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PubMed1993

Regional specificity of raphe graft-induced recovery of behavioral functions impaired by combined serotonergic/cholinergic lesions.

We compared the effects of embryonic raphe grafted into either the hippocampus or the entorhinal cortex on the ability of rats to perform a spatial memory water-maze task. Serotonin depletion or partial cholinergic lesion of the hippocampus (by injection of colchicine into the septum) did not affect the ability of rats to perform the task, but the combined treatment did. Double-lesioned rats, with raphe grafts in the hippocampus, but not in the entorhinal cortex, performed similar to control or single-lesioned rats. The results suggest that the functioning of the serotonergic innervation of the hippocampus, and not of its afferents, is crucial for the ability of rats to perform spatial memory tasks, especially when the septohippocampal cholinergic connection is disrupted.

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

Effects of perinatal exposure to aspartame on rat pups.

Possible effects of perinatal exposure to L-aspartyl-L-phenylalanine methyl ester (aspartame) on rat pups were investigated. Adult female rats, and later their pups, were exposed, via their drinking water, to aspartame (0.007%, 0.036%, 0.18% or 0.9% w/v) or phenylalanine (0.45% w/v) for 12 days prior to conception until the pups were 38 days old. Control rats were given plain water. The adults exposed to aspartame consumed an average of 14, 68, 347 and 1614 mg/kg/day of aspartame and those exposed to phenylalanine consumed an average of 835 mg/kg/day of phenylalanine. After weaning the pups given aspartame consumed an average of 32, 154, 836, and 3566 mg/kg/day of aspartame and those given phenylalanine consumed an average of 1795 mg/kg/day of phenylalanine. No effect of aspartame or phenylalanine was detected on either two measures of morphological development (i.e., latencies to pinnae detachment and eye opening) or two tests of reflex development (i.e., latencies for surface righting at 7 days of age and negative geotaxis at 8 days of age). All groups were similar in spatial memory as assessed with two different mazes with pups 30-36 days old. The number of arms before reentry in an 8-arm radial-arm maze and the acquisition curves from a milk maze did not differ between groups. Furthermore, the latencies of mothers to retrieve their litters was also unaffected by the aspartame and phenylalanine. These results indicate that perinatal exposure to aspartame, when voluntarily consumed by mothers (14-1614 mg/kg/day) and later directly by the rat pups (32 to 3566 mg/kg/day) does not affect reflex development, morphological development or spatial memory.

Animals↗
PubMed1994

Direct measurement of brain temperature during and after intraischemic hypothermia: correlation with behavioral, physiological, and histological endpoints.

The aim of the present study was to evaluate critically the protection afforded by hypothermia against ischemic injury to the hippocampus. Hypothermic treatment was applied selectively to the brain during a 5 min carotid artery occlusion in gerbils. Following a period of recovery, two independent measures were used to assess hippocampal function: (1) an open field test of spatial memory (assessment was made during the first 10 d after ischemia) and (2) measurement of evoked potentials from area CA1 in hippocampal slices (3 weeks after the ischemic episode). The functional outcome portrayed by these tests was compared to a morphological evaluation of CA1 pyramidal cells at three rostrocaudal levels. All evaluations were carried out in the same animals. We found converging evidence that intraischemic hypothermia provides virtually complete protection against a 5 min episode of cerebral ischemia. Animals treated with hypothermia performed as well as sham-operated controls in a spatial memory task, had field potentials that were indistinguishable from normal animals and CA1 cells appeared normal when assessed histologically. In contrast, ischemia at normothermia resulted in a deficit in open field behavior (p < 0.01), diminished field potentials in stratum radiatum (p < 0.01), and near total loss of pyramidal cells in dorsal CA1 (p < 0.01). There was a remarkably high correlation between these diverse measures (r ranged from 0.7 to 0.9, p < 0.01), which provides strong support for the use of hypothermia as an effective treatment for ischemia. This study introduces a novel approach for the evaluation of putative anti-ischemic treatments: combining behavioral, electrophysiological, and histological measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury.

