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Results for “Spatial Learning”

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PubMed1995

Distinct components of spatial learning revealed by prior training and NMDA receptor blockade.

Synaptic plasticity dependent on N-methyl-D-aspartate (NMDA) receptors is thought to underlie certain types of learning and memory. In support of this, both hippocampal long-term potentiation and spatial learning in a watermaze are impaired by blocking NMDA receptors with a selective antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5) or by a mutation in one of the receptor subunits. Here we report, however, that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug. This is not because of stimulus generalization, and occurs despite learning of the second task remaining hippocampus dependent. An AP5-induced learning deficit is, however, still seen if the animals are pretrained using a non-spatial task. Thus, despite its procedural simplicity, the watermaze may involve multiple cognitive processes with distinct pharmacological properties; although required for some component of spatial learning, NMDA receptors may not be required for encoding the spatial representation of a specific environment.

2-Amino-5-phosphonovalerate↗

PubMed2003

Spatial learning in rats is impaired after degeneration of the nigrostriatal dopaminergic system.

We investigated spatial learning in rats with unilateral and bilateral lesions of the nigrostriatal dopaminergic system. We used the Morris water maze paradigm, which tests spatial forms of learning and memory and allows discrimination between sensory-motor and learning disabilities. Animals were trained preoperatively to learn the location of a spatially fixed hidden platform to escape from the swimming pool (acquisition training). A visual and a probe test were used before and after the acquisition training, respectively. Our results show that animals with unilateral lesions, although displaying longer escape latencies, have normal spatial memory abilities. Animals with bilateral lesions were able to swim as fast or even faster than animals with unilateral lesion. Despite the fact that these animals had learned the spatial navigation tasks preoperatively, bilateral dopaminergic lesions led to a profound deficit in ability to find a hidden platform during an acquisition task. In general, animals with bilateral lesions persisted in swimming along the pool walls and their spatial navigation performance during a probe test was very poor. These results suggest that deficit of the nigrostriatal dopaminergic system can affect the selection and maintenance of behavioral strategies in spatial navigation.

Animals↗

PubMed1998

Hippocampal dynorphin B injections impair spatial learning in rats: a kappa-opioid receptor-mediated effect.

The hippocampus plays a central role in the acquisition and storage of information. Long-term potentiation in the mossy fibre pathway to the CA3 region in the hippocampus, an animal model of memory acquisition, is modulated by dynorphin peptides. This study investigated the possible role of hippocampal dynorphin in spatial learning. Male rats were trained in the Morris Water Task after microinjection with different doses of dynorphin B (1, 3.3 or 10 nmol/rat) or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Dynorphin B was found to impair spatial learning at all tested doses. The synthetic kappa1-selective opiate receptor antagonist nor-binaltorphimine (2 nmol) also given into the hippocampus fully blocked the acquisition impairment caused by dynorphin B (10 nmol), while nor-binaltorphimine alone did not affect learning performance. These findings suggest that dynorphin peptides could play a modulatory role in hippocampal plasticity by acting on hippocampal kappa-receptors and thereby impair spatial learning.

Animals↗

PubMed2000

Repeated acquisition and performance chamber for mice: a paradigm for assessment of spatial learning and memory.

Molecular genetic manipulation of the mouse offers the possibility of elucidating the function of individual gene products in neural systems underlying learning and memory. Many extant learning paradigms for mice rely on negative reinforcement, involve simple problems that are relatively rapidly acquired and thus preclude time-course assessment, and may impose the need to undertake additional experiments to determine the extent to which noncognitive behaviors influence the measures of learning. To overcome such limitations, a multiple schedule of repeated acquisition and performance was behaviorally engineered to assess learning vs rote performance within-behavioral test session and within-subject utilizing an apparatus modified from the rat (the repeated acquisition and performance chamber; RAPC). The multiple schedule required mice to learn a new sequence of door openings leading to saccharin availability in the learning component during each session, while the sequence of door openings for the performance component remained constant across sessions. The learning and performance components alternated over the course of each test session, with different auditory stimuli signaling which component was currently in effect. To validate this paradigm, learning vs performance was evaluated in two inbred strains of mice: C57BL/6J and 129/SvJ. The hippocampal dependence of this measure was examined in lesioned C57BL/6J mice. Both strains exhibited longer latencies and higher errors in the learning compared to the performance component and evidenced declines in both measures across the trials of each session, consistent with an acquisition phenomenon. These same measures showed little or no evidence of change in the performance component. Whereas three trials per session were utilized with C57BL/65 mice in each component, behavior of 129/SvJ mice could only be sustained for two trials per component per session, demonstrating differences in testing capabilities between these two strains under these experimental conditions and thus precluding the ability to make systematic strain comparisons of learning capabilities. Hippocampal lesions in C57BL/6J mice resulted in substantially longer latencies and increased errors in the learning but not the performance component, demonstrating the importance of this region to spatial learning as measured in the RAPC. In aggregate, this positive reinforcement-based operant paradigm to evaluate murine spatial learning detects strain differences and hippocampal dependence and permits explicit differentiation of the impact of noncognitive contributions to learning measures on a within-subject, within-session basis.

