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Results for “Spatial Learning”

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At least 181 records · Page 10Linked to original sources

PubMed1999

Ibotenate lesions of the hippocampus impair spatial learning but not contextual fear conditioning in mice.

Recently, gene targeting and other mouse transgenic techniques have been used to study the cellular mechanisms underlying learning and memory mechanisms in the hippocampus. A key assumption of many of these studies is that lesions of the hippocampus have a similar impact on learning and memory in mice and in rats. Here, we used axon-sparing ibotenate lesions to determine whether damage to the hippocampus disrupts spatial learning and contextual conditioning in mice, as it is known to do in rats. Our results demonstrated that hippocampal lesions impair performance in the hidden-platform version of the water maze under a variety of experimental conditions. Neither keeping the start site constant, nor prior training with the visible-platform task fully rescued the spatial learning deficits of the lesioned mice. As previously shown in rats, the lesions left the performance of the mice intact in the visible-platform version of the water maze, indicating that they do not affect all types of learning, and that disruptions of sensory processing or motivation probably did not account for their deficits in the hidden-platform task. In contrast, the very same lesions did not affect either cued or contextual fear conditioning. These results confirm the involvement of the hippocampus in spatial learning in mice, and they also demonstrate that hippocampal-lesioned mice can show contextual fear conditioning. Thus, the behavioral findings presented here are crucial for the interpretation of transgenic experiments with the widely used water maze and fear-conditioning paradigms.

Animals↗

PubMed1996

Intact spatial learning following lesions of basal forebrain cholinergic neurons.

The role of the basal forebrain cholinergic system in learning and memory has held considerable interest since the discovery of cholinergic neurodegeneration in the basal forebrain in Alzheimer's disease. Contrary to expectation, selective removal of basal forebrain cholinergic neurons projecting to either hippocampus or neocortex fails to impair learning in a spatial task widely used to study hippocampal/cortical function. If cholinergic neurons contribute to learning and memory by integrated regulation of hippocampal and cortical processing, combined removal of hippocampal and cortical cholinergic projections might be necessary to produce impairment. However, this combined lesion failed to impair spatial learning. These data argue against the view that basal forebrain cholinergic deficiency plays a prominent role in disorders of learning and memory.

Acetylcholine↗

PubMed1995

The effects of d-cycloserine, a partial agonist at the glycine binding site, on spatial learning and working memory in scopolamine-treated rats.

The present study investigated the effect of d-cycloserine, a partial agonist at the glycine binding site on NMDA receptor complex, on the performance of scopolamine-treated adult rats in a water maze task assessing spatial learning and in a delayed non-matching to position task assessing working memory in a spatial context. In the spatial learning task, scopolamine (0.4 mg/kg, i.p.) impaired acquisition (increased escape latency and distance) and increased swimming speed of rats. D-cycloserine (1.0 mg/kg, i.p.) reversed the deficits in acquisition performance but not the increases in behavioral activity. In the working memory task, scopolamine (0.2 mg/kg, i.p.) produced deficits on nonmnemonic rather than on mnemonic performance factors; scopolamine delay-independently decreased the percent correct responses and reduced behavioral activity of rats. D-cycloserine (1.0, 3.0 and 10 mg/kg, i.p.) did not reverse these performance deficits. When administered alone, the moderate to higher doses of d-cycloserine had no effects on working memory but the lower dose produced slight deficits in mnemonic performance factors; the 1.0 mg/kg dose delay-dependently decreased the percent correct responses without affecting behavioral activity of rats. In the water maze task, d-cycloserine had no effects on acquisition performance or behavioral activity of rats. These results suggest that acute, systemic administration of d-cycloserine does not improve spatial learning or working memory. However, at appropriate doses this agent may be efficacious in disease states of central cholinergic hypofunction since 1.0 mg/kg d-cycloserine was able to reverse the scopolamine-induced deficits in acquisition.

Animals↗

PubMed2002

Does head-only exposure to GSM-900 electromagnetic fields affect the performance of rats in spatial learning tasks?

The rapid expansion of mobile communication has generated intense interest, but has also fuelled ongoing concerns. In both humans and animals, radiofrequency radiations are suspected to affect cognitive functions. More specifically, several studies performed in rodents have suggested that spatial learning can be impaired by electromagnetic field exposure. However, none of these previous studies have simulated the common conditions of GSM mobile phones use. This study is the first using a head-only exposure system emitting a 900-MHz GSM electromagnetic field (pulsed at 217 Hz). The two behavioural tasks that were evaluated here have been used previously to demonstrate performance deficits in spatial learning after electromagnetic field exposure: a classical radial maze elimination task and a spatial navigation task in an open-field arena (dry-land version of the Morris water maze). The performances of rats exposed for 45 min to a 900-MHz electromagnetic field (1 and 3.5 W/kg) were compared to those of sham-exposed and cage-control rats. There were no differences among exposed, sham, and cage-control rats in the two spatial learning tasks. The discussion focuses on the potential reasons that led previous studies to conclude that learning deficits do occur after electromagnetic field exposure.

