Visible Platform Task Research Articles

Effect of Acute Administration of Ethanol Extract of Wild Fig (Ficus thonningii) on Spatial Memory and Learning in CD-1 Mice

Background and Aim: Since there is an increasing demand by people for means of enhancing the neuro-cognitive functions of the brain and the side effects of many neuro-cognitive drugs which have left many persons with irreversible neurological damage. This situation has lead to our investigation of the neuro-cognitive properties (learning and memory) of the plant, Ficus thioningii (wild fig). Methods: 30 Adult Swiss mice weighing between 16 -21g, were divided into 3 groups, 10 mice per group. Before the neurobehavioral parameters were assessed, the LD50, acute toxicological screenings of the plant were determined. Group A being the control, received rat feed with normal saline, group B being the low dose were administered with Ficus thoninngii extract at a dose of 10mg/kg and group C being the high dose were administered with Ficus thoninngii extract at a dose of 20mg/kg, this administration lasted for 14 days. All animals were allowed clean drinking water. Results: The data’s were analyzed and the results showed that on days 1, 2 and 3 of acquisition training mice from low dose and high dose learned equally when compared to the control. In the reversal training, memory was improved in the low dose and high dose treated mice when compared to control at (p<0.05, p<0.01 and p<0.001). During the probe trial, the swim duration in the South-East quadrant was significantly higher for high dose and low dose compared to control (p<0.01 and at p<0.001). However, during the visible platform task, the swim latencies for the low dose and high dose group were also significantly lower compared to control (p<0.001). Conclusion: The results suggest that consumption of Ficus thoninngii extracts enhances learning and memory in mice, thus Ficus thoninngii containing diet may be beneficial in the improvement of learning and memory.

Effects of Aqueous Leaf Extracts of Murraya koenigii on Learning and Memory in Mice

Curry (Muraya koenigii) leaf is an essential leafy spice used widely in cuisine for its distinct flavor and for other medicinal purposes: Analgesic, antidysenteric, antioxidant and in regulating fertility. The Morris water maze was used to study the effects of aqueous extracts of M. koenigii (curry) leaf on learning and memory. Aqueous leaf extracts of M. koenigii (80mg/kg, p.o.) was administered to 7 CD1 strain of mice (18-28 g body weight) while the control group received 0.1 ml/10 kg body weight of distilled water (orally) for 10 days before behavior was assessed. All mice were tested in the Morris water maze for 8 days: At 4 trials per day and 60 seconds per trial. Day 1-3 were for acquisition training, day 4-6 reversal training, day 7, the probe trail and day 8 visible platform task. Results indicate that swim latency were not significantly different between the groups during acquisition and reversal training. The retention quadrant duration was significantly higher for the M. koenigi-treated mice compare to the control (P&lt;0.05). The mice treated with M. koenigi showed a negative weight gain, indicating weight loss (p&lt; 0.05). Therefore the aqueous extracts of M. koenigi improved visuospatial memory in the mice and decreased body weight.

Abstract WP135: CD36 Contributes to Stroke Induced Cognitive Deficits

Introduction: The number of preclinical studies employing long term behavioral testing is increasing. However, long-term behavioral evaluations in genetic animal models is often confounded by their acute injury severity. In addition, these studies have been primarily focused on motor outcomes despite stroke patients also suffer from a wide range of cognitive and psychiatric disturbances. The purpose of study is to investigate recovery via comprehensive behavior assessments in WT and CD36KO mice. Methods: Male and female mice were subjected to right transient MCA occlusion for different durations: 30 for WT and 40 min for CD36KO (N= 13/group) to normalize their injury size. A battery of tests for i) motor (rotarod, open field), ii) anxiety (plus maze, Light dark box), and iii) depression (sucrose preference, forced swim test) were performed before, and 2 weeks and 7 weeks after stroke. Cognitive function is assessed at 9 weeks using a water maze protocol consisting of a training phase, probe trial, and a visible platform relearning task. Results: At baseline KO animals showed reduced rotarod performance and hypoactivity. Infarct sizes were comparable between genotypes. Stroke induced hyperactivity, motor and hedonic deficit and reduced depression like behavior at 2 and 7w in WT mice. CD36 deficiency ameliorated hyperactivity, anhedonia and normalized the depressive behavior. In the water maze training and probe trial, all groups showed similar performance. However among stroke groups CD36 KO mice performed significantly better compared to WT mice at the visible platform task. (Figure) Conclusion: The study demonstrate that CD36 deficiency attenuates stroke-induced hyperactivity, hedonic deficit, reduced depression and relearning deficit. Strategy switching deficit observed in WT stroke animals resemble the cognitive dysexecutive syndrome observed in some stroke patients. Our findings indicate that CD36 contribute to stroke-induced cognitive deficits.

