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PubMed1981

The effect of early visual experience on spatial maze learning in rats.

In the 1st of 2 experiments on spatial ability, groups of sighted and blind, light-reared (LR) and dark-reared (DR) rats were tested on a series of (Hebb-Williams) maze problems and their reversals under appetitive and aversive reinforcement conditions. Significant effects due to early rearing conditions, vision at time of testing, and problem were found. Dark-reared rats learned the problems whose solution depended on nonvisual cues more slowly than LR animals. Blindness at time of testing had a significantly adverse effect on the performance of LR and DR rats on all problems, but a significantly greater effect in the DR animals. In a 2nd experiment DR rats were also found to perform less effectively than LR rats on a 17-arm radial maze throughout a 36-day period during which variations in the task were introduced. The results reveal the impact of early visual experience on the development of the ability to acquire spatial concepts.

Animals↗
PubMed1984

Differential rearing experience, gender, and radial maze performance.

Since both differential rearing and gender have been known to affect maze abilities, the present study examines the performance of male and female hooded rats raised from weaning in either a complex environment (EC) or isolated environment (IC) on the 17-arm radial maze. In two separate replications, EC rats learned the maze more quickly and accurately than IC rats, as assessed by total errors, the number of correct choices to the first error, and the number correct in the first 17 choices. However, EC rats were more likely than IC rats to employ an adjacent-arm strategy which may have contributed to their superior performance. There were no gender differences or environment by gender interaction effects on any measure of accuracy or adjacent arm strategy in either replication. It appears that the performance of both male and female rats on the 17-arm radial maze is similarly influenced by the rearing environment.

Animals↗
PubMed2004

Determining the hemispheric dominance of spatial attention: a comparison between fTCD and fMRI.

Human brain mapping allows the systematic assessment of interindividual differences in functional brain anatomy. Functional transcranial Doppler sonography (fTCD) is an imaging tool that allows for fast and mobile assessment of hemispheric lateralization of task-related brain activation. It is ideal to screen large cohorts of subjects. The goal of the present study was to investigate whether fTCD and functional magnetic resonance imaging (fMRI) determine hemispheric lateralization of brain activation related to visuospatial attention concordantly. Used together, fMRI and fTCD may then open up a wide range of potential applications in neuroscience. Fifteen subjects were examined both with fTCD and fMRI while they judged accuracy of line bisections (Landmark task). For fTCD, the maximal mean difference in stimulus-related relative cerebral blood flow velocity changes in the left and right middle cerebral arteries was assessed as the lateralization index LI(fTCD). For fMRI, two approaches were used to determine hemispheric dominance. First, we measured brain activity as the extent of the activated region, i.e., the number of activated voxels above a statistical threshold. Second, we calculated the magnitude of the fMRI signal change between the activation and the control task within a region of interest. Results of fTCD and fMRI were concordant in every single case. Therefore, scanning large cohorts with fTCD for hemispheric dominance during Landmark task will provide results consistent with fMRI. FMRI can then be used for in depth assessment of the specific patterns of activation.

Adult↗
PubMed2005

Place-related neural responses in the monkey hippocampal formation in a virtual space.

Place cells in the rodent hippocampal formation (HF) are suggested to be the neural substrate for a spatial cognitive map. This specific spatial property of the place cells are regulated by both allothetic cues (i.e., intramaze local and distal cues) as well as idiothetic sensory inputs; the context signaled by the distal cues allows local and idiothetic cues to be employed for spatial tuning within the maze. To investigate the effects of distal cues on place-related activity of primate HF neurons, 228 neurons were recorded from the monkey HF during virtual navigation in a similar situation to a rodent water maze, in which distal cues were important to locate the animal's position. A subset of 72 neurons displayed place-related activity in one or more virtual spaces. Most place-related responses disappeared or changed their spatial tuning (i.e., remapping) when the arrangements of the distal cues were altered/moved in the virtual spaces. These specific features of the monkey HF might underlie neurophysiological bases of human episodic memory.

Animals↗
PubMed2001

Quantitative cell dispersion analysis: new test to measure tumor cell aggressiveness.

