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PubMed2004

Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats.

It is well known that neonatal hypoxic-ischemic brain injury leads to mental retardation and deficits in cognitive abilities such as learning and memory in human beings. The ameliorative effect of erythropoietin (Epo) on experimental hypoxic-ischemic brain injury in neonatal rats has been recently reported. However, the effect of Epo on cognitive abilities in the hypoxic-ischemic brain injury model is unknown. The aim of this study is to investigate the effects of Epo on learning-memory, behavior and neurodegeneration induced by hypoxia-ischemia. Seven days old Wistar Albino rat pups have been used in the study (n = 28). Experimental groups in the study were: (1) saline-treated hypoxia-ischemia group, (2) Epo-treated (i.p., 1000 U/kg) hypoxia-ischemia group, (3) sham-operated group, (4) control group. In hypoxia-ischemia groups, left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was induced for 2.5 h. Epo was administered as a single dose immediately after the hypoxia period. When pups were 22 days old, learning experiments were performed using Morris water maze. On the 20th week, when brain development is accepted to be complete, learning experiments were repeated. Rats were then perfused and brains removed for macroscopic and microscopic evaluation. Epo treatment immediately after hypoxic-ischemic insult significantly improved long-term neurobehavioral achievements when tested during the subsequent phase of brain maturation and even into adulthood. Histopathological evaluation demonstrated that Epo also significantly diminished brain injury and spared hippocampal CA1 neurons. In conclusion, Epo administrated as a single dose immediately after neonatal hypoxic-ischemic insult provides benefit over a prolonged period in the still developing rat brain. Since the wide use of Epo in premature newborns, this agent may be potentially beneficial in treating asphyxial brain damage in the perinatal period.

Analysis of Variance↗
PubMed2001

Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation.

If information is stored as distributed patterns of synaptic weights in the hippocampal formation, retention should be vulnerable to electrically induced long-term potentiation (LTP) of hippocampal synapses after learning. This prediction was tested by training animals in a spatial water maze task and then delivering bursts of high-frequency (HF) or control stimulation to the perforant path in the angular bundle. High-frequency stimulation induced LTP in the dentate gyrus and probably also at other hippocampal termination sites. Retention in a later probe test was disrupted. When the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) was administered before the high-frequency stimulation, water maze retention was unimpaired. CPP administration blocked the induction of LTP. Thus, high-frequency stimulation of hippocampal afferents disrupts memory retention only when it induces a change in the spatial pattern of synaptic weights. The NMDA receptor dependency of this retrograde amnesia is consistent with the synaptic plasticity and memory hypothesis.

Afferent Pathways↗
PubMed1996

Spatial memory and navigation by honeybees on the scale of the foraging range

Honeybees and other nesting animals face the problem of finding their way between their nest and distant feeding sites. Many studies have shown that insects can learn foraging routes in reference to both landmarks and celestial cues, but it is a major puzzle how spatial information obtained from these environmental features is encoded in memory. This paper reviews recent progress by my colleagues and me towards understanding three specific aspects of this problem in honeybees: (1) how bees learn the spatial relationships among widely separated locations in a familiar terrain; (2) how bees learn the pattern of movement of the sun over the day; and (3) whether, and if so how, bees learn the relationships between celestial cues and landmarks.

Journal Article↗
PubMed2001

Exploration, anxiety, and spatial memory in transgenic anophthalmic mice.

Contradictory results are found in the literature concerning the role of vision in the perception of space or in spatial navigation, in part because of the lack of murine models of total blindness used so far. The authors evaluated the spatial abilities of anophthalmic transgenic mice. These mice did not differ qualitatively from their wild-type littermates in general locomotor activity, spontaneous alternation, object exploration, or anxiety, but their level of exploratory activity was generally lower. In the spatial version of the water maze, they displayed persistent thigmotaxic behavior and showed severe spatial learning impairments. However, their performances improved with training, suggesting that they may have acquired a rough representation of the platform position. These results suggest that modalities other than vision enable some degree of spatial processing in proximal and structured spaces but that vision is critical for accurate spatial navigation.

Animals↗
PubMedDate not supplied

[Spatial memory in bank voles (Clethrionomys glareolus Schreb) assessed in the cue-controlled open field with the place of refuge].