CCK-8 Inhibits Acute Morphine-induced Spatial Reference Memory Impairment in Mice

Administration of morphine may impair learning and memory processes. Cholecystokinin has been reported to be involved in various types of memory, and our previous study found that Cholecystokinin octapeptide attenuates spatial memory impairment in chronic morphine-treated mice. However, the effect of CCK-8 on acute morphine-induced memory impairment is not clear. In this study, effect of acute CCK-8 and morphine on spatial reference memory was evaluated using Morris water maze in KM mice. Acetylcholine (Ach) content was measured using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS). Pre-training with morphine (5, 10 mg/kg, i.p.) significantly impaired spatial reference memory acquisition without disturbing the performance in the visible platform task, while pre-test morphine has no effect on memory retrieval. Pre-training (0.01, 0.1 and 1 μg, i.c.v.) or pre-test (0.1 and 1 μg, i.c.v.) of CCK-8 facilitated spatial reference memory acquisition and retrieval, respectively. CCK-8 (0.1 and 1 μg) significantly attenuated memory loss by pre-training morphine. Furthermore, CCK-8 (1 μg, i.c.v) increased acetylcholine contents of hippocampus in saline or morphine-treated mice. Our study identifies CCK-8 reversed spatial reference memory loss induced by acute morphine, and the mnemonic effect could be related to the facilitation of CCK-8 on memory acquisition and retrieval through accelerating acetylcholine release in hippocampus.

EFFECTS OF LONG-TERM ADMINISTRATION OF COOKED BEANS (Vigna unguiculata) DIET ON LEARNING AND MEMORY IN MICE

Purpose: The neurotransmitter, serotonin has neurobehavioural actions which include mood, memory, learning and sleep. Beans, the stable diet of Nigerians contains serotonin and its precursor, 5-Hydroxytryptophan in significant amounts. It was therefore the aim of this study to find out whether long term consumption of cooked beans (Vigna unguiculata) diet has effects on some neurobehavioural parameters notably; learning and memory, using Swiss white mice as experimental animals.Method: Thirty (30) CD1 mice were randomly assigned into three groups, viz; (10, control, 20 Test) weighing 15-30g were fed normal rodent chow, 50% cooked beans diet (w/w) respectively and serotonin precursor (5-HTP) diet (0.2mg/50g w/w) for thirty days. All the mice had access to clean drinking water ad libitum. Before the neurobehavioural parameters were assessed, the phytochemical analysis of the beans, LD50 of the beans (Vigna unguiculata) and that of the serotonin precursor (5-HTP) were determined. Serotonin concentration was measured in the beans using gas chromatography analysis. Learning and memory, was investigated alongside food and water intake and body weight change. Involvement of serotonin pathway was investigated using the set of mice administered serotonin precursor for comparison with the beans diet fed mice. Mice were tested in the Morris water maze for 8 days: 3 days of acquisition training, 3 days of reversal training, 1 day of single probe trial and 1 day for visible platform task.Results: Learning on days 1, 2 &amp; 3 of acquisition training was improved in the cooked beans and serotonin precursor diet-fed mice when compared to control (p&lt;0.001, respectively). The trend was similar during the reversal training, memory was improved in the beans and serotonin precursor diet-fed mice when compared to control (p&lt;0.001). During the probe trial, the swim duration in the South-East quadrant was significantly higher for cooked beans and serotonin precursor group compared to control (p&lt;0.05). However, during the visible platform task, the swim latencies for the cooked beans and serotonin precursor group was significantly lower compared to control. Our finding therefore suggests that long term consumption of beans diet enhances learning and memory. Conclusion and Recommendation: In conclusion, long term consumption of cooked beans diet enhances learning and memory. If this research can be extrapolated to humans, we recommend that the serotonergic potential of beans may be harnessed in the prevention, treatment and management of behaviour/ mental disorders as this could potentially open up a vista for improved mental health status in populations globally.

