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PubMed2002

Neurotoxic lesions of the rat perirhinal cortex fail to disrupt the acquisition or performance of tests of allocentric spatial memory.

Rats with neurotoxic lesions of the perirhinal cortex (n = 9) were compared with sham controls (n = 14) on a working memory task in the radial arm maze. Rats were trained under varying levels of proactive interference and with different retention intervals. Finally, performance was assessed when the maze was switched to a novel room. None of these manipulations differentially impaired rats with perirhinal lesions. Rats were next trained on delayed matching-to-place in the water maze. Even with retention delays of 30 min, there was no evidence of a deficit. Although interactions between the perirhinal cortex and hippocampus may be important for integrating object-place information, the perirhinal cortex is often not necessary for tasks that selectively tax allocentric spatial memory.

Animals↗

PubMed2003

Exploring the limits of spatial memory in rats, using very large mazes.

In Experiment 1, rats foraged for food in six successive phases with 8, 16, 24, 32, 40, and 48 arms attached in random locations to a large radial maze. The percentage of novel choices appeared to be determined more by spatial proximity than by number of arms. In Experiment 2, rats foraged for food in four successive phases with 8, 16, 24, and 48 arms attached to the maze in spread-out or tight configurations. Performance was poor in the tight configurations regardless of the number of arms. Performance was excellent in the 8-arm spread-out condition but declined as 16 and, then again, 24 arms were added. Thus, spatial separation, not number of locations, was the chief determinant of performance in the first two experiments. In Experiment 3, in successive phases, 8, 16, 24, 32, 40, 48, 16, and 8 food towers were set in a circle on the floor, with the spatial separation between adjacent towers held constant at 33 cm. The percentage of novel choices declined as 8 towers became 16 and did not change again with 24, 32, 40, or 48 towers in place but then increased again as 16 towers became 8. In Experiment 4, in successive phases, 8, 16, 24, and 32 food towers were set in a circle, with the spatial separation between adjacent towers held constant at 66 cm. The percentage of novel choices declined as 8 towers became 16 and again as 16 towers became 24 but did not decline further. These data were discussed in terms of the fundamental problems posed by variations in the number of food locations in the pursuit of the limit of spatial memory in rats.

Animals↗

PubMed1987

Entorhinal transplants and spatial memory abilities in rats.

Transplants of embryonic entorhinal tissues, placed into the angular bundle region of adult rats, innervate appropriate areas of the host hippocampal formation and amygdala, provided that native entorhinal connections have been destroyed. In the present study, transplants were examined for their ability to restore spatial memory abilities which are lost following the bilateral destruction of native entorhinal connections. Animals were tested for their ability to perform an 8-arm radial maze task, for spontaneous alternation in a T-maze, and for their ability to learn to alternate in a T-maze for a food reward. Animals with lesions, and those with lesions + implants, remained impaired on all 3 tasks examined for as long as 6 months postimplantation. During this time, no transplant-induced behavioral recovery was observed, although behavioral stabilization was observed on the spontaneous alternation task at 6 months post-transplantation. The data suggest that these transplants may be limited in their ability to restore functions which are highly dependent upon the anatomical integrity of the damaged circuits and the precise organization of information flow through the damaged area.

Amygdala↗

PubMed2006

Dietary phytoestrogens enhance spatial memory and spine density in the hippocampus and prefrontal cortex of ovariectomized rats.

Long-term maintenance of ovariectomized rats (9 weeks) on chow containing high phytoestrogen levels (Purina LabDiet 5001) as compared to chow with minimal phytoestrogens (Harlan 2016 Teklad) was associated with better performance of the spatial memory task, object placement, increased dendritic spine density in CA1 and prefrontal cortex pyramidal neurons, and higher uterine weights. Object recognition memory, anxiety on an elevated plus maze and body weight were unaffected by phytoestrogen levels in the diet.

Administration, Oral↗

PubMed2005

Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury.