Tumor progression requires the dispersion of epithelial cells from neoplastic clusters and cell invasion of adjacent stromal connective tissue. Aiming at demonstrating the precise relationships between cell dispersion and cell invasion, related respectively to expression of E-cadherin/catenin complex and matrix metalloproteinases (MMPs), we developed an original in vitro model of cell dispersion analysis. Our study reports the validation of this model that allowed us to analyze and quantify the cell cohesion level by means of time-lapse videomicroscopy and computer analysis based on the observation of spatial and temporal cell distribution. Our model was able to distinguish 2 groups among different human bronchial and mammary epithelial cells previously characterized for the expression of E-cadherin/catenin complex and MMPs and their invasive capacity in the Boyden chamber assay. The first group (16HBE14o(-), MCF-7, T47D) that expressed membranous E-cadherin and beta-catenin, and was negative for MMP-2 expression and non-invasive, displayed a highly cohesive pattern corresponding to a cluster spatial distribution. The second group (Beas2B, BZR, BZR-T33, MDA-MB-231, MDA-MB-435, BT549 and HS578T) that was invasive and showed lack of expression of E-cadherin and a cytoplasmic redistribution of beta-catenin, displayed a dispersed pattern corresponding to a random spatial distribution. Downregulation of E-cadherin by a blocking antibody induced a more random distribution. Conversely, expression of E-cadherin by cDNA transfection induced a cluster distribution. Moreover, tumor cell lines that co-expressed MT1-MMP and MMP-2 (Beas2B, BZR, BZR-T33, MDA-MB-435, BT549 and HS578T) showed a more dispersed pattern than tumor cell lines that did not express MMP-2 (MDA-MB-231). In conclusion, we demonstrated that the spatial group behavior of cell lines, i.e., their cohesion/dispersion ability, reflects their invasive properties. Thus, this model of cell dispersion analysis may represent a new test to measure tumor cell aggressiveness.

Breast↗
PubMed1988

Cellular mechanisms controlling the strength of synapses.

The mechanisms suspected as contributors to the regulation of synaptic strength act at a variety of sites along the causal chain that links activity in a presynaptic neuron to activity in a postsynaptic one. At several places in this chain, morphological factors are expected to have a powerful influence, and at several others, key insights into the mechanisms controlling synaptic action have been achieved using morphological techniques. A variety of presynaptic mechanisms controlling the release of neurotransmitter have been most directly shown to regulate the potency of synaptic connections. Traditional interpretations of the effect of postsynaptic geometry on synaptic strength need to be reevaluated in light of new views of the functional properties of dendritic membrane, and the new neurophysiological data must be incorporated into a more comprehensive view of the behavior of spatially distributed excitable membrane with specific patterns of distributed synaptic inputs.

Animals↗
PubMed2005

Mice with the deleted neurofilament of low molecular weight (Nefl) gene: 2. Effects on motor functions and spatial orientation.

Mice with a null mutation of the Nefl gene were compared with normal controls in tests of motor activity, equilibrium, and spatial orientation. Despite a normal capacity to ambulate, NFL -/- mice had fewer rears in an open field, crossed fewer segments on stationary beams, and fell more frequently when suspended on a horizontal bar. In addition, the distance swum before reaching the escape platform was greater in NFL -/- mice than in controls during acquisition of place learning in the Morris water maze at the start of training. The motor impairments were linearly correlated with increased cytochrome oxidase activity seen in cerebellum and brainstem. These results indicate that, as early as 6 months, depletion of the NFL protein is sufficient to cause mild sensorimotor dysfunctions and spatial deficits, but without overt signs of paresis.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Possible strategies for finding the substrate for learning-induced changes in the hippocampal cortex.

For long-lasting memory traces, structural synaptic changes remain a probable mechanism. However, in higher animals it has proved difficult to provide positive evidence for this notion. The main reason may be that the changes are subtle and are to be found in a relatively small subset of synapses and in a distributed manner in the cellular network in question. Here, we discuss possible strategies for finding structural changes in the hippocampus associated with spatial learning, an activity for which this structure is important. Spatial learning may induce new excitatory synapses in a small subset of hippocampal CA1 neurons because we observe a higher spine density without alteration in dendritic length or branching. The dendritic synapses are regularly spaced, irrespective of spine density, suggesting the operation of an intersynaptic dispersing force.