OBJECT: Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects, such as promoting angiogenesis, increasing fibrinolysis, and reducing inflammatory responses, and has shown promise in enhancing recovery in animals with traumatic brain injury (TBI) and stroke. The authors tested the effect of atorvastatin on vascular changes after TBI. METHODS: Male Wistar rats subjected to controlled cortical impact injury were perfused at different time points with fluorescein isothiocyanate (FITC)--conjugated dextran 1 minute before being killed. Spatial memory function had been measured using a Morris Water Maze test at various points before and after TBI. The temporal profile of intravascular thrombosis and vascular changes was measured on brain tissue sections by using a microcomputer imaging device and a laser confocal microscopy. The study revealed the following results. 1) Vessels in the lesion boundary zone and hippocampal CA3 region showed a variety of damage, morphological alterations, reduced perfusion, and intraluminal microthrombin formation. 2) Atorvastatin enhanced FITC-dextran perfusion of vessels and reduced intravascular coagulation. 3) Atorvastatin promoted the restoration of spatial memory function. CONCLUSIONS: These results indicated that atorvastatin warrants investigation as a potential therapeutic drug for TBI.

Animals↗
PubMed2006

[Effects of neonatal recurrent seizures on gamma-aminobutyric acid B1 receptor expression in the rat brain].

OBJECTIVE: This study investigated the effects of flurothyl-induced neonatal recurrent seizures on gamma-aminobutyric acid B1 receptor (GABAB1R) expression in neonatal and adult rat brain, and explored the possible relationship between the alterations of GABAB1R in mature brain and the changes of spatial memory and seizure susceptibility in adult rats. METHODS: Forty-eight postnatal day (P) 7 Sprague-Dawley rats were randomly assigned into two groups: Control and Seizure group (n=24 each). Seizures were induced by inhalant flurothyl daily for six consecutive days in rat pups from the Seizure group. Twelve rats selected randomly in each group were sacrificed on the 7th day after the last seizure for detecting the expressions of GABAB1R mRNA and protein in cerebral cortex and hippocampus by reverse transcription-polymerase chain reaction (RT-PCR) and immuno-histochemistry method. The spatial memory was tested by using the Morris water maze task during P61 to P64 and the seizure threshold was measured at P75 following intraperitoneal injection of pentylenetetrazol ( PTZ ) in the remaining rats. The rats were then sacrificed for detecting the expressions of GABAB1R mRNA and protein in cerebral cortex and hippocampus. RESULTS: The expressions of GABAB1R mRNA and protein in the cerebral cortex on the 7th day after the last seizure and at P75 decreased significantly in the Seizure group when compared with the Control group (P < 0.05). The GABAB1R protein expression in the dentate gyrus on the 7th day after the last seizure in the Seizure group was significantly lower than that in the Control group (P < 0.05), but the GABAB1R mRNA expression in the hippocampus was not different from that in the Control group. There were no significant differences in the expressions of GABAB1R mRNA and protein in the hippocampus between the two groups at P75. The escape latencies in water maze of the rats in the Seizure group at P64 were significantly longer than those in the Control group (98,533.8 +/- 27,205.4 ms vs 46,723.3 +/- 40,666.5 ms; P <0.05). There were no differences in the seizure threshold between the two groups. CONCLUSIONS: The expressions of GABAB1R mRNA and protein in the cerebral cortex and hippocampus of neonatal rats with recurrent seizures decreased significantly, suggesting the changes of GABAB1R may be related to acute brain injury following neonatal recurrent seizures and the memory deficit in adult rats caused by neonatal recurrent seizures.

Animals↗
PubMed2007

Changes in brain oxidative metabolism induced by water maze training.

Although the hippocampus has been shown to be essential for spatial memory, the contribution of associated brain regions is not well established. Wistar rats were trained to find a hidden escape platform in the water maze during eight days. Following training, the oxidative metabolism in different brain regions was evaluated using cytochrome oxidase histochemistry. Metabolic activations were found in the prelimbic cortex, cornu ammonis (CA) 1 subfield of the dorsal hippocampus and the anterior thalamic nuclei, relative to yoked swim controls and naïve rats. In addition, many cross-correlations in brain metabolism were observed among the latter regions. These results support the implication of a hippocampal-prefrontal-thalamic system to spatial memory in rats.

Animals↗
PubMed2003

Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex.

This study compared the effects of lesions damaging hippocampus-related pathways in anterior thalamus (AT) and parahippocampal (PH) cortex on allocentric spatial memory. Rats were trained to perform radial maze delayed nonmatching (DNM) with random selection of arms to prevent egocentric solutions. After experimental treatment (control, excitotoxic AT, radiofrequency PH, or combined AT-PH lesions), rats were retrained for 30 sessions from 2 to 8 weeks after surgery. Results showed comparable impairments for AT and PH lesions that added without interaction in the combined AT-PH group. During chronic recovery, the AT-PH group exhibited delay-dependent deficits comparable to previous results for hippocampal lesions. Thus, AT and PH lesions appear to have separate effects that together disrupt hippocampus-dependent spatial memory.

