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At least 1,063 records · Page 59Linked to original sources
PubMed2002

Behavioural changes related to olfactory mucosal metaplasia and bulbar glial fibrillary acidic protein (GFAP) induction in methylsulphonyl-dichlorobenzene-treated mice.

Methylsulphonyl-2,6-dichlorobenzene [2,6-(diCl-MeSO(2)-B)], and its 2,5-chlorinated isomer [2,5-(diCl-MeSO(2)-B)] bind firmly in the olfactory mucosa of mice. Both isomers are also selectively localised in the olfactory bulb. Persistent olfactory mucosal metaplasia is induced by 2,6-(diCl-MeSO(2)-B) whereas 2,5-(diCl-MeSO(2)-B) has no effects. Furthermore, a strong induction of glial fibrillary acidic protein (GFAP) restricted to the olfactory bulb has been reported in 2,6-(diCl-MeSO(2)-B)-treated mice. To explore whether these lesions give rise to early or long-lasting changes in behaviour, spontaneous motor activity and radial arm maze (RAM) learning were examined at 1, 2, 4 and 12 weeks following an intraperitoneal injection of a single low (32 mg/kg) or high (65 mg/kg) dose of 2,6-(diCl-MeSO(2)-B). 2,5-(DiCl-MeSO(2)-B) (65 mg/kg) was used as a negative control. Hyperactivity was observed in all treatment groups while deficits in the RAM performance was only seen in the 2,6-(diCl-MeSO(2)-B)-treated groups. Alterations in motor activity and impaired performance in the RAM-test induced by 2,6-(diCl-MeSO(2)-B) persisted up to 2 weeks in the low-dose group and 12 weeks in the high-dose group. The low-dose group consistently showed a less pronounced effect than the high-dose group. The 2,5-(diCl-MeSO(2)-B)-induced changes in motor activity declined rapidly and did not remain after 2 weeks. As determined by immunohistochemistry, 2,6-(diCl-MeSO(2)-B)-induced GFAP immunoreactivity was mainly confined to the glomerular layer of the olfactory bulb. We propose that the behavioural deficits caused by 2,6-(diCl-MeSO(2)-B) result from a primary loss of sensory neurons in the olfactory mucosa with consequent astrocyte proliferation in the glomerular layer of the olfactory bulb. A targeted uptake of metabolites into the olfactory bulb could also contribute to the GFAP induction and/or behaviour response.

Animals↗
PubMed1998

50 Hz magnetic field effects on the performance of a spatial learning task by mice.

Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 microT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 microT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5 microT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible.

Analysis of Variance↗
PubMed2004

Egocentric conditional associative learning: effects of restricted lesions to the hippocampo-mammillo-thalamic pathway.

Rats with lesions of the hippocampus, the mammillary region, the anterior thalamic nuclei, and normal control animals were trained on a conditional associative learning task in which they had to learn to make one of two motor responses (i.e., turn left or right), depending on which one of two visual cues was presented. Damage to the hippocampus severely impaired performance of this task. By contrast, rats with lesions of the mammillary region or the anterior thalamic nuclei were able to acquire the task at a rate comparable to that of the normal animals. These findings demonstrate that hippocampal lesions impair the ability to form arbitrary associations between visual cues and kinesthetic responses (body turns) and, furthermore, suggest that the hippocampus does not rely on input from its major subcortical targets for learning such visual-kinesthetic associations.

Animals↗
PubMed2006

Self-handicapping prior to academic-oriented tasks in children with attention deficit/hyperactivity disorder (ADHD): medication effects and comparisons with controls.

Examined self-handicapping prior to academic-oriented tasks in children with and without ADHD and examined whether stimulant medication influenced self-handicapping. Participants were 61 children ages 6 to 13, including 22 children with ADHD tested after taking a placebo, 21 children with ADHD tested after taking stimulant medication, and 18 non-ADHD controls. Participants completed three measures of self handicapping and also completed self-evaluations of their performance. Results showed greater self handicapping and more positive self-evaluations in children with ADHD than in controls regardless of medication condition. Findings suggest children with ADHD may use self handicapping to ameliorate the effects of experiencing high rates of academic failure.

Adolescent↗
PubMed1996

Differential effects of anticholinergic drugs on paired discrimination performance.

