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Behavioral effects of exposure to nuclear magnetic resonance imaging: II. Spatial memory tests.

In order to determine possible effects of exposure to nuclear magnetic resonance imaging (MRI) on cognitive processes, the performance of imaged, sham exposed, and control rats on a spatial memory task was examined. This particular task was chosen because, under some conditions, animals use the magnetic field as a compass when navigating. The rats were required to collect food from eight different locations before returning to an already chosen location. All three groups of rats achieved a high level of performance, and there were no differences between groups in any of the performance measures examined. These results indicate that the MRI procedure has no significant effect on spatial memory processes in rats.

Animals↗

The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes.

The effect of life-long 60% ad lib food restriction on performance in two tasks involving spatial memory, the eight-arm radial maze and the Morris water maze, was studied in young and aged Fischer 344 rats. Restricted (R) and ad lib (AL) feeding groups were compared at 8, 16, and 24 months of age on both tasks. A 30-month-old R group was also tested in the Morris water maze. In the eight-arm maze, although 24-month-old animals performed more poorly than 8- and 16-month-old animals during the first week of testing, overall accuracy of performance did not vary significantly as a function of age. Twenty-four-month-old animals took longer to make 10 choices than did younger animals, and there was a significant interaction between feeding regimen and age, reflecting the fact that at the two younger ages, R groups performed more quickly than the AL groups. In the Morris water maze, both distance swum and time to find the platform increased with age. Life-long food restriction led to small but significant improvements in performance in the water maze in aged rats. R groups showed evidence for better retention over 24-hour intervals than did AL groups. By 30 months of age, however, R animals showed impaired performance relative to younger R groups. These differential findings on the two tasks, as they were used here, suggest that there was greater impairment with age on the spatial memory task requiring retention of information over long intervals than there was on the task primarily involving working memory within a trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Algorithmic behaviour and spatial memory are used by two intertidal fish species to solve the radial maze.

We used an eight-arm radial maze to assess the relative contributions of learned patterns of movement (algorithmic behaviour) and spatial memory to the foraging efficiency of two sympatric rocky-shore fish, fifteen-spined stickleback, Spinachia spinachia, and corkwing wrasse, Crenilabrus melops, exploiting nonrenewable food sources. To forage efficiently, subjects had to avoid arms already depleted within a trial. In the absence of spatial cues, sticklebacks and wrasse improved their foraging efficiency by developing the algorithm of visiting every third arm. In the presence of spatial cues (coloured tiles) algorithmic behaviour was largely subsumed by the use of spatial memory. Imposition of a delay within trials reset the behavioural algorithm, so depressing foraging efficiency in the absence of cues, but not in their presence when memory could be used to guide behaviour. Memory retention for previous choices (working memory) lay within the range 0.5-5.0 min, consistent with the characteristic timescale expected for habitats where prey distribution changes rapidly during the tidal cycle. We considered two hypotheses on the type of information memorized: the cue list hypothesis and the spatial configuration hypothesis. The cue list hypothesis predicts that neither random repositioning nor fixed rotation of spatial cues should impair foraging efficiency, whereas the spatial configuration hypothesis predicts that efficiency should be impaired by random repositioning of cues but not by rotation. Data supported the spatial configuration hypothesis. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Clark's nutcracker spatial memory: many errors might not be due to forgetting

Clark's nutcrackers, Nucifraga columbianarely upon cached seeds for both winter survival and breeding. Laboratory studies have confirmed that nutcrackers use spatial memory to recover their caches. In the laboratory, however, nutcrackers seem to perform less accurately than they do in nature. Two lines of evidence indicate that nutcrackers make 'errors' in the laboratory that are not due to failures of memory. First, when digging in sand-filled cups, nutcrackers were 89% accurate when they plunged their bills directly into the middle of cups but only 21% accurate when they swept their bills across the cups. Second, nutcrackers were more accurate when the cost of probing was increased by covering sand-filled cups with either petri dishes or heavy glass bowls. Birds recovered caches in order of increasing costs. As costs increased, nutcrackers made somewhat fewer errors nearer to cache sites before recovering the caches and dramatically fewer errors further away from cache sites or near cache sites after recovering the caches. Some errors may be a form of environmental sampling. We conclude that the impressive achievements documented by previous studies are underestimates of the spatial memory abilities of Clark's nutcrackers.1997The Association for the Study of Animal Behaviour