Animals↗
PubMed2005

Disruption of delayed memory for a sequence of spatial locations following CA1- or CA3-lesions of the dorsal hippocampus.

Axon-sparing neurotoxic lesions of CA1 or CA3 were produced in the dorsal hippocampus to test dissociative lesion effects on spatial working memory for sequential items. Rats were required to remember four different sections sequentially presented on a newly devised maze (i.e., Tulum maze) during a study phase. Each section was cued by a unique object that was specifically associated with each location within the section during the study phase. Following a 15-s delay and during the test phase, rats were required to revisit the location within a section randomly chosen among the previously visited sections in the absence of the cued object. Both CA1 and CA3 lesions similarly disrupted accurate relocation of a previously visited place. However, differential effects of the CA1 and CA3 lesions were observed in serial position curves. CA3-lesions disrupted performance for the first three serial positions, but did not disrupt performance for the last serial position (recency). In contrast, CA1-lesions disrupted performance for all serial positions. The results suggest that temporal separation of spatial memory may depend on the conjoint function of CA1 and CA3 of the hippocampus with a disruption of a spatial pattern completion process following CA3 lesions and a disruption of a temporal pattern separation process following a CA1 lesion.

Animals↗
PubMedDate not supplied

Age diminishes performance on an antisaccade eye movement task.

Tthe antisaccade eye movement task, which has been linked to frontal lobe function, presents a target in one visual field and asks subjects to move their eyes to the same location in the opposite field. The task requires inhibition of the reflexive prosaccade to the cue, initiation of the antisaccade to the opposite field, and visuo-spatial memory of the cue location. Forty-two subjects from 19-79 years of age performed this task and a control task, visually guided saccades to the cue itself, to determine which functions are affected by aging. The time to initiate antisaccades increased linearly with age at a rate greater than the time to initiate visually guided saccades. This difference suggests that the processing time to inhibit the incorrect movement to the cue is selectively increased with age. Older subjects also made more incorrect prosaccadic movements to the cue, a finding consistent with the loss of inhibitory processing capacity. The accuracy of movements did not change, which suggests that visuo-spatial memory is unaffected by aging.

Adolescent↗
PubMed1987

Developmental aspects of memory for spatial location.

The purpose was to show whether or not the encoding of location met criteria defining an automatic process (L. Hasher & R. T. Zacks, 1979, Journal of Experimental Psychology: General, 108, 356-388; 1984, American Psychologist, 39, 1372-1388). Among other criteria, automatic processes are not expected to show developmental changes beyond an early age, to be unrelated to intelligence level, and to be unaffected by instructions. In the first experiment preschool through sixth-grade children were compared on a 40-picturebook task following incidental (remember the names of pictures) or intentional (remember location) instruction. Subjects viewed and named pictures in sets of four, arranged in quadrants in the opened book, and then attempted to recall names of the objects pictured and to relocate pictures on blank pages. In the second experiment, second and sixth graders, college students, elderly persons, and mentally retarded persons were compared on a 60-picturebook task following either incidental or semantic incidental instructions (give the function of objects pictured). Memory for location was invariant across age groups and intelligence level. The only exception was that 3 and 4 year olds were more accurate following intentional instructions. Otherwise there were no differences between intentional and incidental instructions. Semantic instructions resulted in slightly more accurate locations. The results were interpreted as supportive of the Hasher and Zacks' automaticity hypothesis.

Child↗
PubMed1995

Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia.

BACKGROUND AND PURPOSE: Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils. METHODS: The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated. RESULTS: Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia. CONCLUSIONS: Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia.

Animals↗
PubMed2003

The effect of (+/-)-CP-101,606, an NMDA receptor NR2B subunit selective antagonist, in the Morris watermaze.

It is well established that the NMDA receptor antagonists block hippocampal long-term potentiation and impair acquisition in the Morris watermaze task, although the role of individual NMDA receptor subtypes is largely unknown. In the present study, we compared the effects of (+/-)-CP-101,606, an antagonist selective for NMDA receptor NR1/NR2B subunit-containing receptors and the nonselective NMDA receptor antagonist MK-801, on acquisition in the Morris watermaze. Male hooded Lister rats were given 4 trials/day to find a fixed hidden platform submerged beneath the opaque water of the Morris watermaze. Twenty-four hours after the last acquisition trial, a 'probe trial' was conducted to assess the rat's spatial memory for the location of the hidden platform. Those rats treated with MK-801 (0.1 mg/kg, i.p.) 60 min prior to the acquisition and probe trials took significantly longer to find the hidden platform during training and spent significantly less time searching the platform's location during the probe trial than vehicle-treated rats. In contrast, 60-min pretreatment with (+/-)-CP-101,606 (60 mg/kg, p.o.), a dose that fully occupied hippocampal NR1/NR2B subunit-containing receptors, as determined by ex vivo NMDA receptor-specific [3H]ifenprodil binding immediately following watermaze experiments, had no effect on acquisition or the probe trial. These results suggest that antagonists selective for NR1/NR2B subunit-containing receptors may not impair spatial memory in rats in the Morris watermaze.