Animals↗

PubMed1993

Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat.

The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.

Administration, Inhalation↗

PubMed2002

Differential effect of corticosterone on spatial learning abilities in apolipoprotein E knockout and C57BL/6J mice.

Previously, we found that repeated exposure to predator stress corrected the deficit in spatial learning of apolipoprotein E-knockout (apoE0/0) mice, but impaired cognitive performance of wild-type mice. Here we show that elevated corticosterone concentrations, accomplished by subcutaneously implanted pellets, results in similar genotype-related effects on water maze learning: while apoE0/0 mice improved their spatial learning abilities, wild-type mice (C57/Bl6J) became impaired. These results suggest that corticosterone mediates the lasting effects of environmental challenges on apoE-genotype related cognitive performance.

Animals↗

PubMedDate not supplied

A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning.

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.

Animals↗

PubMed1996

Landmark stability: further studies pointing to a role in spatial learning.

Two experiments were conducted to investigate the possible role of landmark stability in spatial learning. Rats were trained to search in a large arena for food hidden at a consistent distance and direction from either a single radially symmetric landmark or an array of two landmarks. We varied the relative degree to which the landmark array and/or the cues of the training context predicted the location of food, without varying the conditional probability of food being available given either cue. Experiment 1 used vestibular disorientation to ensure control of search location by experimenter-controlled cues. The results showed that making either a single landmark or a cluster of two adjacent landmarks the sole spatial predictor of reward location reduced the accuracy of search compared to a condition where both the landmark array and context cues were reliable spatial predictors. Varying global landmark stability had no effect when training was conducted using an array of two landmarks located some distance from each other. Context cues, when tested alone, triggered very little searching in appropriate locations, and the absolute magnitude of control over search was insufficient to account for the superiority of stable landmarks. The better learning with a stable landmark, and the dependence of this effect on the geometrical arrangement of landmarks, points to the conditions of spatial learning involving additional principles to those of simple associative conditioning. Experiment 2 examined landmark stability using a single landmark and fixed directional cues in the absence of vestibular disorientation. This also revealed a relative advantage of landmark stability, but animals with a landmark that moved from trial to trial did show some evidence of learning. Context cues when tested alone had minimal influence. Parametric manipulation of landmark stability offers a novel way of influencing spatial learning and thus understanding better the process through which egocentric representations of perceived space are transformed into allocentric representations of the real world.

Animals↗

PubMed2005

The slow afterhyperpolarization in hippocampal CA1 neurons covaries with spatial learning ability in aged Fisher 344 rats.

Rodents commonly exhibit age-related impairments in spatial learning tasks, deficits widely thought to reflect cellular or synaptic dysfunction in the hippocampus. Using whole-cell recordings, we examined the afterhyperpolarization (AHP) in CA1 pyramidal cells in hippocampal slices from young (4-6 months of age) and aged (24-26 months of age) Fisher 344 male rats that had been behaviorally characterized in the Morris water maze. The slow AHP (sAHP) recorded from learning-impaired aged rats (AI) was significantly larger than that seen in either age-matched unimpaired rats or young controls. Among aged rats, sAHP amplitude was inversely correlated with both acquisition and probe performance in the water maze. Action potential parameters among the three groups were similar, except for spike accommodation, which was more pronounced in the AI group. Intracellular application of the cAMP analog 8-CPT-cAMP suppressed the sAHP but failed to reveal any age- or performance-related differences in the medium AHP. 8-CPT-cAMP abolished the age-related difference in spike accommodation, whereas instantaneous firing frequency was unchanged. Calcium spikes were of similar amplitude in all three groups but were broader and had significantly larger tails in aged rats; these age-related changes could be mimicked in young neurons after exposure to BayK8644. The calcium spike among aged rats correlated with task acquisition in the maze but, unlike the sAHP, failed to correlate with probe performance. This is the first demonstration that sAHP amplitude covaries with spatial learning ability in aged rats, implying that CA1 excitability strongly influences certain aspects of cognitive function. Our findings also indicate that multiple processes, in addition to elevated calcium influx, conspire to induce cognitive decline during aging.

Action Potentials↗

PubMed2001

Deterioration of spatial learning performances in lipopolysaccharide-treated mice.