Journal Article↗

Changes in open field behavior, spatial memory, and hippocampal parvalbumin immunoreactivity following enrichment in rats exposed to neonatal anoxia.

Behavioral and neurochemical changes following enriched housing were studied in Wistar rats neonatally exposed to anoxia (100% N2 for 25 min at approximately 30 h after birth) or to sham treatment. Neonatal anoxia provoked transient hyperactivity during the P25-P40 period, and spatial memory disturbances persisting into adult life. Enriched housing, from P21, at weaning, to P60, improved behavior in open field and spatial memory abilities in a water maze, reducing the deficits that followed neonatal anoxia. Changes in the expression of the calcium binding protein parvalbumin were present in the CA1, CA3, and DG regions of the hippocampus in both sham-treated and anoxic rats exposed to enrichment. The present findings give further support to the evidence of a positive effect of enriched housing on behavior and learning of normal and lesioned animals, which is sustained by modifications in the neuronal activity, and suggest that modifications in the environment can be useful to counteract the development of some neurological disturbances that follow neonatal insults, e.g., perinatal asphyxia.

Animals↗

Nonredundant roles for hippocampal and entorhinal cortical plasticity in spatial memory storage.

Recently, it has been demonstrated that targeted blockade of the extracellular signal-regulated kinase (ERK) cascade in either the entorhinal cortex (EC) or hippocampus (HIP) results in spatial memory deficits. However, it is unclear if ERK-mediated plasticity in these structures has redundant functions or unique roles. In this report, we contrast the role of long-term plasticity in these two structures with side-by-side comparisons of the effects of PD098059 infusion following water maze training. Analysis of performance during the long-term retention test indicates a role for plasticity in the EC in storing broad location information. In contrast, blocking plasticity in the HIP resulted in deficits in indices of precise location information and goal-directed navigational error. To distinguish between a navigational and location deficit, a "two-room" experimental design was employed. Training in the first room allowed animals to consolidate information regarding navigational strategies prior to training and drug infusion in the second room. Hippocampal-PD098059-infused animals demonstrated behavior suggestive of an expanded representation of the platform location and, thus, a loss of precise location information, suggesting that plasticity in these structures is involved in nonredundant, but complementary, processes necessary for spatial memory.

Animals↗

Internally coherent spatial memories in a mammal.

Children aged 3.5-4.0 years were shown objects being hidden in three different locations in a rectangular environment, were disoriented to disable dead reckoning, and were asked without feedback where each object was. Results showed that children's spatial memories were internally coherents the locations subjects chose were in a correct spatial configuration relative to one another as well as to environmental geometry, despite the fact that the environment's symmetry would have revealed any individual binding of memory for object positions to local environmental features. This finding of internal coherence in the spatial representation of one mammal is discussed relative to neural and behavioral findings on navigation and spatial memory in mammals more generally.

Animals↗

Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice.

The involvement of reduced mastication in senile dementia was evaluated by examining the effect of cutting off the upper molars (molarless) on spatial memory and numbers of hippocampal neurons in aged SAMP8 mice. Molarless mice showed a decrease in both learning ability in a water maze and neuron density in the hippocampal CA1 region compared with control mice. These changes increased the longer the molarless condition persisted. The data suggest a possible link between reduced mastication and hippocampal neuron loss that may be one risk factor for senile impairment of spatial memory.

Aging↗

Neuroanatomical bases of spatial memory.