Specific downregulation of hippocampal ATF4 reveals a necessary role in synaptic plasticity and memory.

Prior studies suggested that the transcription factor ATF4 negatively regulates synaptic plastic and memory. By contrast, we provide evidence from direct in vitro and in vivo knockdown of ATF4 in rodent hippocampal neurons and from ATF4-null mice that implicate ATF4 as essential for normal synaptic plasticity and memory. In particular, hippocampal ATF4 downregulation produces deficits in long-term spatial memory and behavioral flexibility without affecting associative memory or anxiety-like behavior. ATF4 knockdown or loss also causes profound impairment of both long-term potentiation (LTP) and long-term depression (LTD) as well as decreased glutamatergic function. We conclude that ATF4 is a key regulator of the physiological state necessary for neuronal plasticity and memory.

Harmine treatment enhances short-term memory in old rats: Dissociation of cognition and the ability to perform the procedural requirements of maze testing

Harmine is a naturally occurring monoamine oxidase inhibitor that has recently been shown to selectively inhibit the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A). We investigated the cognitive effects of 1mg (low) Harmine and 5mg (high) Harmine using the delayed-match-to-sample (DMS) asymmetrical 3-choice water maze task to evaluate spatial working and recent memory, and the Morris water maze task (MM) to test spatial reference memory. Animals were also tested on the visible platform task, a water-escape task with the same motor, motivational, and reinforcement components as the other tasks used to evaluate cognition, but differing in its greater simplicity and that the platform was visible above the surface of the water. A subset of the Harmine-high treated animals showed clear motor impairments on all behavioral tasks, and the visible platform task confirmed a lack of competence to perform the procedural components of water maze testing. After excluding animals from the high dose group that could not perform the procedural components of a swim task, it was revealed that both high- and low-dose treatment with Harmine enhanced performance on the latter portion of DMS testing, but had no effect on MM performance. Thus, this study demonstrates the importance of confirming motor and visual competence when studying animal cognition, and verifies the one-day visible platform task as a reliable measure of ability to perform the procedural components necessary for completion of a swim task.

Long-term vision and non-vision dominant behavioral deficits in the 2-VO rats are accompanied by time and regional glial activation in the white matter.

The permanent occlusion of common carotid arteries (2-VO) in rats has been shown to induce progressive and long-lasting deficits in cognitive performance, however, whether these aberrant behaviors are attributed to visual dysfunction or cognitive impairment and what are the underlying mechanisms, remain controversial. In the present study, vision dominant (Morris water maze) and non-vision dominant (voice-cued fear conditioning) behavioral tests were assigned to comprehensively evaluate the influence of 2-VO lesion on cognitive behaviors. In the Morris water maze test, escape latencies of 2-VO rats were markedly increased in both hidden and unfixed visible platform tasks, which were accompanied by severe retinal damage. In the voice-cued fear conditioning test, significant reduction in the percentage of freezing behavior was observed at 60 days after 2-VO lesion. Chronic lesion by 2-VO failed to cause noticeable changes in the grey matter, as indicated by intact hippocampal and prefrontal cortical structures, sustained synaptic protein levels and glial cell numbers. In contrast, aberrant arrangement of myelinated axons was observed in the optic tract, but not in the corpus callosum and inner capsule of 2-VO rats. Concurrently, marked astrocyte proliferation and microglia activation in the optic tract occurred at 3 days after 2-VO lesion, and continued for up to 60 days. Differently, robust glial activation was observed in the corpus callosum at 3 days after 2-VO surgery, and then gradually returned to the baseline level at 14 and 60 days. Our study reported for the first time about the effect of 2-VO on the long-term cognitive impairment in the non-vision dominant fear conditioning test, which may be more applicable than the Morris water maze test for assessing 2-VO associated cognitive function. The time and region specific glial activation in the white matter may relate to retinal impairment, even behavioral deficits, in the setting of chronic cerebral hypoperfusion.