Animals↗

PubMed2004

Spatial learning transiently disturbed by intraventricular administration of ouabain.

The presence of sodium-potassium-adenosine triphosphatase (Na+,K+-ATPase) on the surface of arachnoid cells indicates that active transport of electrolytes and water occurs there. Previously, we accidentally found that intraventricular administration of TGF-beta1 impaired rat spatial learning. Levels of Na+,K+ -ATPase were decreased in arachnoid cells with fibrosis. To characterize the role of the Na+,K+ -ATPase, Wistar rats were intraventricularly administered a total of 200 microl of ouabain, at concentrations of 10(-5), 10(-4) and 10(-3) M, for one week with an osmotic pump, and were examined with a Morris water maze. Latency for reaching the platform did not significantly differ between ouabain-administered rats and controls. Spatial learning was impaired in a dose-dependent manner. Na+,K+ -ATPase activity of arachnoid cells ceased during ouabain administration, and recovered completely three weeks after the end of ouabain administration. The present results suggest that the Na+,K+ -ATPase on the surface of arachnoid cells contributes to maintenance of rat spatial learning.

Animals↗

PubMed2000

DNA fragmentation factor 45 deficient mice exhibit enhanced spatial learning and memory compared to wild-type control mice.

Programmed cell death or apoptosis is a highly regulated physiological process that is critical in development, particularly in the central nervous system. The DNA fragmentation factor 45 (DFF45 or ICAD) is a subunit of a heterodimeric DNase complex that is crucial for DNA fragmentation and normal apoptosis. To examine the neurobiological consequences of lacking DNA fragmentation and timely apoptosis during mouse development in vivo, we compared spatial learning behaviors in DFF45 mutant and wild-type control mice. We found that DFF45 mutant mice exhibit enhanced spatial learning and memory compared to wild-type mice. Moreover, both the granule cell density and total granule cell number in the hippocampal dentate gyrus region are higher in the DFF45 mutant brains than in the wild-type brains. We propose that the increase in granule cell number in the dentate region due to the DFF45 mutation changes the neuronal network underlying spatial learning and memory in DFF45 mutant mice.

Animals↗

PubMed2000

Spatial learning induced changes in expression of the ryanodine type II receptor in the rat hippocampus.

Calcium signaling critical to neural functions is mediated through Ca(2+) channels localized on both the plasma membrane and intracellular organelles such as endoplasmic reticulum. Whereas Ca(2+) influx occurs via the voltage- or/and ligand-sensitive Ca(2+) channels, Ca(2+) release from intracellular stores that amplifies further the Ca(2+) signal is thought to be involved in more profound and lasting changes in neurons. The ryanodine receptor, one of the two major intracellular Ca(2+) channels, has been an important target for studying Ca(2+) signaling in brain functions, including learning and memory, due to its characteristic Ca(2+)-induced Ca(2+) release. In this study, we report regional and cellular distributions of the type-2 ryanodine receptor (RyR2) mRNA in the rat brain, and effects of spatial learning on RyR2 gene expression at mRNA and protein levels in the rat hippocampus. Using in situ hybridization, reverse transcription polymerase chain reaction, and ribonuclease protection assays, significant increases in RyR2 mRNA were found in the hippocampus of rats trained in an intensive water maze task. With immunoprecipitation and immunoblotting, protein levels of RyR2 were also demonstrated to be increased in the microsomal fractions prepared from hippocampi of trained rats. These results suggest that RyR2, and hence the RyR2-mediated Ca(2+) signals, may be involved in memory processing after spatial learning. The increases in RyR2 mRNA and protein at 12 and 24 h after training could contribute to more permanent changes such as structural modifications during long-term memory storage. Zhao, W., Meiri, N., Xu, H., Cavallaro, S., Quattrone, A., Zhang, L., Alkon, D. A. Spatial learning induced changes in expression of the ryanodine type II receptor in the rat hippocampus.

Animals↗

PubMed2003

Longitudinal axis of the hippocampus: both septal and temporal poles of the hippocampus support water maze spatial learning depending on the training protocol.