Although many brain areas have been implicated in spatial memory processes, recent investigations have focused on the hippocampal formation. The present experiment was designed to determine the relative importance of the hippocampal system as compared to the amygdala, the caudate nucleus, or the frontal cortex. Groups of rats were trained to perform on an eight-arm radial maze and then given lesions in one of these brain areas. The post-operative performance of rats with lesions in the fimbria-fornix was never significantly greater than that expected by chance. In contrast, the performance of rats with lesions in the amygdala, the caudate nucleus or the sucal frontal cortex was not significantly different from that of controls. The performance of rats with lesions in the medial frontal cortex was substantially impaired relative to that of the controls during the first few post-operative test sessions, but improved so that by the end of testing the rats were performing as well as were controls. The recovery of function by the rats with lesions in the medial frontal cortex was a function of experience testing on the maze and not simply the passage of time following surgery. Thus, only rats with functional hippocampal systems were able to perform the maze task accurately while thos rats with lesions in the hippocampal system were not.

Amygdala↗

Young and older adults' use of context in spatial memory.

We evaluated the hypothesis that older adults remember spatial information less well than younger adults because they use contextual information less effectively. Young and older adults studied schematic town maps on which structures were presented either simultaneously or successively and on which a network of streets was either present or absent. However, age did not interact with either contextual variable. Thus, we conclude that age differences in spatial memory do not arise from differences in the use of context.

Adult↗

Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats.

Melatonin is an endogenously generated potent antioxidant. Our previous studies indicate that melatonin improved learning and memory deficits in APP695 transgenic mouse of Alzheimer's disease. An ovariectomized (OVX) rat model which is characterized by progressive memory deficits, central cholinergic nerve system degeneration and differentiation/apoptosis imbalance is the ideal in vivo model in which to test the neuroprotective effects of melatonin. OVX Sprague-Dawley rats received daily injections of melatonin (5, 10 and 20 mg/kg) or 17 beta-estradiol (E2, 80 microg/kg) or sesame oil for 16 wk. Morris water maze results showed that ovarian steroid deprivation resulted in spatial memory impairment, while melatonin and E2 significantly ameliorated spatial memory deficits in OVX rats. The latency to find the hidden platform and the distance to reach the platform become shorter in both melatonin and E2-treated rats compared with those that were only OVX. Four months after OVX, the choline acetyltransferase activity in the frontal cortex and hippocampus were greatly decreased in comparison with the controls. Melatonin and E2 antagonized the effects induced by OVX. Interestingly, the activity of the acetylcholinesterase was not altered in any group of rats. DNA fragmentation was presented in the front cortex of the OVX rats. Melatonin and E2 reduced the number of apoptotic neurons. These findings demonstrate the important effects of melatonin and E2 on cholinergic neurons and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Our results indicate that neuroprotection by melatonin partly correlated to modulation of apoptosis and protection of the cholinergic system. Early long-term melatonin application is a promising strategy which could potentially be applied in a clinic setting.

Alzheimer Disease↗

The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze.

The novel neuropeptides orexin-A and orexin-B derive from a common 130-amino acid precursor molecule (prepro-orexin), are mainly localized to neurons within and around the lateral hypothalamus, and exhibit high affinity to the closely related G-Protein-coupled receptors orexin 1 and 2 receptor (OX1R, OX2R). Orexinergic neurons send their axons to the hippocampal formation (CA1, CA2 and dentate gyrus), which expresses OX1Rs. Recent studies have shown that central administration of orexin-A and orexin-B have effects on learning and memory but literature concerning the role of orexinergic system in cognition remains controversial. More recently, antagonists have been described. The most potent and selective is SB-334867-A, which has an affinity of 40 nM at OX1R which is at least 50-fold selective over OX2R. It is likely that the intracerebroventricular (i.c.v.) administration may block OX1Rs in many brain regions. Previously we have shown that intra-CA1 injection of SB-334867-A impairs acquisition, consolidation and retrieval of spatial memory in MWM task. In the present study, the effect of pre-training, post-training and pre-probe of trial intra-DG (dentate gyrus) administration of SB-334867-A (1.5, 3, 6 microg/0.5 microl) on acquisition, consolidation and retrieval in a single-day testing version of MWM (Morris water maze) task was examined. Our results show impaired acquisition and consolidation of MWM task for SB-334867-A as compared with the control group. However, SB-334867-A had no effect on retrieval in spatial memory. Also, this antagonist had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous orexin-A and orexin-B, through DG OX1Rs, play an important role in spatial learning and memory in the rat.

