SEARCH · PubMed Health

Results for “spatial dependency”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed2006

Impairment of spatial learning and memory in ELKL Motif Kinase1 (EMK1/MARK2) knockout mice.

The hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer's disease (AD) and of the associated cognitive decline. EMK1 (MARK2) is a serine/threonine kinase which phosphorylates tau and MAP2. An involvement of this kinase in memory functions is not established. We used a behavioral approach to study the phenotype of EMK1-null mice (EMK1-KO) as a possible model of MAP2/tau altered phophorylation. Compared to wild type mice, EMK1-KO mice did not differ in non-cognitive aspects of behavior, such as locomotion in activity cages, or anxiety in the elevated plus maze. However, they exhibited lower performance in the first stage of acquisition of a hippocampal-dependent spatial learning, as assessed in a radial water maze, although, they acquired the task with repeated training. They were again found to be impaired on re-learning a new platform position. In addition, they exhibited poor long-term retention performance. These data underline the importance on both early memory processes and long-term retrieval, of the dynamic instability of microtubules generated by the phosphorylation of MAPs.

Analysis of Variance↗

PubMed2004

Structural remodeling of mouse gracilis artery after chronic alteration in blood supply.

The goals of this study were to determine the time course and spatial dependence of structural diameter changes in the mouse gracilis artery after a redistribution of blood flow and to compare the observations with predictions of computational models for structural adaptation. Diameters were measured 1, 2, 7, 14, 21, 28, and 56 days after resection of one of the two blood supplies to the artery. Overall average diameter, normalized with respect to diameters in untreated vessels, increased slightly during the first 7 days, then increased more rapidly, reaching a peak around day 21, and then decreased. This transient increase in diameter was spatially nonuniform, being largest toward the point of resection. A previously developed theoretical model, in which diameter varies in response to stimuli derived from local metabolic and hemodynamic conditions, was extended to include effects of time-delayed remodeling stimuli in regions of reduced perfusion. Predictions of this model were consistent with observed diameter changes, including the transient increase in diameters near the point of resection, when a remodeling stimulus with a time delay of approximately 7 days was included. The results suggest that delayed stimuli significantly influence the dynamic characteristics of vascular remodeling resulting from reduced blood supply.

Adaptation, Physiological↗

PubMed2004

A comparison of GluR-A-deficient and wild-type mice on a test battery assessing sensorimotor, affective, and cognitive behaviors.

Previous studies have demonstrated a spatial working memory deficit in glutamate receptor (GluR)-A (GluR1) AMPA receptor subunit knockout mice. The present study evaluated male and female wild-type and GluR-A-/- mice on a test battery that assessed sensorimotor, affective, and cognitive behaviors. Results revealed a behavioral phenotype more extensive than previously described. GluR-A-/- mice were hyperactive, displayed a subtle lack of motor coordination, and were generally more anxious than wild-type controls. In addition, they showed a deficit in spontaneous alternation, consistent with previous reports of a role for GluR-A-dependent plasticity in hippocampus-dependent, spatial working memory. Although changes in motor coordination or anxiety cannot explain the dissociations already reported within the spatial memory domain, it is clear that they could significantly affect interpretation of results obtained in other kinds of behavioral tasks.

Affect↗

PubMed2004

Frequency and spatial distribution of environmental Campylobacter spp.

Humans are exposed to Campylobacter spp. in a range of sources via both food and environmental pathways. For this study, we explored the frequency and distribution of thermophilic Campylobacter spp. in a 10- by 10-km square rural area of Cheshire, United Kingdom. The area contains approximately 70, mainly dairy, farms and is used extensively for outdoor recreational activities. Campylobacter spp. were isolated from a range of environmental samples by use of a systematic sampling grid. Livestock (mainly cattle) and wildlife feces and environmental water and soil samples were cultured, and isolates were presumptively identified by standard techniques. These isolates were further characterized by PCR. Campylobacter jejuni was the most prevalent species in all animal samples, ranging from 11% in samples from nonavian wildlife to 36% in cattle feces, and was isolated from 15% of water samples. Campylobacter coli was commonly found in water (17%) and sheep (21%) samples, but rarely in other samples. Campylobacter lari was recovered from all sample types, with the exception of sheep feces, and was found in moderate numbers in birds (7%) and water (5%). Campylobacter hyointestinalis was only recovered from cattle (7%) and birds (1%). The spatial distribution and determinants of C. jejuni in cattle feces were examined by the use of model-based spatial statistics. The distribution was consistent with very localized within-farm or within-field transmission and showed little evidence of any larger-scale spatial dependence. We concluded that there is a potentially high risk of human exposure to Campylobacter spp., particularly C. jejuni, in the environment of our study area. The prevalence and likely risk posed by C. jejuni-positive cattle feces in the environment diminished as the fecal material aged. After we took into account the age of the fecal material, the absence or presence of rain, and the presence of bird feces, there was evidence of significant variation in the prevalence of C. jejuni-positive cattle feces between grazing fields but no evidence of spatial clustering beyond this resolution. The spatial pattern of C. jejuni is therefore consistent with that for an organism that is ubiquitous in areas contaminated with cattle feces, with a short-scale variation in infection intensity that cannot be explained solely by variations in the age of the fecal material. The observed pattern is not consistent with large-scale transmission attributable to watercourses, wildlife territories, or other geographical features that transcend field and farm boundaries.