Erythropoietin (EPO) is neuroprotective in models of stroke and traumatic brain injury (TBI) when administered prior to or within the first few hours after injury. We seek to demonstrate that EPO also has neurorestorative effects when administered late (i.e., 1 day) after TBI in the rat. Twelve rats were subjected to TBI. Six rats were treated with EPO daily for 14 days starting 1 day after injury, and an additional six rats were treated with saline. Bromodeoxyuridine (BrdU) was administered daily for 14 days. Memory tests using a Morris Water Maze were performed prior to and after injury and treatment. Animals were sacrificed at 15 days after TBI, and their brains were prepared for histological analysis of damage to the dentate gyrus (DG) and for evaluation of newly formed neurons using double labeling of BrdU and MAP-2. The data revealed a significant improvement in spatial memory and significant increase in the number of newly formed neurons with EPO treatment compared with control animals. These data suggest that EPO treatment initiated 1 day after TBI is neurorestorative by enhancing neurogenesis, as well as neuroprotective.

Animals↗

PubMed2004

Selective hippocampal damage in rhesus monkeys impairs spatial memory in an open-field test.

The hippocampus is critical for remembering locations in a wide variety of species, including humans. However, recent findings from monkeys following selective hippocampal lesions have been equivocal. To approximate more closely the situations in which rodents and birds are tested, we used a spatial memory task in which rhesus monkeys (Macaca mulatta) moved about freely in a large room, on a tether. We used MRI-guided stereotaxic surgery to produce selective hippocampal lesions in five monkeys, and retained five unoperated control monkeys. In the study phase of each trial of the matching-to-location task, monkeys found food in one site in an array of identical foraging sites. During the test, which occurred after a delay, monkeys could return to the site where the food had been found during study to obtain more food. In Experiment 1, normal monkeys showed a small significant tendency to return directly to a site where they had previously found food that day. Operated monkeys showed no such matching tendency. In Experiment 2, further training produced reliable matching-to-location performance in both groups at short delays, but monkeys with selective hippocampal lesions rapidly forgot the location of the food. In Experiment 3, we tested whether monkeys used a "cognitive map" to encode the location of the hidden food, by requiring them to relocate the food from a starting location different from that used during study. As a group, monkeys were more accurate than expected by chance, indicating that they did encode the rewarded location with respect to allocentric landmarks; however, both groups of monkeys were significantly worse at relocating the food when required to approach from a different location. In Experiment 4, probe trials using symmetrical test arrays found no evidence for egocentric coding of the rewarded location.

Animals↗

PubMed2001

Differential effects of glucose on modulation of emotional and nonemotional spatial memory tasks.

Research examining the memory-enhancing effects of glucose in humans has been limited to mnemonic tasks lacking affective components, even though glucose may be a mechanism for emotion-induced memory enhancement. This limitation does not permit analysis of interactions between the enhancing properties of emotional stimuli and glucose. Participants were administered either glucose or saccharin 15 min prior to completing a neutral or emotional spatial memory task. Performance under three glycemic conditions (100 mg/kg or 50 g glucose, or placebo) for the two sets of emotional stimuli revealed a significant interaction. Both 100-mg/kg and 50-g doses of glucose resulted in impaired performance for emotional stimuli. For neutral stimuli, a 100-mg/kg dose enhanced memory, whereas a 50-g dose showed no effect. Results indicate that the enhancing effects of emotional stimuli may be attenuated by the consumption of glucose and suggest that recent food consumption should be considered in paradigms examining memory.

Adult↗

PubMed1993

Effects of acidic fibroblast growth factor on cholinergic neurons of nucleus basalis magnocellularis and in a spatial memory task following cortical devascularization.