The capacity of bank voles (Clethrionomys glareolus Schreb) for rapid spatial learning was assessed in cue-controlled open field using their species-specific habits (high fear). Animals were tested in open field after 3 days of pretraining. During testing, novel stimuli (black-and-white geometric figures arranged in symmetric or asymmetric modes for different vole groups) were attached to a curtain surrounding the open field, and a shelter (a familiar box from the home cage) was introduced into the field. Testing consisted of four 10-min trials, the last (probe) trial was performed without the shelter. Time spent in different fielld areas was recorded. The voles remembered previous location of the shelter and preferred to visit this area. It was possible only in the condition with asymmetric arrangement of visual stimuli when animals could use them for navigation. The findings conclude that bank vole have a good capacity for rapid spatial learning.

Animals↗
PubMed1979

The relationship between intelligence and verbal and spatial memory.

Administered the Logical Memory Test (LM) and the Rey-Osterreith Test (RO), which have been assumed to pertain to verbal and spatial cognitive functioning, to 150 Ss referred for neuropsychological screening. Ss also were administered the short version of the WAIS, plus Digit Span. It was found that LM did relate more to verbal IQ than to spatial IQ and vice-versa for RO. It was not clear exactly what aspect of cognitive functioning Digit Span was tapping. The clinical implications of the study are that LM scores must be viewed in the light of verbal IQ level, and RO scores interpreted in relation to both spatial IQ and age. Data are presented that can be used for the statistical interpretation of an individual case test scores.

Adolescent↗
PubMed2006

Spatial memory performance and hippocampal neuron number in osteoporotic SAMP6 mice.

The senescence-accelerated mouse strain P6 (SAMP6) is an inbred mouse that represents a clinically relevant model of senile osteoporosis. However, whether osteoporotic SAMP6 mice have cognitive deficits remains largely unexplored. Here, we used Morris water maze to assess reference memory and working memory performance in SAMP6 mice and SAMR1 controls, at 4 and 8 months of age. In addition, unbiased stereological techniques were used to estimate total neuron number in hippocampal CA1 subfield of the mice used in the behavioral study. Morris water maze test revealed impairments in working memory but not in reference memory of the 4- and 8-month-old SAMP6 mice compared with the SAMR1 mice at the same age. However, there were no significant differences in the total numbers of neurons in hippocampal CA1 subfield when comparing 4-month-old SAMR1 and 4-month-old SAMP6 and 8-month-old SAMR1 and 8-month-old SAMP6, which indicate that, in SAMP6 mice, the structural correlates of working memory deficits are to be found in parameters other than the number of neurons in hippocampal CA1 subfield. These findings suggest that SAMP6 mice exhibit selective cognitive deficits and highlight the importance of this mouse model for studying the brain alterations associated with osteoporosis.

Age Factors↗
PubMed2000

SR 141716A enhances spatial memory as assessed in a radial-arm maze task in rats.

A tonically active endogenous cannabinoid system has been proposed to modulate learning and memory. The purpose of the present study was to determine whether administration of the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR 141716A) would enhance memory as assessed in an eight-arm radial maze task. Because the high degree of choice accuracy in the standard radial-arm maze procedure precludes the possibility of detecting memory enhancement, the difficulty of the task was increased by imposing a delay of varying durations between a two-phase procedure consisting of acquisition and test phases. Significantly fewer errors were committed during the test phase following an injection of SR 141716A than the vehicle treatment. These results provide additional evidence supporting the hypothesis that endogenous cannabinoid systems play a role in memory processes.

Analysis of Variance↗
PubMed2007

Intrastriatal injection of hypoxanthine reduces striatal serotonin content and impairs spatial memory performance in rats.