Animals↗

PubMed2004

Coordination of cell signaling, chromatin remodeling, histone modifications, and regulator recruitment in human matrix metalloproteinase 9 gene transcription.

Transcriptional activation of eukaryotic genes depends on the precise and ordered recruitment of activators, chromatin modifiers/remodelers, coactivators, and general transcription factors to the promoters of target genes. Using the human matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the sequential assembly and dynamic formation of transcription complexes on a human promoter under the influence of mitogen signaling. We find that, coincident with activation of the MMP-9 gene, activators, chromatin remodeling complexes, and coactivators are recruited to the preassembled MMP-9 promoter in a stepwise and coordinated order, which is dependent on activation of MEK-1/extracellular signal-regulated kinase and NF-kappa B signaling pathways. Conversely, corepressor complexes are released from the MMP-9 promoter after transcriptional activation. Histone modifications shift from repressive to permissive modifications concurrent with activation of the MMP-9 gene. Chromatin remodeling induced by Brg-1 is required for MMP-9 gene transcription, which is concomitant with initiation of transcription. Therefore, coordination of cell signaling, chromatin remodeling, histone modifications, and stepwise recruitment of transcription regulators is critical to precisely regulate MMP-9 gene transcription in a temporally and spatially dependent manner. Given the important role of MMP-9 in both normal development and pathological conditions, understanding MMP-9 gene regulation is of great relevance.

Binding Sites↗

PubMed1995

Protein kinase C in the hippocampus is altered by spatial but not cued discriminations: a component task analysis.

The exact role of the mammalian hippocampus in memory formation remains essentially as an unanswered question for cognitive neuroscience. Experiments with humans and with animals indicate that some types of mnemonic associative processes involve hippocampal function while others do not. Support for the spatial processing hypothesis of hippocampal function has stemmed from the impaired performance of rats with hippocampal lesions in tasks that require spatial discriminations, but not cued discriminations. Previous procedures, however, have confounded the interpretation of spatial versus cued discrimination learning with the number and kinds of irrelevant stimuli present in the discrimination. An empirical set of data describing a role of protein kinase C (PKC) in different mnemonic processes is similarly being developed. Recent work has implicated the activation of this serine-threonine kinase in a variety of learning paradigms, as well as long-term potentiation (LTP), a model system for synaptic plasticity which may subserve some types of learning. The present study employs the principles of component task analysis to examine the role of membrane-associated PKC (mPKC) in hippocampal-dependent memory when all factors other than the type of learning were equivalent. The results indicate that hippocampal mPKC is altered by performance in hippocampally-dependent spatial discriminations, but not hippocampally-independent cued discriminations and provide a general experimental procedure to relate neural changes to specific behavioral changes.

Animals↗

PubMed2004

Intraseptal muscarinic ligands and galanin: influence on hippocampal acetylcholine and cognition.