Working and reference memory processes were simultaneously evaluated during the performance of a paired discrimination (PD) task in which visual and spatial discrimination trials were combined within the same session. Atropine (1 and 5 mg/kg), scopolamine (0.02-0.20 mg/kg), benactyzine (1-4 mg/kg), trihexyphenidyl (1-10 mg/kg), and aprophen (5-20 mg/kg) were all found to increase the number of errors performed by overtrained rats during the spatial but not during the visual trials. Although all the anticholinergic drugs tested induced specific working memory impairment at low doses, they differentially affected other, simultaneously recorded, behavioral parameters. Thus, while atropine affected most of the recorded parameters, aprophen induced only a mild effect. Benactyzine was found to have the most specific effect on working memory, with only minimal side effects, a combination that supports its use as the preferred psychopharmacological model of working memory impairment.

Animals↗
PubMed2004

Sequential control of navigation by locale and taxon cues in the Morris water task.

The neurobehavioral dissociation between place navigation and cued navigation has been central to contemporary thinking regarding the psychological processes involved in spatial behavior. In cases where locale (place) cues and taxon cues (e.g., beacons) are present it has been suggested that navigation may be controlled by either stimulus type in isolation, or, alternatively, by both simultaneously. In this report we provide evidence that place cues and beacons sequentially control navigation during a single trip to a visible goal. Rats were trained to navigate to a visible escape platform in a circular swimming pool surrounded by numerous visual cues and the kinematics and accuracy of the trajectories to the platform were analyzed. Shortly after initiating a trajectory to the visible platform, animals routinely engaged in stimulus sampling behaviors (e.g., horizontal head scans) which were consistently associated with changes in accuracy (heading error) and swim velocity. Subsequently, animals swam quickly and accurately to the visible platform suggesting that the sampling behaviors correspond to a shift in exteroceptive stimulus control. Consistent with this idea, removal or relocation of the platform disrupted navigation following the stimulus sampling behaviors, whereas the initial trajectory was unaffected. In contrast, changes in the distal cue constellation selectively disrupted the initial trajectory. The results showing that navigation to a visible goal is controlled sequentially by locale and taxon cues are discussed in relation to contemporary theories of navigation.

Animals↗
PubMed2004

Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus non-spatial behavior.

In the face of contradictory findings on the role of visual cortex contributions to spatial behavior, the present study evaluated the ability of rats with primary visual cortex (Area 17) lesions to learn spatial problems in a swimming pool. Because the solution to any spatial learning problem consists of acquiring at least two primary elements of a task, task procedures and spatial learning, the study, in addition to assessing spatial ability on a place task, used two training/testing methods to identify the nature of the spatial impairment associated with visual cortex lesions. Non-spatial training consisted of learning to find a platform in the dark and spatial training consisted of a series of matching-to-place problems. The results confirmed that although rats with visual cortex lesions were impaired on place learning, the deficit was partially ameliorated by non-spatial training given following the lesion, and completely ameliorated by non-spatial training given before the lesion. Nevertheless, all visual cortex groups failed to show a quadrant preference on a probe trial and displayed a profound impairment in matching-to-place learning. This definitive demonstration that appropriate testing methods can reveal a failure in spatial behavior following visual cortex lesions is consistent with the idea that primary visual cortex is required in spatial navigation.

Analysis of Variance↗
PubMed2005

Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit.

The cytosolic brain-type creatine kinase (BCK) isoform and the mitochondrial ubiquitous creatine kinase (UbCKmit) isoform are both important for the maintenance and distribution of cellular energy in neurons and astrocytes. Previously, we reported that mice deficient for BCK or UbCKmit each showed a surprisingly mild phenotype, probably due to reciprocal functional compensation by the remaining creatine kinase. This study shows that adult male mice lacking both creatine kinase isoforms (CK--/-- double knockout mice) have a reduced body weight, and demonstrate a severely impaired spatial learning in both a dry and a wet maze, lower nestbuilding activity and diminished acoustic startle reflex responses when compared to age-matched male wildtype mice with the same genetic background. In contrast, their visual and motor functions, exploration behaviour, prepulse inhibition and anxiety-related responses were not changed, suggesting no global deficit in sensorimotor function, hearing or motivation. Morphological analysis of CK--/-- double knockout brains revealed a reduction of approximately 7% in wet brain weight and hippocampal size, a approximately 15% smaller regio-inferior and relatively larger supra-pyramidal, and intra-infra-pyramidal mossy fiber areas. These results suggest that lack of both brain specific creatine kinase isoforms renders the synaptic circuitry in adult brain less efficient in coping with sensory or cognitive activity related challenges.

Acoustic Stimulation↗
PubMed2005

Mice deficient in microtubule-associated protein MAP1B show a distinct behavioral phenotype and altered retina function.