Animals↗
PubMed1981

Personal space preferences of hospitalized adults.

The questions addressed in this study were whether hospitalized adults' personal space preferences (PSP) differed between the hospital and home setting and whether these patients assigned different PSP to a nurse, doctor, family member, or stranger. The effects of age and sex of the subjects were also examined. Sixty subjects (30 men and 30 women) meeting selected criteria participated. The figure-placement technique (Little, 1965; Guardo, 1976) was used to measure PSP. Data were analyzed using a four-factor ANOVA (age X sex X role X setting) with repeated measures on the last two factors. Main effects were found fer setting, F(1,54) = 11.54, p less than .001, and role, F(3,162) = 112.95, p less than .0001; no other variables approached statistical significance. The major findings indicated that preferred distances in the hospital were smaller than in the home and that in both settings the family member was placed closest to the "self" silhousette followed by a doctor, nurse, and stranger, respectively.

Adolescent↗
PubMed2003

D1 dopamine receptors in the mouse prefrontal cortex: Immunocytochemical and cognitive neuropharmacological analyses.

Dopamine D1 receptors have critical neuromodulatory influences on the working memory functions of the prefrontal cortex, a brain region affected in many neuropsychiatric disorders. When D1 receptor agents are administered to rats or monkeys performing working memory tasks, an "inverted U" dose/response function is typically observed, whereby either too little or too much D1 receptor stimulation impairs working memory. There are two subtypes of D1 receptors, the D1A and the D1B (also known as the D1 and D5, respectively), but the relative contributions of these subtypes to prefrontal cortical function are not known, as there are no pharmacological agents that can distinguish between these receptors. Thus, genetically altered mice are needed to address this question. However, it is not known whether the mouse prefrontal cortex contains both D1A and D1B receptor subtypes, nor is it known whether mice will exhibit responses to D1 receptor agonists similar to those seen in rats and monkeys. The current study examined these issues by immunostaining the mouse brain with specific antibodies directed at the D1A and D1B receptor subtypes and by assessing the effects of increasing doses of a D1 receptor agonist, SKF81297, on spatial working memory performance in mice. Results indicate that mice are generally similar to monkeys and rats, expressing both D1A and D1B receptors in the prefrontal cortex and exhibiting an inverted "U" dose/response curve when administered SKF81297.

Animals↗
PubMed2003

Developmental D-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.

In previous studies, we have shown that P11-20 treatment with D-methamphetamine (MA) (10 mg/kg x 4/day at 2-h intervals) induces impairments in spatial learning and memory in the Morris water maze after the offspring reach adulthood. Using a split-litter, multiple dose, design (0, 5, 10, and 15 mg/kg MA administered s.c. 4/day at 2-h intervals), the spatial learning effect was further explored with a multiple shifted platform (reversal), reference memory-based procedure and a working memory procedure. Prior to spatial learning, animals were first tested for swimming ability (in a straight swimming channel), sequential learning (in the Cincinnati multiple-T water maze), and proximal cue learning (in the Morris water maze). Rats were then assessed in the hidden platform, reference memory-based spatial version of the Morris maze for acquisition and on five subsequent phases in which the platform was moved to new locations. After the reference memory-based, fixed platform position learning phases, animals were tested in the trial-dependent, matching-to-sample, working memory version of the Morris maze. No group differences were found in straight channel, sequential maze, or cued Morris maze performance. By contrast, all MA groups were impaired in spatial learning during acquisition, multiple shift, and shifted with a reduced platform phases of reference memory-based learning. In addition, MA animals were impaired on memory (probe) trials during the acquisition and shifted with a reduced platform phases of learning. No effects on trial-dependent, matching-to-sample, working memory were found. The findings demonstrate that neonatal treatment with MA induces a selective impairment of reference memory-based spatial learning while sparing sequential, cued, and working memory-based learning.

Animals↗
PubMed1994

Comparison of four spatial maze learning tests with methylnitrosourea-induced microcephaly rats.