Animals↗

Constraints on priming in spatial memory: naturally learned versus experimentally learned environments.

In four experiments, we explored constraints on priming in spatial memory. In Experiments 1 and 2, subjects who were familiar with the locations of buildings on the Vanderbilt campus participated in a recognition test. The subjects' task was to decide whether or not named buildings were on the campus. Foils in this recognition test were realistic but fictional names of buildings. In principle, the subjects could have performed this task without using spatial knowledge; in fact, they must not have used spatial knowledge, because there was no evidence of priming in recognition as a function of the spatial relations between buildings on the campus. This result differs from those obtained in earlier experiments that have examined memory of spatial layouts learned in laboratory settings. In Experiment 3, the fictional foils were replaced by names of buildings in an area of the campus separated geographically from the main campus. Evidently, this change induced subjects to retrieve spatial knowledge, because the spatial priming effect materialized. A fourth experiment replicated the above findings in a single experiment and demonstrated that spatial priming could be obtained when the configuration of buildings was learned experimentally. These results are explained by appealing to the "decontextualization" that takes place in memory over time.

Adult↗

Acute stress impairs spatial memory in male but not female rats: influence of estrous cycle.

We investigated how sex and estrous cycle influenced spatial recognition memory in the Y-maze after exposure to acute restraint stress. In Experiment 1, intact male and female rats were restrained for 1 h and then 2 h after the start of restraint, rats were trained on the Y-maze. After a 4 h delay, hippocampal-dependent spatial recognition memory was assessed. Acute stress produced opposite patterns between the sexes with spatial memory being impaired in males and facilitated in females. Serum corticosterone measures indicated that both sexes showed a robust corticosterone response after restraint and a moderate corticosterone response after Y-maze exposure. Serum corticosterone levels in response to restraint and Y-maze were not statistically different between the sexes. Experiment 2 examined the influence of the estrous cycle on spatial memory ability after acute stress. Acute stress facilitated spatial memory in females compared to controls, regardless of the estrous cycle phase (estrus and proestrus). Moreover, females in proestrus showed higher serum corticosterone levels during restraint compared to females in estrus. No differences in corticosterone levels were observed at baseline or following 2 h of recovery from restraint. These data show important differences in how sex and estrous cycle influence cognitive functions following acute stress.

Acute Disease↗

Methylene blue restores spatial memory retention impaired by an inhibitor of cytochrome oxidase in rats.

Cytochrome oxidase is the mitochondrial enzyme that catalyzes the utilization of oxygen for the electron transport chain during cellular respiration. Chronic subcutaneous infusion of sodium azide, an inhibitor of cytochrome oxidase, produced a spatial memory retention deficit in rats in a holeboard maze. Methylene blue, which has been shown to increase oxygen consumption in vitro, was used to restore mitochondrial electron transport in order to facilitate memory consolidation. Administration of 1 mg/kg methylene blue after training, during the memory consolidation period, completely restored the memory retention impaired by the inhibitor of cytochrome oxidase. This suggests that methylene blue may compensate for impaired mitochondrial respiration and improve spatial memory retention. Memory retention deficits found in some neurodegenerative diseases may be improved by drugs targeting impaired mitochondrial respiration.

Analysis of Variance↗

Inhibition of poly (ADP-ribose) polymerase and caspase-3, but not caspase-1, prevents apoptosis and improves spatial memory of rats with twice-repeated cerebral ischemia.