It has been suggested previously that 30% sparing of the hippocampus is enough to support spatial learning of a reference memory task in a water maze provided the spared tissue is located septally (Moser et al. 1995, Proc Natl Acad Sci USA 92:9697-9701). Therefore, the temporal hippocampus may not be involved in spatial memory. Place cells are also found in this part of the structure, and it has been suggested that these place cells have larger, less well-tuned place fields than are found in the septal hippocampus. We tested the possibility that the temporal hippocampus might be involved in spatial learning when the animals are required to distinguish between different contexts. Experiment 1 was a replication of the findings reported by Moser et al., using their protocol (8 trials/day, 6 days) and the groups with 20-40% hippocampus spared septally or temporally (volume assessed by quantitative volumetric techniques). In experiment 2, rats with also 20-40% sparing of the hippocampus either septally or temporally were trained in two water maze concurrently (four trials/day/water maze, 8 days). Rats with 20-40% hippocampus spared temporally were able to learn the two water maze tasks normally, and no difference was observed between rats with septal and temporal hippocampus spared across different measures of performance. In experiment 3, rats with 20-40% hippocampus spared septally or temporally were trained in one water maze as in experiment 1, but using a spaced training protocol similar to that of experiment 2 (four trials/day, 8 days). Rats with temporal hippocampus spared developed a preference for the training quadrant and acquired levels of performance indistinguishable from those of rats with septal hippocampus spared. The results suggest that the temporal hippocampus can support the learning of two, but also one, spatial water maze reference memory task, provided the training protocol is adequate.

Animals↗

PubMed1995

Effects of a period of asphyxia during birth on spatial learning in the rat.

The present study aimed to test whether an acute period of asphyxia during birth in the rat results in long-term alterations in CNS function. Morphologic studies have indicated that the hippocampus is particularly vulnerable to perinatal anoxia. Thus, the present study tested adult rats, which had undergone acute birth asphyxia, for their performance in spatial learning and memory tasks associated with the hippocampus. Rat fetuses on the day of birth were submitted to an acute period of complete asphyxia by submersion of the isolated uterus into a water bath for 5-20 min before delivery of the pups. Control animals were either born vaginally or delivered by rapid cesarean section. At 1.5 mo of age, rats that had undergone 15 min of birth asphyxia showed no deficit in acquisition of spatial learning, measured as latency to find a hidden platform in the Morris water maze. However, at 4 mo of age, separate groups of rats, which had undergone 10, 15, or 20 min of birth asphyxia, showed a deficit in initial acquisition of the spatial learning task compared with vaginally born controls, whereas the 5-min group performed similarly to controls. After overtraining, there was no difference among groups on short-term (1 wk) retention of the spatial navigation task; however, asphytic animals tested at 1.5 mo and retested at 4 mo showed a slight deficit in retention on retest. Animals that had undergone 15 min of birth asphyxia weighed less than did vaginally born animals, but showed no deficit in swimming ability, spontaneous alternation in a T maze, or other sensorimotor indices.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Alterations of behavior and spatial learning after unilateral entorhinal ablation of rats.

The entorhinal cortex (EC) is the key input and output structure of the hippocampus. It plays a crucial role in sensory processing, memory and learning, as well as in mechanisms of epileptic seizures. Our previous studies on the 4-aminopyridin induced epilepsy model of rats showed that ablation of unilateral EC prompted weakening of limbic seizure manifestation, thus the possibility of therapeutical benefit of this kind of surgery can be risen. Open field, elevated plus-maze and Morris water-maze test were performed to analyze changes of the basal activity level, exploratory behavior, and spatial memory capacity, respectively, of adult Wistar rats having undergone left EC excision. Compared with the sham-operated control group, rats with lesions of the EC showed enhanced locomotor activity in the open-field test. The elevated plus-maze test revealed higher frequency of entries and more time spent in the open arms. Morris water-maze test suggested impairment of the spatial learning capacity following left lateral EC lesion. Therefore, our data showed that EC lesions induced hyperactivity, increased exploratory behavior, and impaired spatial learning. Entorhinal cortex ablation, as a potential method for controlling epileptic seizures has multiple effects on animals' behavior and spatial learning. To determine the cost-benefit ratio of a potential surgical intervention needs further experimental and human investigations.

Animals↗

PubMed2005

Short photoperiods impair spatial learning and alter hippocampal dendritic morphology in adult male white-footed mice (Peromyscus leucopus).