Binge inhalation of toluene vapor produces dissociable motor and cognitive dysfunction in water maze tasks

Binge inhalation of toluene, a psychoactive chemical found in many household and industrial products, leads acutely to intoxication with comorbid impairments in motor function and cognitive abilities that appear to recover quickly. Recent evidence, however, indicates that the administration of toluene results in marked changes in neurons of the medial prefrontal cortex that persist for relatively longer periods compared with other brain regions. To elucidate the potential toluene-induced (∼5000 ppm) cognitive dysfunctions that continue following the recovery of locomotor abilities, rats were entered into a series of water maze tasks. Following acute toluene intoxication, rats were initially severely impaired in their swimming ability and in their ability to learn and perform a visible platform task. After about 20 min, swimming behavior mostly returned to normal, although cognitive impairments were still evident. Whereas rats with extensive toluene-free training in the maze were able to show normal spatial recall following toluene intoxication, the same acute toluene exposure severely impaired reversal learning, with the rats showing a marked perseveration for the previously learned platform location. Our results indicate that toluene inhalation results in specific cognitive dysfunctions that outlast major impairments in motor abilities, which may be related to impairments in medial prefrontal cortex activity.

Agmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosis

Neuroinflammation is associated with a number of neurodegenerative diseases. It is known that lipopolysaccharide (LPS) treatment induces neuroinflammation and memory deterioration. Agmatine, the metabolite of arginine by arginine decarboxylase, is suggested to be a neuroprotective agent. The aim of this study was to explore if agmatine can prevent LPS-induced spatial memory impairment and hippocampal apoptosis. Adult male Wistar rats (200-250 g) were trained in water maze for 4 days (3 days in hidden platform and the last day in visible platform task). Saline, LPS (250 microg/kg/ip) or (and) agmatine (5 or 10 mg/kg) were administered 4h before every training session. LPS treatment impaired water maze place learning while agmatine co-administration prevented it. Also western blot studies revealed that LPS induces hippocampal caspase-3 activation while agmatine treatment prevented it.

Effect of methamphetamine exposure and cross-fostering on cognitive function in adult male rats

The aim of our study was to examine the effect of prenatal methamphetamine (MA) exposure and cross-fostering on cognitive functions of adult male rats tested in Morris water maze (MWM). Rat mothers were exposed daily to injection of MA (5mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Females without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised 4 pups of her own and 8 pups from the mothers with the other two treatments. Four types of tests were used: (1) Place navigation test (Learning), (2) Probe test (Probe), (3) Retention memory test (Memory) and (4) Visible platform task. Our results demonstrate that the prenatal exposure to MA does not impact learning and memory, while postnatal exposure to MA shows impairments in cognition. In the test of learning, all animals fostered to MA-treated dams had longer latencies, bigger search error and used lower spatial strategies than the animals fostered to control or saline-treated mother, regardless of prenatal exposure. Regardless of postnatal exposure, the animals prenatally exposed to saline swam faster in all the tests than the animals prenatally exposed to MA and controls, respectively. This study indicates that postnatal but not prenatal exposure to MA affects learning in adult male rats. However, it is still not clear whether these impairments are due to a direct effect of MA on neuronal structure or due to an indirect effect of MA mediated by impaired maternal care.