The effect of inhibition of PARP [(poly (ADP-ribose) polymerase], caspase-3 and caspase-1 on twice-repeated ischemia-induced apoptosis and memory impairment were examined. The twice repeated ischemia was induced by four-vessel occlusion method in which a 10 min ischemic episode was repeated once after 60 min. The spatial memory was assessed using 8-arm radial maze. The results of this study showed that the repeated ischemia impaired memory and induced apoptosis in hippocampus CA1 field after 7 days. Moreover, 3-aminobezamide (10 mg/kg i.v.), a PARP inhibitor, and Ac-DEVD-CHO (8.4 microg/5 microL i.c.v., bilaterally), a caspase-3 inhibitor, decreased apoptosis by 45% and 58% respectively. Both drugs reduced the error choices, but 3-aminobezamide additionally increased the correct choices and improved the memory when either drug was injected immediately after the ischemic insult. The results also showed that inhibition of interleukin-1beta-converting enzyme, ICE (caspase-1) by Z-ASP-DCB-CH2 (100 microg/kg i.c.v., bilaterally) neither decreased apoptosis (13% reduction) nor improved memory of the ischemic rats. These results suggest that direct inhibition of PARP and caspase-3, but not of caspase-1, prevents apoptosis and improves spatial memory impaired by repeated ischemia.

Animals↗

Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer's disease.

Transgenic mouse models of Alzheimer's disease (AD) have been recently advanced. Tg2576 mice have been shown to develop progressive beta-amyloid (Abeta) neuritic plaques and exhibit impairment of cognitive function. The aim of this study was a better characterization of different aspects of spatial memory performance of transgenic mice, observed at a time when levels of soluble Abeta are elevated and Abeta neuritc plaques start to appear. A general elevation of basal locomotory activity in the home cage was found in Tg2576 mice, which also exhibited an impairment of spontaneous alternation in the Y-maze test. Tg2576 mice were not flexible upon changes in the schedule and failed to codify spatially the testing environment. Consistently, a deficit of spatial memory was also observed when mice were assessed for levels of reactivity to spatial change in the modified open-field test with objects. Compared to controls, Tg2576 mice also exhibited an increased number of explorative approaches to the different objects, and failed to discriminate the displacement of the object. Consistently with the hypothesis of increased disinhibition, a differential behavioural response to the plus-maze paradigm was exhibited by Tg2576 mice. Results clearly indicate that Tg2576 mice are characterized by a number of specific behavioral cognitive alterations, compatible with Alzheimer's disease (AD), which make them a suitable animal model for testing of novel anti-AD drugs.

Alzheimer Disease↗

Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment.

Alzheimer's disease (AD) is characterized by cognitive decline and deposition of beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein exhibits age-related cognitive deficits, Abeta plaque deposition, and oxidative damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich antioxidant, to antagonize the age-related behavioral impairment and neuropathology exhibited by Tg2576 mice. At 8 months of age, 16 female Tg2576 and 15 female wild-type (wt) littermate mice were given ad lib access to tap water or Ginkgo biloba (70 mg/kg/day in water). After 6 months of treatment, all mice received Morris water maze training (4 trials/day for 10 days) to assess hippocampal dependent spatial learning. All mice received a 60-s probe test of spatial memory retention 24 h after the 40th trial. Untreated Tg2576 mice exhibited a spatial learning impairment, relative to wt mice, while Ginkgo biloba-treated Tg2576 mice exhibited spatial memory retention comparable to wt during the probe test. Spatial learning was not different between Ginkgo biloba-treated and untreated wt mice. There were no group differences in learning to swim to a visible platform. Soluble Abeta and hippocampal Abeta plaque burden did not differ between the Tg2576 groups. Brain levels of protein carbonyls were paradoxically elevated in Ginkgo biloba-treated mice. These data indicate that chronic Ginkgo biloba treatment can block an age-dependent decline in spatial cognition without altering Abeta levels and without suppressing protein oxidation in a transgenic mouse model of AD.

Aging↗