The aim of this study was to investigate the effects of intrastriatal injection of hypoxanthine, a metabolite accumulated in Lesch-Nyhan disease, on rats' performance in the Morris water maze tasks, along with the monoamine content in striatum of rats. Male adult Wistar rats were divided in two groups: (1) saline-injected and (2) hypoxanthine-injected group. Seven days after solutions infusion, animals were trained in the Morris Water Maze or were sacrificed for evaluation of the striatal monoamine content. Results show that hypoxanthine administration caused impairment on spatial navigation in the acquisition phase in reference memory task in the Morris Water Maze, as well as in the latency to cross over the platform location in probe trial, when compared to the saline group (control). Hypoxanthine also altered rat performance in the working memory. Although striatal dopamine metabolites content did not change, treated animals showed a reduction of tissue levels of serotonin (5-HT) and 5- hydroxyl-indoleacetic acid (5-HIAA). These results show that intra-striatal hypoxanthine administration provoked impairment of spatial learning/memory in rats without affecting striatal dopaminergic system, although serotonergic pathways seem to have been affected.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Electrical induction of spikes in the hippocampus impairs recognition capacity and spatial memory in rats.

In clinical studies, interictal EEG spikes (IS) have been associated with numerous neuropsychological abnormalities, ranging from transitory cognitive impairment to epileptic encephalopathies. Understanding the pathophysiological mechanisms of IS has been hampered by the lack of validated animal models. To mimic IS, a stimulating microelectrode was implanted in the ventral hippocampal commissure and a recording microelectrode in the CA1 region of the hippocampus of normal male rats. Spike patterns were induced using a series of electrical pulses 10-30 ms in duration with a frequency of 0.5-2Hz and a current of 0.2mA. The commissural stimulation-evoked population discharges in the hippocampus resembled naturally occurring IS in epileptic rats and, in no cases, resulted in behavioral seizures. For behavioral testing, the Morris water maze, radial arm maze, and object recognition tasks were used. Spikes were induced during sleep between the two sets of water maze trials; during the trials in the radial arm maze task; and prior to the sample phase and during the delay periods in the object recognition task. We demonstrated that rats that received spikes took longer to reach the escape platform in the second set of water maze trials; had significantly more reference errors and required more trials to complete the radial arm maze task; and had lower investigation ratios in the object recognition task. The results indicate that induction of spikes in the hippocampus results in impairment of spatial reference and nonspatial object recognition memory.

Animals↗
PubMed1978

Loss of hippocampal theta rhythm results in spatial memory deficit in the rat.

Rats learned, using distal room cues, to run to a goal on an elevated, circular track starting from any position on the track. The goal was one of eight equidistant, recessed cups set around the track, the goal cup being distinguished from the others solely by its position in the room. After learning, electrolytic lesions were made in the medial septal nucleus eliminating hippocampal theta rhythm in some animals but not in others. Rats without theta rhythm were no longer able to perform the spatial task, whereas rats with undisturbed theta rhythm retrained normal performance. Although rats without theta rhythm could not find their way directly to the goal, they recognized its location when they came upon it by chance. This type of spatial deficit appears similar to that shown by hippocampally lesioned patient H.M. Subsequent tests demonstrated that rats deprived of theta rhythm before training could nevertheless learn the task.

Animals↗
PubMedDate not supplied

Effects of TCP on spatial memory: comparison with MK-801.

TCP (N-[1-(2-thienyl)cyclohexyl]piperidine), A PCP (phencyclidine) derivative, has been shown to possess antiepileptic and neuroprotective efficacy against chemically induced seizures. However, it is known that other antagonists of the NMDA receptor impair spatial learning. This study was thus undertaken to explore the eventual effects of TCP on memory. The same study was done with MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine ), one of the most studied NMDA receptor antagonists, which can be considered as a reference molecule. Three doses of each drug were chosen: 0.05, 0.1, and 0.2 mg/kg for MK-801 and 0.5, 1, and 2 mg/kg for TCP, the second dosage corresponding to the minimal required for antiseizure activity. The drugs were injected IP 30 min each day before a classical procedure of acquisition in a Morris water maze test. At the highest dose of each drug, the animals did not learn the position of the platform. At 0.1 mg/kg MK-801, the rats used a praxis strategy to find the platform but they did not known where the platform was. Contrary to MK-801, TCP at 1 mg/kg did not induce any memory impairment. At the lowest doses used, no memory impairment was found. It thus appears that, at the minimal therapeutic dose effective against chemically induced seizures (0.1 mg/kg for MK-801 and 1 mg/kg for TCP), TCP, contrary to MK-801, does not induce any memory impairment. Furthermore, at all the doses used, TCP presents the particularity that its locomotor side effects are not long lasting, being no longer observed from 30 min after the injection.