Effect of acetaminophen, a cyclooxygenase inhibitor, on Morris water maze task performance in mice

Although the mechanism of action of acetaminophen (AAP) is not fully understood, some studies suggest that AAP and phenacetin (PHE) are selective cyclooxygenase (COX)-3 inhibitors. To examine the participation of COX-3 in memory formation, water maze performance was studied in mice treated with AAP, PHE or other COX inhibitors. Mice received intraperitoneal injections of drugs immediately after each training session. Administration of high-dose AAP [302.3 mg/kg (IC50 for COX-2)] or PHE [179.2 mg/kg (IC50 for COX-2)] and of non-specific (indomethacin: 20 mg/kg) or specific COX-2 (NS-398: 10 mg/kg) inhibitor impaired the performance in hidden platform (HP) not visible platform (VP) tasks, whereas low-dose (15.1 mg/kg) AAP facilitated performance in HP and VP tasks. The facilitation of performance by low-dose AAP was reversed by co-administration with a 5-HT(1/2) receptor antagonist (methysergide: 0.47 mg/kg). The middle-dose [69.5 mg/kg (IC50 for COX-3)] of AAP, the PHE [17.9 mg/kg (IC50 for COX-3)] and a specific COX-1 inhibitor (piroxicam: 10-20 mg/kg) did not influence performance in either task. These results suggest that the memory impairment by high-dose AAP and PHE and facilitation of performance by low-dose AAP could involve endogenous COX-2 and serotonergic neuronal activity, but not COX-3, respectively.

Combined but not Individual Administration of β-Adrenergic and Serotonergic Antagonists Impairs Water Maze Acquisition in the Rat

This study examined the effects of serotonergic depletion and beta-adrenergic antagonism on performance in both visible platform and hidden platform versions of the water maze task. Male Long-Evans rats received systemic injections of p-chlorophenylalanine (500 mg/kg x 2) to deplete serotonin, or propranolol (20 or 40 mg/kg) to antagonize beta-adrenergic receptors. Some rats received treatments in combination. To separate strategies learning from spatial learning, half of the rats underwent Morris' water maze strategies pretraining before drug administration and spatial training. Individual depletion of serotonin or antagonism of beta-adrenergic receptors caused few or no impairments in either naive or pretrained rats in either version of the task. In contrast, combined depletion of serotonin and antagonism of beta-adrenergic receptors impaired naive rats in the visible platform task and impaired both naive and strategies-pretrained rats in the hidden platform task, and also caused sensorimotor impairments. This is the first finding of a 'global' water maze task/sensorimotor impairment with combined administration of two agents that, at the high doses that were given individually, produced few or no impairments. The data imply that (1) serotonergic and beta-adrenergic systems may interact in a manner that is important for adaptive behavior; (2) impairments in these systems found in Alzheimer patients may be important for their cognitive and behavioral impairments; and (3) the approach used here can model aspects of the cognitive and behavioral impairments in Alzheimer disease.

GAP-43 gene expression regulates information storage

Previous reports have shown that overexpression of the growth- and plasticity-associated protein GAP-43 improves memory. However, the relation between the levels of this protein to memory enhancement remains unknown. Here, we studied this issue in transgenic mice (G-Phos) overexpressing native, chick GAP-43. These G-Phos mice could be divided at the behavioral level into "spatial bright" and "spatial dull" groups based on their performance on two hidden platform water maze tasks. G-Phos dull mice showed both acquisition and retention deficits on the fixed hidden platform task, but were able to learn a visible platform task. G-Phos bright mice showed memory enhancement relative to wild type on the more difficult movable hidden platform spatial memory task. In the hippocampus, the G-Phos dull group showed a 50% greater transgenic GAP-43 protein level and a twofold elevated transgenic GAP-43 mRNA level than that measured in the G-Phos bright group. Unexpectedly, the dull group also showed an 80% reduction in hippocampal Tau1 staining. The high levels of GAP-43 seen here leading to memory impairment find its histochemical and behavioral parallel in the observation of Rekart et al. (Neuroscience 126: 579-584) who described elevated levels of GAP-43 protein in the hippocampus of Alzheimer's patients. The present data suggest that moderate overexpression of a phosphorylatable plasticity-related protein can enhance memory, while excessive overexpression may produce a "neuroplasticity burden" leading to degenerative and hypertrophic events culminating in memory dysfunction.

