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PubMed1998

Spatial memory under acute cold and restraint stress.

This study examined spatial memory as measured by radial arm maze (RAM) performance after exposure to two stress conditions and a normothermic-unrestrained control condition. Male Fischer 344 rats were trained on the win-shift RAM procedure for 7 days, by which time they achieved asymptotic performance. The next day, rats in the two stress groups were exposed to 15 min of restraint in either 37 degrees C water (normothermic-restraint) or in 20 degrees C water (cold-restraint). Rats were then allowed 40 min in a dry cage before being tested in the RAM. Performance was measured using the following dependent variables: number of correct out of the first eight choices, total number of choices, and time per choice. There were statistically significant effects of stress on all these variables; performance decrements were observed in both stress conditions relative to the normothermic-unrestrained condition. Normothermic-restrained rats displayed less impairment than cold-restrained rats on the stress day. Performance of normothermic-restrained rats returned to baseline levels the day after stress, whereas performance for the cold-restrained rats typically did not. This study demonstrates that: 1) restraint and cold stress impair performance on a memory task; and 2) impairment extent is related to stress severity. One of the mechanisms responsible for the observed behavioral deficits under cold stress may involve altered cholinergic function, because we previously demonstrated that hippocampal acetylcholine levels also decrease in relation to the severity of cold stress.

Animals↗

PubMed1986

Exponential decay of spatial memory of rats in a radial maze.

The persistence of spatial memory of rats (n = 14) was investigated in an eight-arm radial maze. The animals were trained until the mean number of errors in the first eight choices was 0.2. The decay of performance with time was studied using delays of 5, 20, 60, 120, or 240 min between choices 4 and 5, during which the animal was removed from the apparatus. A delay of 60 min significantly impaired performance. The mean number of errors was not significantly different from the random choice level after a delay of 120 min. The increase in the number of errors with time was exponential. Comparison of the results with those of previous studies suggests that the nature of training may have effects on memory persistence in the radial maze.

Animals↗

PubMed1999

Development of sex differences in spatial memory.

Males typically perform better than females on tests of spatial abilities. However, Silverman and Eals (1992) found that females can surpass males on certain tasks, in particular recall of object location. This study investigated the age at which females begin having greater recall in object location. Recall was tested with object arrays (sets of line drawings of common objects) using samples of 80 adults (M age = 21 yr.) and 139 children at 3 age groups. Adult data replicated earlier findings, indicating significantly greater recall by women. The samples of children at different ages--4 yr. (n = 43), 10-11 yr. (n = 53), and 15-16 yr. (n = 43)--did not show significant sex differences in this type of recall. The findings suggest that females may surpass males in this spatial ability as adults, apparently due to gradual improvements in spatial memory through childhood and adolescence.

Adolescent↗

PubMed1998

Sigma receptor ligands (+)-SKF10,047 and SA4503 improve dizocilpine-induced spatial memory deficits in rats.

This study examined the effects of the sigma receptor ligands (+)-N-allylnormetazocine ((+)-SKF10,047) and 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) on dizocilpine-induced impairment of working and reference memory in a radial arm maze task in rats. Dizocilpine, a non-competitive NMDA receptor antagonist, significantly impaired both reference and working memory, an effect which was accompanied by ataxia and impairment of food intake. The dizocilpine-induced impairment of reference memory was dose-dependently attenuated by (+)-SKF10,047 and SA4503. SA4503 also attenuated the dizocilpine-induced working memory impairment, although (+)-SKF10,047 had no effect. Neither sigma receptor ligand affected the behavioral symptoms such as ataxia and impairment of food intake induced by dizocilpine. The ameliorating effects of both (+)-SKF10,047 and SA4503 on dizocilpine-induced spatial memory impairment were completely antagonized by a sigma1 receptor antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine-mon ohydrochloride. These results suggest that the interaction of sigma1 receptors with NMDA receptors modulates spatial memory in rats.

Animals↗

PubMed1997

Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on spatial memory and central cholinergic neurons in aged rats.

The effects of a novel prolyl endopeptidase inhibitor (PEP), (S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)- 1-pyrrolidinecar-boxamide (JTP-4819), on performance of the Morris water maze task and on central cholinergic function were investigated in aged rats. Spatial memory (escape latency, path length, and swimming speed to the platform) was impaired in aged rats performing the Morris water maze task when compared to young rats. Administration of JTP-4819 (1 mg/kg, p.o.) for 14 days improved this memory deficit in aged rats, as shown by the decrease in escape latency and path length. In addition, when JTP-4819 (at doses of 1 and 3 mg/kg, p.o.) was administered for 3 wk, it reversed the age-related increase of ChAT activity in the cerebral cortex and the decrease of 3H-choline uptake in the hippocampus. These data suggest that JTP-4819 ameliorates age-related impairment of spatial memory and partly reverses central cholinergic dysfunction, possibly due to the enhancement of neuropeptide function by inhibition of PEP mediated degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone.