The cholinergic neurons in the septohippocampal projection are implicated in hippocampal functions such as spatial learning and memory. The aim of this study was to examine how septohippocampal cholinergic transmission is modulated by muscarinic inputs and by the neuropeptide galanin, co-localized with acetylcholine (ACh) in septohippocampal cholinergic neurons, and how spatial learning assessed by the Morris water maze test is affected. Muscarinic inputs to the septal area are assumed to be excitatory, whereas galanin is hypothesized to inhibit septohippocampal cholinergic function. To test these hypotheses, compounds were microinjected into the medial septum and hippocampal ACh release was assessed by microdialysis probes in the ventral hippocampus of the rat. Blockade of septal muscarinic transmission by intraseptal scopolamine increased hippocampal ACh release suggesting that septal cholinergic neurons are under tonic inhibition. Stimulation of septal muscarinic receptors by carbachol also increased hippocampal ACh release. Despite this increase, both scopolamine and carbachol tended to impair hippocampus-dependent spatial learning. This finding also suggests a revision of the simplistic notion that an increase in hippocampal ACh may be facilitatory for learning and memory. Galanin infused into the medial septum enhanced hippocampal ACh release and facilitated spatial learning, suggesting that septal galanin, contrary to earlier claims, does not inhibit but excites septohippocampal cholinergic neurons. Galanin receptor stimulation combined with muscarinic blockade in the septal area resulted in an excessive increase of hippocampal ACh release combined with an impairment of spatial learning. This finding suggests that the level of muscarinic activity within the septal area may determine the effects of galanin on hippocampal cognitive functions. In summary, a limited range of cholinergic muscarinic transmission may contribute to optimal hippocampal function, a finding that has important implications for therapeutic approaches in the treatment of disorders of memory function.

Acetylcholine↗

PubMed2003

Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS.

The immediate early gene c-fos is part of the activator protein-1 transcription factor and has been postulated to participate in the molecular mechanisms of learning and memory. To test this hypothesis in vivo, we generated mice with a nervous system-specific c-fos knock-out using the Cre-loxP system. Adult mice lacking c-Fos in the CNS (c-fosDeltaCNS) showed normal general and emotional behavior but were specifically impaired in hippocampus-dependent spatial and associative learning tasks. These learning deficits correlated with a reduction of long-term potentiation (LTP) in hippocampal CA3-CA1 synapses. The magnitude of LTP was restored by a repeated tetanization procedure, suggesting impaired LTP induction in c-fosDeltaCNS mice. This rescue was blocked by a selective inhibitor of NR2B-type NMDA receptors. This blockade was compensated in wild-type mice by NR2A-type NMDA receptor-activated signaling pathways, thus indicating that these pathways are compromised in c-fosDeltaCNS mice. In summary, our data suggest a role for c-Fos in hippocampus-dependent learning and memory as well as in NMDA receptor-dependent LTP formation.

Animals↗

PubMed2000

Fast subsystem bifurcations in strongly coupled heterogeneous collections of excitable cells.

A continuum model for a heterogeneous collection of excitable cells electrically coupled through gap junctions is introduced and analysed using spatial averaging, asymptotic and numerical techniques. Heterogeneity is modelled by imposing a spatial dependence on parameters which define the single cell model and a diffusion term is used to model the gap junction coupling. For different parameter values, single cell models can exhibit bursting, beating and a myriad of other complex oscillations. A procedure for finding asymptotic estimates of the thresholds between these (synchronous) behaviors in the cellular aggregates is described for the heterogeneous case where the coupling strength is strong. This procedure is tested on a model of a strongly coupled heterogeneous collection of bursting and beating cells. Since isolated pancreatic beta-cells have been observed to both burst and beat, this test of the spatial averaging techniques provides a possible explanation to measured discrepancies between the electrical activities of isolated beta-cells and coupled collections (islets) of beta-cells.

Computer Simulation↗

PubMed2000

Functional inactivation of dorsal hippocampus impairs active place avoidance in rats.

This paper assesses the contribution of hippocampus to the spatial orientation of Long-Evans rats in a new place avoidance task. The animals learn to avoid a mild footshock in a segment of a rotating arena. Since the punished region is defined in the coordinate system of the stationary room the subject is forced to move away from the prohibited segment even if it is immobile. After bilateral injection of tetrodotoxin (5 ng in 1 microl of saline) into the dorsal hippocampus rats were not able to avoid the punished place while a similar injection of saline did not affect performance. The results suggest the task is suitable for assessing the hippocampus-dependent spatial abilities of laboratory rodents.

Animals↗

PubMed2005

Voting and catalytic processes with inhomogeneities.