The usefulness of four spatial maze learning test methods, single T-maze, Biel water maze, Morris water maze, and radial eight-arm maze, was compared using rats with different degrees of microcephaly, which were induced by single intraperitoneal injection with 3 and 5 mg/kg of methylnitrosourea (MNU) on day 13 of gestation. The single T-maze test did not detect a learning defect in either MNU group. In the Biel water maze test, the swimming time and number of errors were increased in the 5 mg/kg group, but these parameters were comparable to the control values in the retention and path B (reverse course) tests. On the Morris water maze task, the 5 mg/kg group required longer swimming time and distance to reach the goal. In the retest with the goal set on an opposite side, the swimming distance in the 5 mg/kg group was as long as the value in the original test. The radial eight-arm maze test detected fewer correct choices in both MNU groups, which showed different responses on this task. The brain weights in the 3 and 5 mg/kg groups were approximately 80 and 60% of the control value, respectively. The cerebral cortex weights were 77 and 50% of the control value, and the hippocampus weights were 78 and 51%. Among the four maze tests, only the radial eight-arm maze test could detect the effect of both doses of MNU. This shows that the method has the highest sensitivity to spatial learning defect in MNU-induced microcephalic rats.

Abnormalities, Drug-Induced↗
PubMed1998

Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery.

Erythropoietin (EPO) prevents the ischemia-induced delayed neuronal death in the hippocampal CA1 field in gerbils. EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known. To examine whether EPO has a neuroprotective action in the cortex, EPO was infused into the cerebroventricles of stroke-prone spontaneously hypertensive rats with permanent occlusion of the left middle cerebral artery. Morris water maze test indicated that EPO infusion alleviated the ischemia-induced place navigation disability. The left (ischemic)-to-right (contralateral nonischemic) (L/R) ratio of cerebrocortical area in the EPO-infused ischemic group was larger than that in the vehicle-infused ischemic group. The occlusion caused secondary thalamic degeneration but infusion of EPO prevented the decrease in the L/R ratio of thalamic area and supported neuron survival in the ventroposterior thalamic nucleus. In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging.

Animals↗
PubMed1995

An investigation of differences between three age groups in verbal and spatial task performance using the dual-task paradigm.

A dual-task paradigm with concurrent verbal and spatial tasks was used to investigate differences across three age groups for lateralized effects, magnitude of tapping interference, and cognitive task output. In addition, rescaled scores comparing verbal with spatial measures within and across age groups were analyzed to examine asymmetric age differences for right versus left hemisphere abilities. Results of the present dual task finger tapping investigation of three age groups showed all groups left lateralized for verbal tasks and right lateralized for spatial tasks. However, the magnitude of interference in tapping was significantly greater in paced nonideational shadowing tasks and during paced purposeful spatial tasks. Outcomes of exploratory analyses suggest a complex interplay between aptitude and the corresponding lateralized effects and cognitive effort to perform the task.

Adolescent↗
PubMed1998

Analysis of primary and secondary influences on spatial neglect.

When attempting to determine the middle of a line, patients with neglect deviate from true center. Deviation may be induced by perceptual-attentional bias, premotor-intentional bias, or both. Using a video-based apparatus, we decoupled perceptual from premotor influences on line bisection performance in patients with hemispatial neglect to examine (a) the relationship between primary and secondary bias and (b) the relationship of bias type to lesion location. The same video-based procedure was applied to target cancellation to determine if neglect type varied as a function of task. Primary attentional-perceptual bias was found using line bisection in 14/26 subjects, most of whom had lesions involving the posterior hemisphere. Primary premotor-intentional bias on line bisection was more often associated with lesions of frontal-subcortical structures. The neglect type determined by the bisection task agreed with the results of target cancellation in most cases. Secondary bias was determined based upon whether decoupling decreased the magnitude of bisection error (concordant), increased error (discordant), or produced no significant change. Most patients showed a secondary bias, with 12/26 in the discordant group and 11/26 in the concordant group. Discordant secondary bias was more common in premotor-intentional neglect (10/12) than in perceptual-attentional neglect (2/14), whereas concordant bias was more common in the latter group (10/14) compared to the former (1/12). The nonrandom relationship between primary and secondary bias may provide a more detailed description of ways in which anatomically separate components of a cortical network contribute to spatial processing under conditions of perceptuomotor incongruity.

Brain↗