Acetylcholine↗

PubMed2005

Nutritional deficits during early development affect hippocampal structure and spatial memory later in life.

Development rates vary among individuals, often as a result of direct competition for food. Survival of young might depend on their learning abilities, but it remains unclear whether learning abilities are affected by nutrition during development. The authors demonstrated that compared with controls, 1-year-old Western scrub jays (Aphelocoma californica) that experienced nutritional deficits during early posthatching development had smaller hippocampi with fewer neurons and performed worse in a cache recovery task and in a spatial version of an associative learning task. In contrast, performance of nutritionally deprived birds was similar to that of controls in 2 color versions of an associative learning task. These findings suggest that nutritional deficits during early development have long-term consequences for hippocampal structure and spatial memory, which, in turn, are likely to have a strong impact on animals' future fitness.

Age Factors↗

PubMed2001

Overlapping mechanisms of attention and spatial working memory.

Spatial selective attention and spatial working memory have largely been studied in isolation. Studies of spatial attention have provided clear evidence that observers can bias visual processing towards specific locations, enabling faster and better processing of information at those locations than at unattended locations. We present evidence supporting the view that this process of visual selection is a key component of rehearsal in spatial working memory. Thus, although working memory has sometimes been depicted as a storage system that emerges 'downstream' of early sensory processing, current evidence suggests that spatial rehearsal recruits top-down processes that modulate the earliest stages of visual analysis.

Journal Article↗

PubMed1996

Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism.

The purpose of the present study was to investigate whether the cannabinoid and cholinergic systems impair working memory through a common mechanism. This hypothesis was tested by examining whether the cannabinoid antagonist SR141716A would ameliorate radial-arm performance deficits caused by either the naturally occurring cannabinoid, delta 9-THC, or scopolamine, a muscarinic antagonist. In addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would prevent delta 9-THC-induced impairment of spatial memory. Finally, because the locomotor suppressive effects of cannabinoids may decrease radial arm choice accuracy independent of a direct effect on memory, we examined the impact of increasing the intertrial error on radial arm choice accuracy. As previously reported, delta 9-THC impaired maze performance (ED50 = 3.0 mg/kg). Increasing the intertrial interval from 5 s to 30 s resulted in a three-fold increase in the amount of time required to complete the maze without affecting choice accuracy. Importantly, SR141716A prevented delta 9-THC-induced deficits in radial-arm choice accuracy in a dose-dependent manner (AD50 = 2.4 mg/kg); however, the cannabinoid antagonist failed to improve the disruptive effects of scopolamine. Conversely, physostigmine failed to improve performance deficits produced by delta 9-THC. These data provide strong evidence that delta 9-THC impairs working memory through direct action at cannabinoid receptors. Moreover, these results suggest that scopolamine and delta 9-THC do not impair spatial memory in a common serial pathway, though they may converge on a third neurochemical system.

Animals↗

PubMed2003

[Morpho-functional changes of neurons in temporal cortex in comparison with spatial memory in bulbectomized mice after treatment with minerals and ascorbates].

The effect of antioxidant mixture of mineralascorbates (MA) on the status of neurons of brain temporal cortex and behavior of mice after olfactory bulbectomy (BE) was studied, as it was previously shown by us that these animals were characterized by a deficit of spatial memory and development of neurodegenerative process in brain structures, which are affected by Alzheimer disease. Disorganization of cytoarchitectonics of temporal cortex with the deletion of its layers as a result of dystrophy of pyramidal neurons and foci of their complete disappearance were shown 1 month after BE. The increased number of neurons with the phenomena of karyopyknosis, karyolysis and vacuolysis was observed with a concomitant reduction in neuronal density. Addition of MA to the diet for three weeks prevented the development of deterioration of spatial memory in mice after BE and protected the neurons of brain temporal cortex from the degenerative changes. The results obtained suggest the possibility of realization of prophylaxis aimed at the prevention of the development of Alzheimer-type neurodestructive processes.

Animals↗

PubMed2005

Chronic treatment with clomipramine and desipramine induces deficit in long-term visuo-spatial memory of rats.