The ability of acidic fibroblast growth factor to elicit a trophic response in the nervous system of the rat was tested in vitro and in vivo. Treatment of cultured septal cells with acidic fibroblast growth factor resulted in an elongation of glial processes as assessed by immunostaining for glial fibrillary acidic protein. Increased choline acetyltransferase was also observed. The responses to acidic fibroblast growth factor in vivo were studied in rats trained in a spatial memory task, using the Morris water maze. Randomly selected animals were subjected to unilateral cortical devascularization. This lesion results in partial unilateral infarction of the neocortex, and in retrograde degeneration of the nucleus basalis magnocellularis. Animals were tested post-lesion for memory retention and were then killed for morphological studies. Intracerebroventricular administration of acidic fibroblast growth factor (0.6 microgram/h for seven days starting at surgery) prevented the lesion-induced impairment in this test, and reduced the nucleus basalis magnocellularis cholinergic degeneration, as assessed by morphometric choline acetyltransferase-like immunoreactivity and radioenzymatic assay for choline acetyltransferase activity. The preservation of the phenotype of injured cholinergic neurons of the nucleus basalis magnocellularis by acidic fibroblast growth factor was indicated by the maintenance of the cross-sectional area of cell bodies and mean length of neuritic processes one month after surgery. The effect of acidic fibroblast growth factor in non-cholinergic cells remains to be investigated. It is suggested that acidic fibroblast growth factor may alleviate the lesion-induced deficit in the memory retention task by preventing disruption of functional connections between nucleus basalis magnocellularis and intact cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Dietary cis-fatty acids that increase protein F1 phosphorylation enhance spatial memory.

Activation of protein kinase C (PKC) facilitates long-term potentiation (LTP), a model of memory, and increases its substrate protein F1 (aka GAP43) phosphorylation in direct relation to synaptic enhancement. Unsaturated fatty acids (c-FAs) which activate purified PKC, when injected into hippocampus, enhance LTP. To determine if dietary c-FAs could alter memory itself as well as brain PKC substrate (F1) metabolism, rats were maintained for 10 weeks on fatty acid diets enriched in mono-unsaturated oleic acid (OA; 20% olive oil, w/w), or a mono- and di-unsaturated mixture of oleate/linoleate (O/L; 20% corn oil), or a saturated fatty acid diet of laurate/myristate (L/M; 20% hydrogenated coconut oil). The O/L diet group was superior to the OA and L/M groups in spatial memory performance after the first two weeks of acquisition and in later achievement of criterion performance. The O/L diet had a significantly higher hippocampal protein F1 in vitro phosphorylation than in both the OA and L/M in trained and non-trained animals. Significantly, animals that made fewer errors showed higher F1 phosphorylation (r = -0.70). Diet both increases brain PKC substrate phosphorylation and enhances maze learning, confirming the feasibility of enhancing learning and memory by dietary regimens derived from basic neurochemical studies of synaptic plasticity.

Animals↗

PubMed1994

Characterization of high voltage spindles and spatial memory in young, mature and aged rats.

EEG was recorded from rats of three age groups, and high voltage spindles (HVS) were measured during waking immobility. Total mean spindling times in 4- (young), 10- (mature) and 22- (aged) month-old rats were 0.3 +/- 0.1, 20.4 +/- 7.4 and 33.4 +/- 14.9 s, respectively. Spatial memory was assessed in these rats using a discrimination version of the Morris water maze. Performance (as measured by number of choice errors) was compared with the extent of HVS activity by characterizing rats as "spindling" if the total average duration of HVS discharges exceeded 5 s, and "non-spindling" if these discharges averaged less than 5 s. Spindling and nonspindling rats had similar performance during training; however, on a 14-day retention trial, spindling rats had a significantly higher mean error score of 2.8 +/- 0.5 compared with 1.2 +/- 0.3 for nonspindling rats (p = 0.011). These results show that spindling activity increases in mature and aged rats, and that HVS discharges may be an electrophysiological change that parallels the progression of brain dysfunction associated with memory impairment.

Action Potentials↗

PubMed1990

Development of reference and working spatial memory in preschool children.

Three groups of preschool children (aged 18 to 28, 33 to 42, and 47 to 58 months) were given a radial search test similar to the radial arm maze used with nonhuman subjects. The children searched for chocolate sweets among 10 labeled locations in a room, 5 of which were baited with a sweet. Older children outperformed the intermediate group, who in turn outperformed the youngest group in requiring fewer choices to retrieve all of the sweets. Working memory and reference memory aspects of performance were then separated: Reference memory (restriction of choices to the baited subset) in older children was superior to that in the youngest group but not to that in the intermediate group. In terms of working memory (avoidance of repeat responses to already visited locations), the older group made fewer errors than the intermediate group, who, in turn, made fewer errors than the youngest group. We concluded that working and reference components of spatial memory in children may share common elements, perhaps the ability to recognize places as familiar, although reference memory may develop earlier than working memory.