Ethological analysis of the senescence-accelerated P/8 mouse

Behaviour of senescence-accelerated (P/8) and resistant (R/1) mice was assessed using an ethological approach in a longitudinal study for exploratory and anxiety related behaviours (home cage activity, open field, elevated plus-maze and new object tests), cognitive abilities (step-down and step-through passive avoidance and water maze tests) and visual acuity (visible cliff test). Overall, P/8 mice showed higher activity induced by new environmental stimuli, higher anxiety and lower novelty seeking behaviour in the new object test than R/1 mice. P/8 mice showed an impaired performance as compared to R/1 mice in two passive avoidance tasks. Behavioural alterations of P/8 mice were already apparent at the age of 10–12 weeks. Factor analyses indicated that the impairment of P/8 mice in passive avoidance tasks relates to their altered exploratory and anxiety-related behaviour rather than to cognitive impairments. In the water maze, both strains performed badly in the visible platform task, suggesting poor visual abilities in both strains as supported by the visible cliff test. We conclude that, for a better interpretation of cognitive abilities of P/8 mice, tests not based on novelty-induced behaviour, visual acuity and good motor skills should be used. Finally, we question whether P/8 mice could be a model of some forms of neuropsychiatric disorders resulting from developmental abnormalities rather than ageing.

The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task

In this study, the effects on memory of intraperitoneal post-training administration of cyclic nucleotide phosphodiesterase (PDE) inhibitors, DC-TA 46 and rolipram, were tested using a visible/hidden-platform water maze task. The effects of these compounds on cyclic nucleotide levels in the hippocampal formation (HF) and striatum (CP) were also assessed, by enzymatic immunoassay (EIA). The results obtained from rats trained in the visible-platform task were not significantly different from controls. On the contrary, the animals trained in the hidden-platform water maze task showed a memory impairment, when injected with DC-TA 46 at maximal dose of 20 mg/kg and with rolipram at 3 and 30 mg/kg doses. The effects of these drugs on cyclic nucleotide levels in HF and CP were observed at 30 min and at 24 h after drug administration. Thirty minutes after drug injection, we observed an increase of cAMP level, both in HF and in CP. Twenty-four hours after the retention test, we observed that in CP the cAMP intracellular level remained high, while in the HF at effective doses both inhibitors induced cAMP PDE activity, determining a decrease of cyclic nucleotide. Semi-quantitative RT–PCR analysis, together with Western blot immunodetection, showed a mRNA and protein induction of PDE4D PDE isoforms, that may account for the increase of PDE activity observed. Our data suggest that, despite cyclic nucleotide increase at 30 min, the fundamental event causing memory impairment, came from the subsequent long time decrease of cAMP levels, due to the post-translational PDE4D induction.

Dysexecutive syndrome after mild cerebral ischemia? Mice learn normally but have deficits in strategy switching.

We determined long-term functional outcome in a well-characterized mouse model of mild focal cerebral ischemia. We subjected 129/SV mice to sham operation or 30 minutes of left middle cerebral artery occlusion (MCAo) followed by reperfusion (89% survival rate). Six weeks later, animals were tested for neurological deficits, motor coordination on an accelerating Rota-rod apparatus, and spatial navigation in a water maze task. Brain lesion size was determined on NeuN-immunostained coronal brain sections by computer-assisted volumetry. Mice had mild but distinct neurological deficits and no deficits in Rota-rod coordination or swimming speed 6 weeks after MCAo. Moreover, mice had normal spatial learning abilities in the place task. However, stroke mice had deficits in the probe trial and visible platform task, which correlated with striatal lesion size determined on NeuN-immunostained sections. After mild ischemia, mice recover with mild neurological deficits and normal motor coordination. Stroke mice have no obvious deficits in spatial learning in the Morris water maze but display distinct deficits related to strategy switching and relearning.

Selective loss of hilar neurons and impairment of initial learning in rats after repeated administration of electroconvulsive shock seizures.