Although the effects of antidepressants in brain neurochemistry have been extensively studied, there are scarce and inconsistent data on the effect of these drugs in learning and memory. The authors studied the effect of daily administration of a single dose of either clomipramine or desipramine, two monoamine-reuptake-inhibitors with preferential serotonergic and noradrenergic profiles, respectively, during 15 days, on the visuo-spatial memory of adults rats measured through their performance in an eight-arm radial maze. Rats receiving 10 mg/kg i.p. daily of clomipramine or desipramine, 30 min before testing, committed a significantly greater number of errors than saline-treated control rats throughout the duration of the test (5 sessions, 15 days), excepting for session one (after 3 days of testing) where there were no differences between the 3 groups of rats. Results indicated that both serotonergic and noradrenergic antidepressants could impair long-term visuo-spatial memory in the rat, whereas inducing no changes in working memory, effects that are likely related to changes in brain monoamine metabolism induced by the antidepressant drugs.

Analysis of Variance↗

PubMed1996

The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.

We have produced a mouse strain in which the deletion of the NMDAR1 gene is restricted to the CA1 pyramidal cells of the hippocampus by using a new and general method that allows CA1-restricted gene knockout. The mutant mice grow into adulthood without obvious abnormalities. Adult mice lack NMDA receptor-mediated synaptic currents and long-term potentiation in the CA1 synapses and exhibit impaired spatial memory but unimpaired nonspatial learning. Our results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories.

Animals↗

PubMed1998

Embryonic entorhinal transplants partially ameliorate the deficits in spatial memory in adult rats with entorhinal cortex lesions.

Our previous studies have demonstrated that axons from grafts of embryonic entorhinal cortex (EC) can reinnervate the deafferented zones in the hippocampus and form synaptic connections with the host dentate gyrus in adult mice and rats deprived of their own entorhinal inputs. Here, we have examined the ability of the EC grafts to ameliorate deficits in spatial memory. Three months after transplantation, the grafted rats and control animals were subjected to Morris water maze testing followed by histological examination. According to the exact position of grafts in the host brain, the rats with lesion and EC transplants were divided into two groups, one with EC grafts contacting both the hippocampus and overlying neocortex (n=7, EC1) and another with EC grafts confined within the hippocampus (n=6, EC2). While EC2 rats were still as impaired as those with lesion and transplants of non-entorhinal cortex (n=10, NEC) or with lesions only (n=7, LES), the EC1 rats performed better than the LES group. In a spatial memory trial, the EC1 group made more crossings over platform site and showed more focused search behavior than EC2, LES, NEC groups. The data suggest that EC grafts could partially ameliorate the deficit in spatial learning behavior in the EC-lesioned adult rats. The requirement for the graft to contact both the neocortex and the hippocampus suggests that the functional effects may be exerted by the formation of new neocortical-EC graft-hippocampal circuits.

Animals↗

PubMed2006

Menhaden fish oil improves spatial memory in rat pups following recurrent pentylenetetrazole-induced seizures.

This study investigated the effects of two supplementary dietary oils (fish oil and corn oil) as parts of isocaloric/isoproteic diets on growth, brain fatty acid composition, and behavior in rat pups with recurrent seizures. Recurrent seizures were induced by injecting rat pups with pentylenetetrazole (PTZ) between P10 (10 days of age) and P14. Either menhaden fish oil (FO) or corn oil (CO) was given as supplemental dietary oil throughout the experiment from P3 to P40. We assessed the effects of the two supplemental dietary oils on spatial memory, histomorphology, and fatty acid composition of brain tissue at the end of the study on P40. Rats that received dietary FO performed significantly better in the Morris water maze, a test used to examine spatial performance in rats; the FO group had significantly shorter escape latencies (P=0.041) during the escape test. Compared with the CO group, the FO group stayed a longer time (P=0.015) and swam a longer distance (P=0.033) in the target quadrant in the spatial probe test. The FO group had significantly higher brain docosahexaenoic acid (P0.01) and significantly lower brain C20:3 n-6 and C20:4 n-6 (P<0.01 and P=0.031) levels compared with the CO group, but the two groups did not differ significantly with respect to neuronal cell loss in the histomorphology study. This study demonstrated that, compared with CO, FO is better in improving spatial memory in rats following recurrent PTZ-induced seizures.

Animals↗

PubMed1985

Effects of opiate antagonists on spatial memory in young and aged rats.

The effects of post-training opiate antagonist administration on spatial memory were assessed in young and aged male Long Evans rats. In Experiment I rats were trained to visit each arm of an eight-arm radial maze once in a session to obtain a food reward placed at the end of each arm. During training aged rats required significantly more trials to achieve criterion performance when compared to young mature rats. However, administration of the opiate antagonist naloxone (2.0 mg/kg) immediately after each training trial did not significantly alter the rate of achieving accurate performance in either age group. In Experiment II young and aged rats that were previously trained to a comparable criterion on the radial maze were tested on the same maze apparatus in novel spatial environments. When animals were exposed to novel spatial information, the effects of post-trial opiate antagonists were examined using a within-subjects counter-balanced design. In Experiment IIa naloxone (2 mg/kg) enhanced the performance of both young and aged rats. In Experiment IIB naltrexone (1.0 mg/kg) was found to have a comparable effect of enhancing the performance of both age groups. In addition, in Experiment IIb a significant age-related deficit was found in rats tested in novel spatial environments. These results indicate that opiate antagonists are capable of improving memory for new spatial information in both young and aged rats on a task that is sensitive to behavioral deficits during normal aging.