Administration, Oral↗
PubMed1978

Delayed alternation in rats after pre- or postcommissural fornicotomy.

Contribution of the pre- and postcommissural fornices to short-term spatial memory was investigated in rats by evaluating the effect of small electrolytic lesions, located stereotaxically, with texts of reinforced alternation in a T-maze. Lesions in the postcommissural fornix were without behavioral effect. Animals with lesions that damaged the precommissural fornix were temporarily impaired in alternation with massed trials. They largely recovered their efficiency by the end of five postoperative sessions. Both the interpolation of irrelevant vestibular input (rotation) and lengthened intertrial intervals (1-4 min) reinstated an alternation deficit that had recovered in the massed-trial condition of testing. It is suggested that the recovery did not represent relearning to alternate but represented experience-dependent switching to parallel neural circuits that also mediate short-term spatial memory.

Animals↗
PubMed2002

Psychomotor performance after short-term anaesthesia.

BACKGROUND AND OBJECTIVE: The aim was to examine the immediate effects of short-term anaesthesia on the different components of psychomotor performance of the upper extremity and cognitive functions, and to find out if there were any differences in the sensitivities of the different tests. The measured psychomotor aspects were simple reaction time, choice reaction time, speed of movement, index finger-tapping speed, co-ordination, visual spatial memory capacity, digit-symbol substitution and the Maddox Wing test. METHODS: The subjects were 30 female patients aged 24-50 yr who had been through a minor gynaecological operation. Anaesthesia had been induced with propofol and alfentanil. The measurements were mainly made with the HPM/BEP system, and the tests were performed 1 h before the anaesthesia and immediately after the wake-up. RESULTS: Short-term anaesthesia prolonged the simple reaction time by 7% and the choice reaction times by 25% (one-choice) and 7% (two-choice) and decreased the speed of movement by 10% (one-choice) and 19% (two-choice), index finger-tapping speed by 7% and co-ordination by 7%. In addition, visual spatial memory capacity decreased by 21%, digit-symbol substitution increased by 5% and the Maddox Wing test increased by 68%. CONCLUSIONS: Based on the results, it seems that short-term anaesthesia reduces both signal processing at the central level, and motor control and co-ordination of movements at the peripheral level, and has a decreasing effect on motor performance in the above-mentioned aspects measured immediately after wake-up.

Adult↗
PubMed1991

Induction of transverse polarity by blue light: an all-or-none response.

Phototropic stimulation induces a spatial memory. This was inferred from experiments with maize (Zea mays L.) coleoptiles involving opposing blue-light pulses, separated by variable time intervals, and rotation on a horizontal clinostat (Nick and Schafer, 1988b, Planta 175, 380-388). In those experiments, individual seedlings either curved towards the first or towards the second pulse, or they remained straight. Bending, if it occurred, seemed to be an all-or-none response. Intermediates, i.e. plants, bending only weakly, were not observed. In the first part of the present study it was attempted to create such intermediates. For this purpose the strength of the first, inducing, and the second, opposing, pulse was varied. The result was complex: (i) Individual seedlings maintained the all-or-none expression of spatial memory. (ii) However, on the level of the whole population, the time intervals at which a given response type dominated depended on the fluence ratio. (iii) Furthermore, the final curvature was determined by the fluence ratio. These results are discussed in terms of a blue-light-induced transverse polarity. This polarity initiates from a labile precursor, which can be reoriented by an opposing stimulation (indicated by the strong bending towards the second pulse). The strong curvatures towards the first pulse over long time intervals reveal that, eventually, the blue-light-induced transverse polarity becomes stabilised and thus immune to the counterpulse. In the second part of the study, the relation between phototropic transduction and transverse polarity was characterised by a phenomenological approach involving the following points: (i) Sensory adaptation for induction of transverse polarity disappears with a time course similar to that for phototropic sensory adaptatation. (ii) The fluence response for induction of transverse polarity is a saturation curve and not bell-shaped like the curve for phototropism (iii) For strong counterpulses and long time intervals the clinostat-elicited nastic response (Nick and Schafer 1989, Planta 179, 123-131) becomes manifest and causes an "aiming error" towards the caryopsis. (iv) Temperature-sensitivity of polarity induction was high in the first 20 min after induction, then dropped sharply and rose again with the approach of polarity fixation. (v) Stimulus-summation experiments indicated that, for different inducing fluences, the actual fixation of polarity happened at about 2 h after induction. These experiments point towards an early separation of the transduction chains mediating phototropism and transverse polarity, possibly before phototrophic asymmetry is formed.