We investigated mice deficient for the microtubule-associated protein MAP1B, a cytoskeletal element highly expressed in the developing nervous system, for altered performance in behavior, learning, and memory. Using the multiple T-maze, the open field and the Morris water maze we found that mice homozygous for a deletion of the MAP1B gene demonstrate impaired locomotor activity most likely correlated to a lack of physical endurance in general. In contrast, there were no significant differences in cognitive function and memory retention. In addition, we performed electroretinography and observed a reduction of the a-wave amplitude in response to single flash, white light stimulation. Taken together, these data provide further evidence for an important role of MAP1B in synaptic neurotransmission.

Animals↗
PubMed2006

Mild forced treadmill exercise enhances spatial learning in the aged rat.

This study addresses whether or not mild, forced treadmill exercise improves learning and increases neurotrophin levels in the basal forebrain (BF). Neurotrophin deficits in the BF have been implicated in Alzheimer's disease, and physical exercise increases neurotrophins. Aged rats exercised for 7 weeks found the hidden platform faster than controls (F(1, 10)=14.6, p<0.05), and swam shorter pathlengths (F(1, 10)=12.6, p<0.05), with no difference in swim speed. Neurotrophins did not differ.

Aging↗
PubMed2006

Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis.

Evidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Copper treatment alone showed no significant learning and memory impairments in behavioral tasks. However, copper-induced neurotoxicity was significantly increased in mice given elevated-cholesterol diet. Trace amounts of copper decreased the activity of SOD and increased the level of malondialdehyde (MDA) in the brain of cholesterol-fed mouse. Copper also caused an increase in amyloid precursor protein (APP) mRNA level and the activation of caspase-3 in the brain of cholesterol-fed mice. The apoptosis-induced nuclear DNA fragmentation was detected in the brain of those mice by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling staining. These findings suggest that trace amounts of copper induce neurotoxicity in cholesterol-fed mice through apoptosis caused by oxidative stress.

Amyloid beta-Protein Precursor↗
PubMed2006

Effects of gonadectomy on performance in operant tasks measuring prefrontal cortical function in adult male rats.

Previous studies have shown that gonadectomy in adult male rats influences the acquisition and performance of spatial and other working memory tasks that depend in part on the medial prefrontal cortex and its dopamine innervation. Stimulated by previous findings that gonadectomy alters dopamine axon density in not only medial but several other prefrontal fields, the present studies asked whether gonadectomy might also broadly impact dopamine-dependent prefrontal functions, and whether these effects bore any relation to hormone modulation of mesoprefrontal dopamine afferents. Specifically, control, gonadectomized, and gonadectomized rats given estradiol or testosterone propionate were tested on a series of operant tasks that together measured medial prefrontal functions of spatial working memory, impulsivity and extradimensional set shifting and orbital prefrontal functions of reversal learning/perseveration and motivation. Afterwards, animals were sacrificed, their bulbospongiosus muscles were removed and weighed, their brains were processed for immunocytochemistry for the dopamine-synthesizing enzyme tyrosine hydroxylase, and axon densities were measured in orbital and medial prefrontal fields. Statistical evaluations of group effects on behavior and regression analyses comparing individual performance with muscle weights and axon density measures revealed androgen-reversible effects of gonadectomy on acquisition of spatial working memory and extradimensional set shifting that were correlated with bulbospongiosus weight and medial prefrontal dopamine axon density, estrogen-sensitive influences of gonadectomy on motivation and response withholding that were correlated with bulbospongiosus weight but not with dopamine innervation, and still other prefrontal functions, i.e., impulsivity, reversal learning, that were insensitive to gonadectomy and unrelated to gonadectomy-induced changes in muscle weight or prefrontal dopamine innervation.

Afferent Pathways↗
PubMed1997

3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner.

The alpha7 nicotinic receptor agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB; GTS-21) was investigated for its ability to: (1) activate a variety of nicotinic receptor subtypes in Xenopus oocytes; (2) improve passive avoidance and spatial Morris water task performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and (3) elevate high-affinity [3H]acetylcholine (ACh) and high-affinity alpha-[125I]bungarotoxin binding in rat neocortex following 2 weeks of daily injections. DMXB (100 microM) activated alpha7 homo-oligomeric receptors, without significant activity at alpha2-, alpha3- and alpha4-containing subtypes. Mecamylamine blocked rat alpha7 receptors weakly if co-administered with agonist, but much more potently when pre-applied. Bilateral ibotenic acid lesions of the nucleus basalis interfered with passive avoidance and spatial memory-related behaviors. DMXB (0.5 mg/kg, i.p.) improved passive avoidance behavior in lesioned animals in a mecamylamine-sensitive manner. DMXB (0.5 mg/kg 15 min before each session) also improved performance in the training and probe components of the Morris water task. DMXB-induced improvement in the probe component but not the training phase was mecamylamine-sensitive. [3H]ACh binding was elevated after 14 days of daily i.p. injections with 0.2 mg/kg nicotine but not after 1 mg/kg DMXB. Neither drug elevated high-affinity alpha-[125I]bungarorotoxin binding over this interval.