Attention↗

PubMed2006

Vagus nerve stimulation does not affect spatial memory in fast rats, but has both anti-convulsive and pro-convulsive effects on amygdala-kindled seizures.

Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy. Using a seizure-prone Fast-kindling rat strain with known comorbid behavioral features, we investigated the effects of VNS on spatial memory, epileptogenesis, kindled seizures and body weight. Electrodes were implanted in both amygdalae and around the left vagus nerve of 17 rats. Following recovery, rats were tested in the Morris water-maze utilizing a fixed platform paradigm. The VNS group received 2 h of stimulation prior to entering the Morris water-maze. Rats were then tested in the kindling paradigm wherein the VNS group received 2 h of stimulation prior to daily kindling stimulation. Finally, the abortive effects of acute VNS against kindling-induced seizures were determined in fully kindled rats by applying VNS immediately after the kindling pulse. Body weight, water consumption and food intake were measured throughout. Memory performance in the Morris water-maze was not different between control and vagus nerve stimulation rats. Similarly, kindling rate was unaffected by antecedent VNS. However, pro-convulsive effects (P<0.05) were noted, when VNS was administered prior to the kindling pulse in fully kindled rats. Yet, paradoxically, VNS showed anti-convulsant effects (P<0.01) in those rats when applied immediately after the kindling stimulus. Body weight was significantly lower throughout kindling (P<0.01) in VNS-treated rats compared with controls, which was associated with reduced food intake (P<0.05), but without difference in water consumption. VNS appears to be devoid of significant cognitive side effects in the Morris water-maze in Fast rats. Although VNS exhibited no prophylactic effect on epileptogenesis or seizure severity when applied prior to the kindling stimulus, it showed significant anti-convulsant effects in fully kindled rats when applied after seizure initiation. Lastly, VNS prevented the weight gain associated with kindling through reduced food intake.

Amygdala↗

PubMed1999

Cerebral hypoperfusion yields capillary damage in the hippocampal CA1 area that correlates with spatial memory impairment.

The impact of chronic cerebral hypoperfusion on cognitive function and cerebral capillary morphology in the hippocampus was examined. Young adult Wistar rats were subjected to permanent ligation of both common carotid arteries (two-vessel occlusion). One month after vascular occlusion, a small but non-significant impairment in the acquisition of spatial information was registered compared with sham-operated controls. Two months after surgery, the occluded animals displayed an impaired performance throughout the training period. One year after surgery, the acquisition curves demonstrated a significant attenuation of the learning rate in the occluded rats group, whereas no significant differences in long-term retention were observed. Thus, chronic hypoperfusion induced by two-vessel occlusion gave rise to impairment of spatial memory. Following behavioural testing, the rats were killed at the age of 17 months, and capillaries in the CA1 and dentate gyrus were examined using transmission electron microscopy. Typical age-related capillary abnormalities such as degenerative pericytes and thickened basement membranes (with or without fibrosis) were detected in the hippocampus of sham animals. In occluded rats, the occurrence of capillaries displaying such abnormalities almost doubled in the CA1 region, but was similar in the dentate gyrus, compared with sham controls. A highly significant correlation was found between the last Morris maze performance and the percentage of capillaries with deposits in the basement membrane in the hippocampal CA1 area of occluded rats, which was not present in the sham animals. We conclude that a long-term hypoperfusion accelerated the development of age-related ultrastructural aberrations of capillaries in the hippocampal CA1 area, but not in the dentate gyrus. Thus, not only neurons, but also capillaries in the hippocampal CA1 area are sensitive to an impaired microcirculation. Moreover, the cognitive performance of hypoperfused rats correlated closely with the condition of the capillaries in the CA1 area, suggesting that capillary integrity is one of the important determinants of brain function in conditions that compromise cerebral microcirculation.