Age Factors↗

PubMedDate not supplied

Spatial memory deficit and emotional abnormality in OLETF rats.

Cholecystokinin (CCK) is deeply involved in the control of learning and emotional behaviors. The authors characterize the behavioral properties of Otsuka Long Evans Tokushima Fatty (OLETF) rats, which lack the CCK-A receptor because of a genetic abnormality. In the Morris water-maze task, the OLETF rats showed an impaired spatial memory. In the inhibitory avoidance test, they showed facilitating response 24 h after training. Hypoalgesia was observed in a hot-plate test. In the elevated plus-maze and food neophobia test, OLETF rats showed an anxiety-like response. In addition, OLETF rats were hypoactive in the Morris water-maze and the elevated plus-maze. The results suggest that the OLETF rats showed a spatial memory deficit, hypoactivity and anxiety due, at least in part, to the lack of CCK-A receptors.

Affective Symptoms↗

PubMed1998

A test of spatial memory and its clinical utility in the pre-surgical investigation of temporal lobe epilepsy patients.

Deficits in memory for figurative detail, spatial composition and the spatial location of objects in a scene have been reported postoperatively in right temporal lobectomy patients. The aim of this study was to examine whether these deficits can be used as a sign of lateralised dysfunction in pre-surgical temporal lobe epilepsy (TLE) patients. Sixty-nine patients with lateralised TLE (27 right, 42 left) were assessed on a battery of neuropsychological tests, including tests of general intellectual functioning and psychomotor speed and standardised memory tests involving the learning and recall of verbal and non-verbal material. A new task, the "Aspects of Spatial Memory Test" (AoSMT), based on the experimental tasks developed by Pigott and Milner [39] was also administered. The RTLE and LTLE groups did not differ in their overall level of intellectual function or on measures of cognitive and motor speed. On the AoSMT the LTLE group recognised significantly more figurative detail changes than the RTLE group. In addition, the RTLE group took significantly longer than the LTLE group to identify changes in orientation, figurative detail and filled/unfilled spaces. Poor scores on the AoSMT were significantly correlated with quantitative MRI measures of right hippocampal pathology. The clinical and theoretical implications of these findings are discussed.

Adult↗

PubMed2005

The influence of hippocampal lesions on the discrimination of structure and on spatial memory in pigeons (Columba livia).

Pigeons (Columba livia) were trained with a spatial structural discrimination, which was based on the spatial relationship among the components of a pattern, and a feature-binding structural discrimination, which was based on how different visual features within a pattern were combined. Neither discrimination was impaired by damage to the hippocampus and area parahippocampalis. The lesions impaired performance on a spatial working memory and a spatial reference memory task in open field. The results indicate an intact hippocampus is not essential for the solution of structural discriminations in pigeons and the hippocampus is important for processing some types of spatial information--that used in navigation, but not other types--that used in spatial structural discriminations.

Analysis of Variance↗

PubMed2004

Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior.

Apolipoprotein E4 (apoE4), one of the three most common human apoE (h-apoE) isoforms, is a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. The biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent effect of h-apoE on cognitive performance was studied in gene-targeted mice, which show physiological expression levels and distribution of h-apoE3 or h-apoE4. Male and female h-apoE3 and h-apoE4, apoE-deficient and C57BL/6J mice (4-5 months) were subjected to tasks evaluating spatial memory and avoidance conditioning. Female h-apoE4 mice did not detect changes in the spatial configuration of objects as opposed to female h-apoE3 mice. Female h-apoE3 mice failed to improve their performance during training in a reference memory version of the spatial water-maze task, but performed well during the probe trial 24 h after the last training trial. Memory retention performances of h-apoE4 mice were impaired during this probe trial. Both h-apoE3 and h-apoE4 mice did not improve their performance in a water-maze delayed matching to place task. Finally, h-apoE3 mice showed mild perturbations in a Y-maze active avoidance task, whereas both h-apoE mouse lines performed well in a passive avoidance task. Thus, spatial memory performances appeared particularly sensitive to h-apoE-isoform-dependent effects. Deficits occurred predominantly in female h-apoE4 mice, which support the hypothesis that humans carrying h-apoE4, especially women, have impaired spatial memory compared to those carrying h-apoE3.

Analysis of Variance↗