Prolonged seizures induced by neurotoxins or intracranial electrical stimulation provoke death of hippocampal neurons, which results in conspicuous learning and memory deficits. We examined whether repeated brief seizures elicited by electroconvulsive shock (ECS) can also deteriorate hippocampal structure and function. Adult Wistar rats were administered six ECS seizures, the first five of which were 24 h apart, whilst the last two were spaced by a 2-h interval. Following a 2-month recovery period, the cognitive status of the animals was assessed using the water maze task. ECS-treated animals were incapable of learning the constant platform position version of this task during the first 4 days of training, but performed similarly to control rats throughout the rest of the acquisition period, on the probe trial, and on the variable platform position and visible platform tasks. The results of the morphological analysis showed that the total number of hippocampal pyramidal neurons and dentate gyrus granule cells were similar in control and ECS-treated rats. However, ECS treatment caused loss of approximately 17% of cells in the hilus of the dentate gyrus, which was accompanied by significant mossy fiber sprouting into the dentate inner molecular layer. In addition, we found that the ECS-induced decrease in the total number of hilar cells was not due to loss of inhibitory interneurons immunoreactive to somatostatin. These findings support the view that ECS-induced seizures can produce a number of morphological and functional changes in the rat hippocampal formation, which qualitatively resemble those previously described in other seizure models.

Detailed behavioral analysis reveals both task strategies and spatial memory impairments in rats given bilateral middle cerebral artery stroke

Middle cerebral artery occlusion (MCAO) impairs performance in the water maze task by rats. The purpose was to evaluate the effect of bilateral MCAO in naive and strategies-pretrained rats using a detailed behavioral analysis to further develop a water maze model of stroke. Rats were trained in either a simple swim-to-visible platform task or in a conventional spatial version with a hidden platform in the pool. In the visible platform task naive stroked rats were impaired because of a marked tendency to swim thigmotaxically on most trials. For the spatial learning experiment, some rats received Morris’ water maze strategies pretraining prior to MCAO and subsequent spatial training to familiarize them with the general behavioral strategies required in the task. In the spatial learning task naive stroked rats had both strategies and spatial learning impairments but pretrained stroked rats were indistinguishable from sham controls on all behavioral measures. All stroked rats had comparable bilateral brain damage measured using a computerized volumetric measuring technique. These results indicate that in naive rats bilateral MCAO causes behavioral strategies impairments in the visible and hidden platform versions of the water maze as well as specific spatial learning impairments in the hidden platform version. The results also indicate that behavioral strategies pretraining allows stroked rats to acquire and remember sufficient strategies skills and spatial information to perform as well as sham controls during subsequent spatial training. These techniques appear to be capable of quantifying the effects of potentially protective treatments for stroke.

Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months

Behavioral characterization of Alzheimer's disease (AD) transgenic models over multiple time points during aging has been largely inadequate, usually being limited to one or two cognitive-based tasks. In this context, the present study utilized a comprehensive 6-week behavioral battery to characterize sensorimotor and cognitive performance of Tg2576 AD transgenic (Tg +) mice and nontransgenic (Tg −) controls aged 3, 9, 14, and 19 months. Compared collectively to Tg − mice over all four time points, Tg + mice were impaired in Y-maze spontaneous alternation, visible platform recognition, and several sensorimotor tasks; Tg + mice also showed an overall increase in activity measures. The deficits in visible platform became evident by 9 months of age, while those in sensorimotor tasks became clearly manifest by 14 months. Although the behavioral impairments exhibited by Tg + mice were usually progressive through 19 months, Tg − animals also showed similar progressive decline in the same behavioral measures; thus, no task revealed a progressive behavioral decline exclusive to Tg + mice. Moreover, although the 6-week behavioral battery included six cognitively based tasks (i.e., Y-maze, visible platform, Morris water maze, circular platform, passive avoidance, and active avoidance), behavioral analysis through 19 months revealed Tg + mice to be impaired in only the Y-maze and visible platform tasks. Consequently, Tg2576 mice do not exhibit widespread, profound cognitive impairment, even into old age. This may reflect their predominant C57BL/6 background and an apparent inability of the mutant transgene to profoundly alter performance therein.