It is well demonstrated that acute or chronic stress leads to reduction of learning ability. Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, induces profound physiological and behavioral changes, including fever, decrease in food motivation, and decrease in social behavior. These changes might be interpreted as an acute stress reaction to the LPS. In the present study, therefore, we investigated the effects of LPS (400-800 microg/kg, i.p.) on spatial learning performances using C57BL/6J male mice. In the Morris water-maze task, spatial learning performances were examined in six trials of training for two consecutive days. LPS-treated mice took a longer time to reach the hidden platform than control mice (F(1,60)=4.80801, P<0.05 at 600 microg/kg). In addition, injection of LPS decreased the percent of correct choices in the Y-maze test (P<0.05 at 800 microg/kg). LPS, however, did not alter the body weight, grip tone, motor activity or swimming speed. Taken together, these results indicate that LPS treatment specifically impaired spatial learning performances.

Animals↗

PubMed2002

A hippocampal NR2B deficit can mimic age-related changes in long-term potentiation and spatial learning in the Fischer 344 rat.

Aged rats are known to have deficits in spatial learning behavior in the Morris water maze. We have found that aged rats also have deficits in NR2B protein expression and that the protein expression deficit is correlated with their performance in the Morris water maze. To test whether this NR2B deficit was sufficient to account for the behavioral deficit, we used antisense oligonucleotides to specifically knock down NR2B subunit expression in the hippocampus of young rats. NR2B antisense treatment diminished NMDA receptor responses, abolished NMDA-dependent long-term potentiation (LTP), and impaired spatial learning. These data demonstrate the important role of NR2B in LTP and learning and memory and suggest a role for reduced NR2B expression in age-related cognitive decline.

Action Potentials↗

PubMed1992

The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro.

This series of experiments investigated whether the NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) could induce impairments of spatial learning across a dose range comparable to its impairment of hippocampal long-term potentiation (LTP) in vivo. Estimations of the extracellular concentration of D-AP5 in hippocampus using microdialysis were also made to compare whether these impairments occur at concentrations similar to those required to impair LTP in the in vitro hippocampal slice. Rats were chronically infused with D-AP5 into the lateral ventricle at a range of concentrations (0-50 mM) via osmotic minipumps. They were first trained to find and escape onto a hidden platform in an open-field water maze task. After the behavioral learning, they were anesthetized with urethane and an attempt was made to evoke and monitor hippocampal LTP. Extracellular samples of D-AP5 in hippocampus were then taken using microdialysis, and finally, the animals were killed and tissue samples dissected. The microdialysis and tissue samples were analyzed for D-AP5 content using HPLC with fluorescence detection. The results established, first, that D-AP5 impairs spatial learning in a linear dose-dependent manner, highly correlated with its corresponding impairment of hippocampal LTP in vivo. No concentration of D-AP5 was observed to block LTP without affecting learning. Second, the microdialysis estimates indicated that, subject to certain assumptions, D-AP5 causes these impairments at extracellular concentrations comparable to those that impair LTP in vitro. Third, comparison of the whole tissue and microdialysis samples revealed a concentration ratio of approximately 30:1, indicating that 97% of the intracerebral D-AP5 is inaccessible to the dialysis probes. Infusion of 20 mM EGTA was found to cause a sevenfold increase in D-AP5 in the dialysis perfusates, suggesting that at least part of the inaccessible D-AP5 is trapped by a calcium-dependent mechanism. Two further behavioral control studies indicated that the D-AP5-induced impairment of spatial learning is unlikely to be secondary to a drug-induced motor disturbance, and that the performance of the D-AP5 group whose concentration was just sufficient to block hippocampal LTP completely was statistically indistinguishable from that of a group of rats with bilateral hippocampal lesions induced by ibotenic acid. Taken together, these findings offer support for the hypothesis that activation of NMDA receptors is necessary for certain kinds of learning.

2-Amino-5-phosphonovalerate↗

PubMed1992

Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice.

Although long-term potentiation (LTP) has been studied as the mechanism for hippocampus-dependent learning and memory, evidence for this hypothesis is still incomplete. The mice with a mutation in the alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII), a synaptic protein enriched in the hippocampus, are appropriate for addressing this issue because the hippocampus of these mice is deficient in LTP but maintains intact postsynaptic mechanisms. These mutant mice exhibit specific learning impairments, an indication that alpha-CaMKII has a prominent role in spatial learning, but that it is not essential for some types of non-spatial learning. The data considerably strengthen the contention that the synaptic changes exhibited in LTP are the basis for spatial memory.

Animals↗

PubMed2002

Social isolation stress during the third week of life has age-dependent effects on spatial learning in rats.

