-resistant mice.

Learning rates were examined in the following inbred mice strains: DBA/2, C3H/He, C57B1/6J, E1, and ddY. DBA/2 mice become susceptible to audiogenic seizures after 2-3 weeks of age and E1 mice have generalized seizures in response to handling after 3 months of age, but the remaining three strains do not develop seizures. In this study, mice from all five strains underwent 32 training trials in a Morris water maze at 7-9 weeks of age. The seizure-prone DBA/2 and E1 mice, along with the nonepileptic ddY and C57B1/6J mice, exhibited learning at similar rates, but the nonepileptic C3H/He mice were unable to learn the water maze task, probably due to visual difficulties. In the C57B1/6J strain only, female mice learned the task significantly faster than males. There was no difference in the learning rate between the E1 strain and its parent ddY strain, or any correlation between spatial learning ability and kindling rates in these strains.

Animals↗