Animals↗

PubMed1995

Spatial memory deficits, increased phosphorylation of the transcription factor CREB, and induction of the AP-1 complex following experimental brain injury.

Traumatic brain injury causes both short- and long-term neurological impairments. A cascade of biochemical changes triggered by the injury may increase the expression of several genes, which has been hypothesized to contribute to the observed cognitive deficits. The mechanism(s) of induction for these genes is not yet known. We present evidence that lateral cortical impact injury in rats that produces spatial memory deficits also increases phosphorylation of the transcription factor CREB (cAMP response element binding). Subsequent to the phosphorylation of CREB, c-Fos expression and the AP-1 complex are enhanced. The temporal and spatial activation of c-Fos is consistent with it being induced by phosphorylated CREB proteins. Thus, CREB-mediated gene activation may contribute to the observed behavioral deficits. Further elucidation of the biochemical and pathophysiological changes will be of importance for clinical therapy.

Animals↗

PubMed2006

Hyperforin prevents beta-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-beta-deposits.

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (Abeta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Abeta-induced spatial memory impairments and on Abeta neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Abeta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Abeta oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Abeta aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.

Alzheimer Disease↗

PubMed2000

Genetic differences in response to novelty and spatial memory using a two-trial recognition task in mice.

A two-trial memory task, based on a free-choice exploration paradigm in a Y-maze, was previously developed to study recognition processes in Sprague-Dawley rats. Because this paradigm avoids the use of electric shock or deprivation that may have nonspecific effects and does not require learning of a rule, it may be particularly useful for studying memory in mice. Four inbred strains (Balb/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57BL/6 x SJL/J), and one outbred strain (CD1) were used to validate this task in mice and to characterize a strain distribution in response to novelty and working memory. Exploration was measured with a short (2 min) intertrial interval (ITI) between acquisition and retrieval, while memory was examined with longer intervals (30 min, 1 h, and 2 h). A study of the time course of the response to novelty revealed varying degrees of preference and/or habituation to novelty among the different strains, with CD1 exhibiting a very high response to novelty and others showing lower (C57 x SJL hybrids) to complete absence (SJL) of exploration of novelty. Memory span, assessed with increasing ITIs, varied widely among strains from 30 min (C57 x SJL hybrids) to at least 2 h (C57 and BALB). Such demonstrated sensitivity to a wide range of behavioral phenotypes supports the use of this spatial memory task as an effective tool for the study of genetic influences on the response to novelty and recognition processes in mice.

Animals↗

PubMed1994

Comparing matching ability, spatial memory, and ideational fluency in boys and girls.

The purpose of our study was to examine whether girls and boys show patterns of problem-solving ability similar to those attributed by Kimura in 1992 to women and men, respectively. Subjects were 28 girls and 24 boys, aged 5-11 years, who were tested individually on matching ability, spatial memory, and ideational fluency, tasks on which women reportedly outperform men. No significant gender differences in these problem-solving abilities were found. On ideational fluency, the youngest girls were seven times more likely than young boys to give whimsical responses, but older girls were then times less likely than older boys to give whimsical responses. These results suggest that the patterns of visuospatial problem-solving abilities that Kimura ascribed to women and men are not present in preadolescent girls and boys.

Aptitude↗

PubMed2003

Sexual orientation related differences in spatial memory.

The purpose of this study was to investigate and extend previously reported sex differences in object location memory by comparing the performance of heterosexual and homosexual males and females. Subjects were 240 healthy, right-handed heterosexual and homosexual males and females. They were instructed to study 16 common, gender-neutral objects arranged randomly in an array and subsequently tested for object recall, object recognition and spatial location memory. Females recalled significantly more objects than males, although there were no group differences in object recognition. Decomposition of significant interactions between sex and sexual orientation on spatial location memory (controlling for differences in object recall, age and IQ) revealed that heterosexual females and homosexual males scored better than heterosexual males, and no different from each other. There were no differences between homosexual and heterosexual females. The findings suggest that homosexual males and heterosexual females encode, store and retrieve positional and relational information about spatial layouts similarly, pointing to within-sex variations in the neural architecture underlying spatial memory.

Female↗