Animals↗
PubMed1999

Influencing of spatial memory in rats by DSP-4 and mescaline.

Behavioural effects of two experimental neurotoxins, mescaline and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), on retention of spatial orientation were studied in the T-maze. The stereotaxic administration of both neurotoxins into the selected brain structures was chosen to reveal this effect. The intensity and time course of the neurotoxic effect were dependent on the brain area administered. Nevertheless, the lengthening of the latencies in reaching the goal was generally more marked after mescaline in comparison with DSP-4.

Animals↗
PubMed2000

Long-term spatial memory in rats with hippocampal lesions.

In animal models of human amnesia, using lesion methods, it has been difficult to establish the role played by the hippocampus in the formation of long-term spatial knowledge. For example, lesions sustained after acquisition have generally produced a flat retrograde amnesia for spatial information. These results have not made it possible to dissociate the participation of the hippocampus in retrieval/performance processes from its participation in consolidation/retention. The present study was designed to investigate if electrolytic hippocampal lesions made before training lead to a deficit in the long-term retention of spatial knowledge when the rats show equal performance levels during the acquisition. Results show that lesioned rats learn a place response just as well as the control rats when, during the training, an intramaze cue orients the animal in its navigation towards the goal arm. One day after reaching criterion, lesioned and control rats remember the task perfectly during a transfer test in which the intramaze signal used previously is not present. However, 24 days later, the hippocampal animals manifest a profound deficit in the retention of the spatial information. When the spatial task learned during the acquisition phase requires only the use of a guidance strategy, control and lesioned animals show the same level of performance during the training phase and the same degree of retention during the retraining phase 24 days after criterion. Taken together, these results suggest that the hippocampus plays a crucial role in long-term retention of allocentric spatial information.

Amnesia↗
PubMed2006

Muscarinic receptor-mediated GTP-Eu binding in the hippocampus and prefrontal cortex is correlated with spatial memory impairment in aged rats.

The present study examined muscarinic receptor/G-protein coupling in the hippocampus and the prefrontal cortex of young and aged Long-Evans rats characterized for spatial learning ability in the Morris water maze. In a highly sensitive time-resolved fluorometry GTP-Eu binding assay, muscarinic-mediated GTP-Eu binding was severely blunted in hippocampus (-32%) and prefrontal cortex (-34%) as a consequence of aging. Furthermore, the magnitude of decreased muscarinic-mediated GTP-Eu binding was significantly correlated with the severity of spatial learning impairment in hippocampus and prefrontal cortex of aged rats and was specifically decreased in the subset of aged rats that were spatial learning impaired when compared to the aged unimpaired and the young rats. Western blot data indicated a preservation of the membrane-bound M1 receptor and the Galphaq/11 protein in both brain regions. These data demonstrate that muscarinic signaling is severely impaired as a consequence of normal aging in a manner that is closely associated with age-related cognitive decline.

Age Factors↗
PubMed1994

Levemopamil injection after cerebral oligemia reduces spatial memory deficits in rats.

Transient reduction of cerebral blood flow to oligemic levels as produced by bilateral clamping of carotid arteries (BCCA) in pentobarbital anesthetized Wistar rats leads to spatial orientation deficiencies in a water maze test 8-10 days after surgery. These deficiencies are more pronounced in 4-month-old than in 6-week-old animals. Levemopamil [(2S)-2-isopropyl-5-(methylphenethylamino)-2-phenylvaleronitril e hydrochloride], a Ca2+ channel blocker and 5-HT2 antagonist, prevents the deficiencies in groups of animals of both ages, even when administered 24 h after the transient vessel occlusion. Levemopamil did not influence the maze performance of sham-operated control rats. Levemopamil, therefore, appears to modulate mechanisms that are altered specifically either by, or as a consequence of, the BCCA procedure. Levemopamil did not influence the altered GABA or ACh content in different vulnerable brain structures following BCCA, showing that the substance acts via additional mechanisms affected by the BCCA procedure.

Acetylcholine↗