Although seasonal changes in brain morphology and function are well established in songbirds, seasonal plasticity of brain structure and function remain less well documented in mammals. Nontropical animals display many adaptations to reduce energy use to survive winter, including cessation of reproductive activities. Because of the high energetic costs of brain tissue, we hypothesized that male white-footed mice (Peromyscus leucopus) would reduce brain size in response to short days as well as regress their reproductive systems. Because short days may decrease hippocampal volume and impair spatial learning and memory in rodents and because of the potential for seasonal plasticity in the hippocampus, we hypothesized that photoperiod alters hippocampal morphology to affect spatial learning and memory. Mice housed in either long or short days for 10 weeks were examined for performance in a water maze; brains were then removed and weighed, and hippocampal volumes were determined. We also measured dendritic morphology and spine density in the CA1, CA3, and dentate gyrus. Short days decreased brain mass and hippocampal volume compared with long days. Short days also impaired long-term spatial learning and memory relative to long days but did not affect sensory discrimination or other types of memory. Short days decreased apical (stratum lacunosum-moleculare) CA1 spine density, as well as increased basilar (stratum oriens) CA3 spine density. Results from this study suggest that photoperiod alters brain size and morphology, as well as cognitive function. Understanding the mechanisms mediating these photoperiod-induced alterations may provide insight for treatment of seasonal cognitive and affective disorders.

Analysis of Variance↗

PubMed1989

Low doses of atropine sulfate impair retention of a well-learned spatial task.

Retention of a well-learned spatial task was assessed in rats 10 minutes prior to, and 10, 20, 30, 40, and 50 minutes after treatment with 3, 10 or 30 mg/kg, iv, atropine sulfate or the equivalent volume of saline, iv. There was a variable dose effect for escape latency and choice accuracy measures of spatial retention. A relatively large dose of atropine sulfate (30 mg/kg, iv) significantly impaired choice accuracy and escape latency compared with the control group. Moreover, impairment in choice accuracy was observed with smaller doses of atropine sulfate (3, 10 mg/kg, iv) than have previously been shown to disrupt spatial retention.

Animals↗

PubMed1989

The effects of ibotenic acid lesions of the nucleus accumbens on spatial learning and extinction in the rat.

Rats with ibotenic acid lesions of the nucleus accumbens (N. Acc) were studied in two spatial learning paradigms: a T-maze and a Morris water maze. Learning of a spatial discrimination task and its reversal in the T-maze were disrupted by the N. Acc lesions. As both original and reversal learning were impaired, there was no evidence of a specific lesion effect on reversal learning. The lesioned rats did not perseverate excessively in their choice of the previously reinforced arm. There was evidence of behavioural inflexibility during extinction when the lesioned rats failed to slow the pace at which they ran the maze in the absence of reward. Spontaneous alternation was not significantly affected by the lesion. Acquisition of the second spatial task, locating the hidden platform in the Morris water maze, was also impaired. The lesioned rats did eventually learn the task and successfully reached the platform with similar latencies and heading errors to controls. Thus, the N. Acc lesion impaired but did not abolish spatial learning in the T-maze and the water maze. The deficits observed in this study may reflect a role for the N. Acc in the reorganisation of behaviour in response to external change.

Animals↗

PubMed2003

Effect of antisense oligonucleotide of noggin on spatial learning and memory of rats.

AIM: To investigate the effect of antisense oligonucleotide (ASODN) of noggin on rat spatial learning and memory. METHODS: Expression of noggin mRNA was measured by in situ hybridization method and the ability to spatial learning and memory was tested with Morris water maze. RESULTS: Compared with control rats, noggin mRNA positive neurons in dentate gyrus (DG) and CA3 region of hippocampus were markedly increased after the Morris water maze training (P<0.01). The increase of noggin mRNA positive neurons in hippocampus following maze training could be significantly blocked by icv injection of antisense noggin ODN, and the injection also impaired the learning and memory formation as compared to that in control rats. But the sense oligonucleotide (SODN) had no effect. CONCLUSION: Noggin, as an embryonic gene expressed in adult hippocampus, plays an important role in the process of learning and memory formation.

Animals↗

PubMed2006

Experience-dependent regulation of zif268 gene expression and spatial learning.