Despite extensive research on the relationship between acute stress and hippocampal function in adults, little is known about the short- and long-term effects of prolonged juvenile stress on learning, memory, and other hippocampal functions. This experiment investigated whether spatial learning would be altered in juvenile and adult rats previously exposed to a chronic stressor: 6 h of social isolation (SI) daily at 15-21 days of age. SI was found to increase circulating plasma levels of corticosterone (CORT) and allopregnanolone (3-alpha,5-alpha-pregnan-20-one; 3,5-THP) at 1 h after separation on the fourth day, indicating that the isolation was an effective stressor. When tested as juveniles (post-natal (PN) 22-24), spatial learning was impaired on the Morris water maze in the previously isolated subjects compared to non-isolated controls. However, when tested as adults (PN 92-94), subjects previously exposed to SI during the third week of life demonstrated more rapid learning of the task than controls. These results are discussed in light of research on the effects of CORT on the developing hippocampus.

Aging↗

PubMed2001

Influence of a beacon on spatial learning based on the shape of the test environment.

In 5 experiments rats were required to escape from a triangular shaped pool by swimming to a submerged platform. The principal group of interest in each experiment received training with a beacon attached to the platform. The purpose of the experiments was to assess if the beacon overshadowed (Experiments 1-4) or blocked (Experiment 5) learning about the position of the platform with reference to the shape of the pool. The platform was located in the center of the pool for the first 2 experiments and in a corner for the remaining experiments. Although there was an overshadowing effect in Experiment 1, the remaining experiments failed to reveal any disruptive influence of the beacon on learning based on the shape of the pool. Moreover, in Experiments 3-5 there was an indication that the beacon facilitated such learning. The results suggest that spatial learning based on the shape of a test environment may not take place in the same way as that based on more discrete landmarks.

Animals↗

PubMed2006

Effects of dorsal and ventral vertical lobe electrolytic lesions on spatial learning and locomotor activity in Sepia officinalis.

This study aims to analyze the effects of electrolytic lesion, restricted to either the ventral or the dorsal parts of the vertical lobe (VL), on the behavior of cuttlefish (Sepia officinalis). Two behavioral tests were performed on sham-operated and lesioned cuttlefish: assessment of locomotor activity in an open field and determination of spatial learning abilities in a T maze. The results showed that ventral lesions of the VL led to marked impairment in the acquisition of spatial learning, whereas dorsal lesions of the VL increased locomotor activity in the open field and impaired long-term retention of spatial learning. This study establishes for the first time the existence of distinct functions in the ventral and the dorsal parts of the VL in cephalopods.

Animals↗

PubMed2003

Repeated administration of phencyclidine, amphetamine and MK-801 selectively impairs spatial learning in mice: a possible model of psychotomimetic drug-induced cognitive deficits.

Cognitive deficits are a key feature of schizophrenia. N-Methyl-D-aspartate (NMDA) receptor antagonists and amphetamine are known to induce psychotic behaviors and cognitive deficits in animals and humans, often affecting visuo-spatial abilities. Phencyclidine (PCP), MK-801 and amphetamine (AMPH) have been used in pharmacological animal models of schizophrenia, but none of these models has focused so far on spatial learning after repeated administration of the drugs. The objective of this study was to test whether repeated administration of PCP, AMPH or MK-801 influenced the performance of mice in a non-associative spatial learning test. CD-1 male mice were given i.p. daily injections of either saline, PCP (5.0, 10.0 mg/kg), AMPH (2.5, 5 mg/kg) or MK-801 (0.3, 0.6 mg/kg), for 5 days. On day 6 all mice were tested in an open field containing five different objects. After three sessions of habituation, each animal's reactivity to object displacement and object substitution was assessed. No significant differences among treatment groups were observed in object exploration or locomotion during the habituation phase. Five days of repeated PCP, AMPH or MK-801 administration selectively and differentially impaired the ability of mice to discriminate a spatial change, while leaving intact the ability to react to a non-spatial change. These data suggest that neurobiological adaptations to drug regimens known to induce psychotic behaviors and alterations in locomotor activity or stereotypies can also alter spatial learning, as assessed in this test, thus indicating that these regimens could also mimic some of the cognitive deficits observed in schizophrenia.

Age Factors↗

PubMed1998

Translocation of protein kinase Cgamma occurs during the early phase of acquisition of food rewarded spatial learning.

This study describes the translocation of the brain specific protein kinase C gamma isoenzyme (PKCgamma) in the hippocampus during food rewarded spatial learning. The holeboard test was used for spatial orientation, and immunoblot analysis was used for assessment of PKCgamma in cytosolic, membrane-inserted and membrane-associated fractions. Membrane-associated PKCgamma was increased during early acquisition of spatial learning, but not in a later phase of training. This transient and apparently temporary intracellular PKCgamma translocation was only observed in the posterior but not in the anterior hippocampus, and was only detected within 10 min after termination of the learning trial. This study supports the idea that PKCgamma is significantly involved in the biochemical events underlying learning and memory, notably during the period of novel information processing. The results further promote the hypothesis that the hippocampus is specifically involved in temporal information processing, which requires the engagement of PKCgamma.

Animals↗