We consider the dynamics of the voter model and of the monomer-monomer catalytic process in the presence of many "competing" inhomogeneities and show, through exact calculations and numerical simulations, that their presence results in a non-trivial fluctuating steady state whose properties are studied and turn out to specifically depend on the dimensionality of the system, the strength of the inhomogeneities, and their separating distances. In fact, in arbitrary dimensions, we obtain an exact (yet formal) expression of the order parameters (magnetization and concentration of adsorbed particles) in the presence of an arbitrary number n of inhomogeneities ("zealots" in the voter language) and formal similarities with suitable electrostatic systems are pointed out. In the non-trivial cases n = 1,2, we explicitly compute the static and long-time properties of the order parameters and therefore capture the generic features of the systems. When n > 2 , the problems are studied through numerical simulations. In one spatial dimension, we also compute the expressions of the stationary order parameters in the completely disordered case, where n is arbitrary large. Particular attention is paid to the spatial dependence of the stationary order parameters and formal connections with electrostatics.

Journal Article↗

PubMed2006

Aging-dependent alterations in synaptic plasticity and memory in mice that overexpress extracellular superoxide dismutase.

Oxidative damage caused by reactive oxygen species (ROS) has been proposed to be critically involved in several pathological manifestations of aging, including cognitive dysfunction. ROS, including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. Therefore, we reasoned that the role that ROS and antioxidant enzymes play in modulating neuronal processes varies over the lifespan of an animal. We examined hippocampal long-term potentiation (LTP) and memory-related behavioral performance in transgenic mice overexpressing extracellular superoxide dismutase (EC-SOD) and their wild-type littermates at different ages. We found that aged EC-SOD transgenic mice exhibited enhanced hippocampal LTP, better cerebellum-dependent motor learning, and better hippocampus-dependent spatial learning compared with their wild-type littermates. We also found that EC-SOD overexpression impaired contextual learning, but the impairment was decreased in the aged transgenic mice. At the molecular level, aged EC-SOD transgenic mice had lower superoxide levels, a decrease in protein carbonyl levels, and a decrease in p38 and extracellular signal-regulated kinase 2 phosphorylation compared with aged wild-type mice. Our findings suggest that elevated levels of superoxide contribute to aging-related impairments in hippocampal LTP and memory, and that these impairments can be alleviated by overexpression of EC-SOD. We conclude that there is an age-dependent alteration in the role of superoxide in modulating synaptic plasticity and learning and memory.

Aging↗

PubMed2004

Spatial learning impairment induced by chronic stress is related to individual differences in novelty reactivity: search for neurobiological correlates.

Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothesized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find a neurobiological substrate that specifically correlated with the differential cognitive vulnerability to chronic stress shown by animals with a different novelty reactivity, this study confirms the hypothesis that rats differ in their susceptibility to display stress-induced impairments in hippocampus-dependent spatial learning tasks. In addition, it provides a model to further search for the neurobiological substrate(s) involved in the differential susceptibility to develop stress-induced cognitive impairments.

Analysis of Variance↗

PubMedDate not supplied

An empirical evaluation of various priors in the empirical Bayes estimation of small area disease risks.

Empirical and fully Bayes estimation of small area disease risks places a prior distribution on area-specific risks. Several forms of priors have been used for this purpose including gamma, log-normal and non-parametric priors. Spatial correlation among area-specific risks can be incorporated in log-normal priors using Gaussian Markov random fields or other models of spatial dependence. However, the criterion for choosing one prior over others has been mostly logical reasoning. In this paper, we evaluate empirically the various priors used in the empirical Bayes estimation of small area disease risks. We utilize a Spanish mortality data set of a 12-year period to give the underlying true risks, and estimate the true risks using only a 3-year portion of the data set. Empirical Bayes estimates are shown to have substantially smaller mean squared errors than Poisson likelihood-based estimates. However, relative performances of various priors differ across a variety of mortality outcomes considered. In general, the non-parametric prior provides good estimates for lower-risk areas, while spatial priors provide good estimates for higher-risk areas. Ad hoc composite estimates averaging the estimates from the non-parametric prior and those from a spatial log-normal prior appear to perform well overall. This suggests that an empirical Bayes prior that strikes a balance between these two priors, if one can construct such a prior, may prove to be useful for the estimation of small area disease risks.

Adult↗

PubMed2003

Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.