Animals↗
PubMed1997

Essential fatty acid preparation improves biochemical and cognitive functions in experimental allergic encephalomyelitis rats.

This study examined the possible effects of a novel mixture of fatty acids, SR-3 (a specific ratio of alpha-linolenic acids), on brain biochemistry and on learning deficits induced by injection of an agent that induces experimental allergic encephalomyelitis. Treatment with SR-3 caused a decrease in myelin and changes in the fatty acid profile of brain synaptosomes, and a learning deficit. Eighteen days of treatment with SR-3 reversed the biochemical and learning deficit significantly, but did not restore them to normal levels. We propose that, most probably, the main action of SR-3 is the modulation of the cholesterol level, which in turn causes the modulation of the fatty acid profile and enhances learning by allowing improved neuronal communication.

Analysis of Variance↗
PubMedDate not supplied

Place DMTS water-escape with direct placement or response information runs.

A two-choice, spatial delayed matching-to-sample (DMTS) water-escape task has proved to be a valuable of assay of trial-dependent memory. The task involves giving rats trials consisting of a forced-choice information run and a free-choice test run that are separated by a 5-m retention interval. Two experiments were conducted to determine the importance of making a complete response (R), partial response (P), or no response (NR; direct placement on escape platform) during the information "run" on acquisition and the subsequent performance of the task. Most of the naive, male, Sprague-Dawley rats were capable of attaining a 90% correct choice criterion when trained with P or NR information runs, but rats trained with R information runs required fewer trials to attain criterion and had shorter escape latencies during the criterion trials. Rats in all three groups showed significant retention at retention intervals as long as 1 h. Rats overtrained on the task with R information runs were subsequently able to perform the task at above chance level, regardless of the type information run given on the trial, but performed more accurately on trials where they made P or R information runs. Thus, rats use and perform better on place DMTS when allocentric environmental and egocentric response-associated cues are both available.

Animals↗
PubMed2002

Relative contribution of allothetic and idiothetic navigation to place avoidance on stable and rotating arenas in darkness.

In the absence of useful visual or other exteroceptive cues, rats can orient in their environment using idiothetic navigation, the process in which the information generated during self-motion is integrated to yield a homing vector leading the animal back to a point of departure. If perceivable exteroceptive cues in the visited environment are available, their spatial relationship is integrated with idiothetic information and stored in a cognitive map of the environment. Our previous experiments demonstrated that place navigation in rats is severely impaired after devaluation of the intramaze substratal information by shuffling, i.e. by its random displacement relative to the already traversed track. Several interpretative difficulties of the previous study have been eliminated in the present study by the use of an advanced version of the shuffling apparatus. The results show that shuffling-induced impairment of substratal idiothesis depends on the salience of intramaze cues, that on a stable featureless arena, idiothesis can be updated by non-visual allothetic cues, and that shuffling exposing the animal to sudden accelerations and decelerations interferes with idiothetic navigation by the inherent conflict between substratal and inertial idiothesis. It is concluded that pure substratal idiothesis not updated by extramaze and intramaze cues cannot provide reliable navigation over distances longer than 5 m.

Animals↗
PubMed1997

Development of vicarious trial-and-error behavior in odor discrimination learning in the rat: relation to hippocampal function?

Previous work from our laboratory has suggested that hippocampal electrolytic lesions result in a deficit in simultaneous, black-white discrimination learning and reduce the frequency of vicarious trial-and-error (VTE) at a choice-point. VTE is a term Tolman used to describe the rat's conflict-like behavior, moving its head from one stimulus to the other at a choice point, and has been proposed as a major nonspatial feature of hippocampal function in both visual and olfactory discrimination learning. Simultaneous odor discrimination and VTE behavior were examined at three different ages. The results were that 16-day-old pups made fewer VTEs and learned much more slowly than 30- and 60-day-olds, a finding in accord with levels of hippocampal maturity in the rat.

Aging↗