Cell Polarity↗
PubMed2001

Impaired spatial working memory across saccades contributes to abnormal search in parietal neglect.

Visual neglect of left space following right parietal damage in humans involves a lateral bias in attention, apparent in many search tasks. We hypothesized that parietal neglect may also involve a failure to remember which locations have already been examined during visual search: an impairment in retaining searched locations across saccades. Using a new paradigm, we monitored gaze during search, while simultaneously probing whether observers judged they had found a new target, or judged instead that they were re-fixating a previously examined target. A patient with left neglect following focal right parietal infarction repeatedly re-fixated right locations. Critically, he often failed to remember that these locations had already been searched, treating old targets as new discoveries at an abnormal rate. In comparison, healthy age-matched control subjects rarely re-fixated targets, and mistook old targets as new targets even more rarely. The frequency of such mistakes in the parietal patient, for different conditions, correlated with the severity of his neglect. Control experiments indicated no perceptual localization deficit in non-search tasks. These results suggest a deficit in retaining searched locations across saccades in parietal neglect, in addition to the lateral spatial bias. Moreover, the former deficit exacerbates the latter, such that patients do not realize that the rightward locations favoured by their bias have already been examined during previous fixations and, for this reason, they saccade back to them repeatedly. The combination of the two deficits (a lateral bias plus a deficit in retaining locations already searched) may thus explain the pathological pattern of search that characterizes parietal neglect: why stimuli on the right are re-examined recursively, as if being searched for the first time, and hence why stimuli on the left continue to be ignored even with unlimited viewing time. These proposals accord with recent electrophysiological and functional imaging data, demonstrating posterior parietal involvement in the retention of target locations across saccades.

Aged↗
PubMedDate not supplied

Age-related alterations in potentiation in the CA1 region in F344 rats.

F344 rats of various ages (2-3 months, 15-16 months, and 24-25 months) were tested on a spatial memory task. The 15- and 24-month-old rat groups showed impaired acquisition and retention of the memory task, compared to the young animals. Extracellular field potential recordings in the CA1 region were subsequently performed in vitro, using hippocampal slices from both these tested rats and similar but untested F344 young and aged rats. Findings included: a) a positive correlation between baseline dendritic EPSP slope values and retention scores across age groups; b) a more rapid decay of both somatic and dendritic short-term potentiation in aged slices; c) decreased somatic but not dendritic long-term potentiation overall in aged slices, regardless of bath Mg2+ level; and d) decreased paired-pulse facilitation in slices from aged rats bathed in 4.0 mM Mg2+ media compared to young controls. These findings suggest an age-related alteration in both presynaptic and postsynaptic potentiation mechanisms, which may relate to the poor spatial memory acquisition and retention in the aged rats. These age-related differences point to substantial changes in neuronal signal processing capabilities and local circuit function in the hippocampus as a function of aging.

Aging↗
PubMed1994

Effects of estradiol on radial arm maze performance of young and aged rats.

Gonadectomized male and female Sprague-Dawley rats, given estradiol (E2) via sc Silastic capsules that generated proestrus levels of hormones, were tested for spatial memory performance on an 8-arm radial maze. Performance of males, with or without E2, exceeded that of females, with or without E2, for choice accuracy parameters over 20 trials. In addition, males reached criterion earlier than females (6 vs 11 trials). There were no significant effects of E2 on performance of either sex. When a 1-h delay was instituted between the 4th and 5th choices, the performance of males remained better than that of the females, and E2 administration was associated with a small, but significant, improvement in performance of the males but not the females. E2 administration to 25-month-old males also did not affect performance in regular trials, but performance was enhanced in trials with delays of 1-3 h after the 4th choice. These results show that estradiol can influence spatial memory performance and suggest that E2 may be beneficial for age and/or disease-related memory impairments.

Aging↗