The acid-sensing ion channel, ASIC1, contributes to synaptic plasticity in the hippocampus and to hippocampus-dependent spatial memory. To explore the role of ASIC1 in brain, we examined the distribution of ASIC1 protein. Surprisingly, although ASIC1 was present in the hippocampal circuit, it was much more abundant in several areas outside the hippocampus. ASIC1 was enriched in areas with strong excitatory synaptic input such as the glomerulus of the olfactory bulb, whisker barrel cortex, cingulate cortex, striatum, nucleus accumbens, amygdala, and cerebellar cortex. Because ASIC1 levels were particularly high in the amygdala, we focused further on this area. We found that extracellular acidosis elicited a greater current density in amygdala neurons than hippocampal neurons and that disrupting the ASIC1 gene eliminated H+-evoked currents in the amygdala. We also tested the effect of ASIC1 on amygdala-dependent behavior; ASIC1-null mice displayed deficits in cue and context fear conditioning, yet baseline fear on the elevated plus maze was intact. These studies suggest that ASIC1 is distributed to regions supporting high levels of synaptic plasticity and contributes to the neural mechanisms of fear conditioning.

Acid Sensing Ion Channels↗

PubMed2004

Pentyl-4-yn-valproic acid reverses age-associated memory impairment in the Wistar rat.

Pentyl-4-yn-valproic acid (VPA), a cognition-enhancing agent whose mode of action has been attributed to cell adhesion molecule-mediated neuritogenesis, has been shown to enhance hippocampus-dependent spatial learning. Here, we investigated its potential to reverse age-related memory impairment that relates mainly to declarative memory. Aged spatial learning deficits in the water maze paradigm were demonstrated by swim angle analysis, the angle between axes of start-to-platform and start-to-animal position, and latency to reach a submerged platform. Chronic pentyl-4-yn-VPA administration mediated a significant improvement in both search strategy and latency to find the submerged platform in aged animals. Pentyl-4-yn-VPA also facilitated task recall in aged animals as evidenced by increased time in the target quadrant during a probe trial 3 days following the final training session. The action of pentyl-4-yn-VPA on platform latency, search strategy and task recall suggests that this agent may have great benefit in the treatment of age-dependent cognitive decline.

Aging↗

PubMed1995

Spatial and temporal factors determine auditory-visual interactions in human saccadic eye movements.

In this paper, we show that human saccadic eye movements toward a visual target are generated with a reduced latency when this target is spatially and temporally aligned with an irrelevant auditory nontarget. This effect gradually disappears if the temporal and/or spatial alignment of the visual and auditory stimuli are changed. When subjects are able to accurately localize the auditory stimulus in two dimensions, the spatial dependence of the reduction in latency depends on the actual radial distance between the auditory and the visual stimulus. If, however, only the azimuth of the sound source can be determined by the subjects, the horizontal target separation determines the strength of the interaction. Neither saccade accuracy nor saccade kinematics were affected in these paradigms. We propose that, in addition to an aspecific warning signal, the reduction of saccadic latency is due to interactions that take place at a multimodal stage of saccade programming, where the perceived positions of visual and auditory stimuli are represented in a common frame of reference. This hypothesis is in agreement with our finding that the saccades often are initially directed to the average position of the visual and the auditory target, provided that their spatial separation is not too large. Striking similarities with electrophysiological findings on multisensory interactions in the deep layers of the midbrain superior colliculus are discussed.

Adult↗

PubMed2006

Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients.

Axonal degeneration of white matter fibers is a key consequence of neuronal or axonal injury. It is characterized by a series of time-related events with initial axonal membrane collapse followed by myelin degradation being its major hallmarks. Standard imaging cannot differentiate these phenomena, which would be useful for clinical investigations of degeneration, regeneration and plasticity. Animal models suggest that diffusion tensor magnetic resonance imaging (DTI) is capable of making such distinction. The applicability of this technique in humans would permit inferences on white matter microanatomy using a non-invasive technique. The surgical bisection of the anterior 2/3 of the corpus callosum for the palliative treatment of certain types of epilepsy serves as a unique opportunity to assess this method in humans. DTI was performed on three epilepsy patients before corpus callosotomy and at two time points (1 week and 2-4 months) after surgery. Tractography was used to define voxels of interest for analysis of mean diffusivity, fractional anisotropy and eigenvalues. Diffusion anisotropy was reduced in a spatially dependent manner in the genu and body of the corpus callosum at 1 week and remained low 2-4 months after the surgery. Decreased anisotropy at 1 week was due to a reduction in parallel diffusivity (consistent with axonal fragmentation), whereas at 2-4 months, it was due to an increase in perpendicular diffusivity (consistent with myelin degradation). DTI is capable of non-invasively detecting, staging and following the microstructural degradation of white matter following axonal injury.

Adult↗