Environmental enrichment (EE) is known to enhance the cognitive ability of rodents. To translate EE to the human condition, it is important to understand the parameters of its efficacy. In this study, we examine if the cognitive enhancement associated with EE is permanent and whether a developmental window exists for its efficacy. Rats were housed in continuous isolation (ISO), continuous enrichment (EE), enrichment from postnatal day (PN) 21-50, and then isolation from PN50-79 (PM), or isolation from PN21-50 and then enriched from PN50-79 (CW). Spatial learning ability and basal expression of the immediate-early genes zif268 and Arc as well as the NR1 subunit of the NMDA receptor were assessed. Rats housed in an enriched environment at the time of testing (EE and CW) performed significantly better in the spatial learning task than rats housed in an isolated environment at the time of testing (ISO and PM). Enhanced performance in the spatial learning task was associated with a higher expression of zif268 only in the CA3/CA4 region of the hippocampus. Our study further defines parameters that make environmental enrichment effective in enhancing learning performance and the findings may be helpful in the translation of this intervention to the human condition.

Animals↗

PubMed1991

Spatial learning in two inbred strains of mice: genotype-dependent effect of amygdaloid and hippocampal lesions.

Spatial learning performance and maze-running strategies were estimated in two inbred strains of mice, C57BL/6 and DBA/2, submitted to an 8-arm radial maze task. Subsequently the genotype-dependent effect of hippocampus and amygdala on the mastering of this task was examined as a function of the different acquisition model provided by each strain. The results firstly show that unoperated C57BL/6 mice reach a higher level of performance and develop a stronger preference for adjacent arms - 45 degrees angle - turns than unoperated DBA/2 mice. In the high learner C57BL/6 strain, both hippocampal and amygdaloid lesions impair performance and modify maze-running strategies. With practice, however, the difference between amygdala-lesioned mice and controls disappears while that between hippocampus-lesioned mice and controls persists. Conversely, in the low learner DBA/2 strain, hippocampal lesions have a negative effect on a single parameter of performance, while amygdaloid lesions only affect maze-running strategies. Taken together, these results confirm the specific control exerted by the hippocampus on spatial learning. Moreover, they suggest that the amygdala can parallel the role of the hippocampus as far as the baseline level of performance of the strain considered is high.

Amygdala↗

PubMed1995

Reduced hippocampal CA1 Ca(2+)-induced long-term potentiation is associated with age-dependent impairment of spatial learning.

Expression of Ca(2+)-induced CA1 long-term potentiation (LTP) was analysed in hippocampal slices obtained from (1) 3-month-old and (2) 18-20-month-old Sprague-Dawley rats selected for their performances in the Morris water maze task. In all slices, a transient (10 min) increase of extracellular Ca2+ concentration (4 mM) caused a long-lasting enhancement of potentials evoked by electrical stimulation of radiatum fibers. However, a significant difference was found in the degree of potentiation among groups. In particular, increases of the CA1 response amplitudes were significantly lower in old rats impaired in spatial learning than in young at 30 (P < 0.05), 60, 90 and 120 min (P < 0.01) after restoring the normal Ca2+ concentration. On the contrary, no differences were observed between young animals and the old ones with good performances in spatial learning. The data suggest that amplitude of CA1 Ca(2+)-induced LTP in old rats is related to spatial learning abilities.

Aging↗

PubMedDate not supplied

Effects of gestational and lactational exposure to TCDD or coplanar PCBs on spatial learning.

Recently we reported that in utero and lactational exposure to specific ortho-substituted polychlorinated biphenyl (PCB) congeners resulted in a learning deficit on a delayed spatial alternation (DSA) task in female rats. In this study, spatial learning and memory was assessed following in utero and lactational exposure to coplanar PCBs or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Time-mated Sprague-Dawley rats were dosed with PCB 77 (3,3',4,4'-tetrachlorobiphenyl), 2 or 8 mg/kg/day; PCB 126 (3,3',4,4',5-pentachlorobiphenyl), 0.25 or 1.0 micrograms/kg/day; TCDD, 0.025 or 0.1 micrograms/kg/day; or corn oil vehicle via gavage on gestation days 10-16. Litters were culled to eight on day 2 and weaned on day 21. Beginning on day 80, one male and one female from each litter were tested on an eight-arm radial maze working memory task. The TCDD-exposed rats displayed pronounced decreases in errors relative to controls. PCB 77- and PCB 126-exposed rats showed similar, but less pronounced, decreases in errors. The same animals were later tested on a T-maze DSA task, but no differences among groups were observed. In conclusion, perinatal exposure to low doses of TCDD or structurally related coplanar PCBs appeared to facilitate acquisition of a working memory task on the radial arm maze. This effect was very different from that previously observed in rats exposed to ortho-substituted PCB congeners. The rats exposed to ortho-substituted PCBs did not differ from controls on the radial arm maze and were impaired on the T-maze DSA task. Together these findings suggest that coplanar and ortho-substituted PCBs may have different mechanisms of action on the CNS.

Animals↗