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PubMed1997

Mechanisms of electrical coupling between pyramidal cells.

Direct electrical coupling between neurons can be the result of both electrotonic current transfer through gap junctions and extracellular fields. Intracellular recordings from CA1 pyramidal neurons of rat hippocampal slices showed two different types of small-amplitude coupling potentials: short-duration (5 ms) biphasic spikelets, which resembled differentiated action potentials and long-duration (>20 ms) monophasic potentials. A three-dimensional morphological model of a pyramidal cell was employed to determine the extracellular field produced by a neuron and its effect on a nearby neuron resulting from both gap junctional and electric field coupling. Computations were performed with a novel formulation of the boundary element method that employs triangular elements to discretize the soma and cylindrical elements to discretize the dendrites. An analytic formula was derived to aid in computations involving cylindrical elements. Simulation results were compared with biological recordings of intracellular potentials and spikelets. Field effects produced waveforms resembling spikelets although of smaller magnitude than those recorded in vitro. Gap junctional electrotonic connections produced waveforms resembling small-amplitude excitatory postsynaptic potentials. Intracellular electrode measurements were found inadequate for ascertaining membrane events because of externally applied electric fields. The transmembrane voltage induced by the electric field was highly spatially dependent in polarity and wave shape, as well as being an order of magnitude larger than activity measured at the electrode. Membrane voltages because of electrotonic current injection across gap junctions were essentially constant over the cell and were accurately depicted by the electrode. The effects of several parameters were investigated: 1) decreasing the ratio of intra to extracellular conductivity reduced the field effects; 2) the tree structure had a major impact on the intracellular potential; 3) placing the gap junction in the dendrites introduced a time delay in the gap junctional mediated electrotonic potential, as well as deceasing the potential recorded by the somatic electrode; and 4) field effects decayed to one-half of their maximum strength at a cell separation of approximately 20 micron. Results indicate that the in vitro measured spikelets are unlikely to be mediated by gap junctions and that a spikelet produced by the electric field of a single source cell has the same waveshape as the measured spikelet but with a much smaller amplitude. It is hypothesized that spikelets are a manifestation of the simultaneous electric field effects from several local cells whose action potential firing is synchronized.

Action Potentials↗

PubMed2006

Cognition and the sex chromosomes: studies in Turner syndrome.

Turner syndrome (TS) is a human genetic disorder involving females who lack all or part of one X chromosome. The complex phenotype includes ovarian failure, a characteristic neurocognitive profile and typical physical features. TS features are associated not only with complete monosomy X but also with partial deletions of either the short (Xp) or long (Xq) arm (partial monosomy X). Impaired visual-spatial/perceptual abilities are characteristic of TS children and adults of varying races and socioeconomic status, but global developmental delay is uncommon. The cognitive phenotype generally includes normal verbal function with relatively impaired visual-spatial ability, attention, working memory, and spatially dependent executive function. The constellation of neurocognitive deficits observed in TS is most likely multifactorial and related to a complex interaction between genetic abnormalities and hormonal deficiencies. Furthermore, other determinants, including an additional genetic mechanism, imprinting, may also contribute to cognitive deficits associated with monosomy X. As a relatively common genetic disorder with well-defined manifestations, TS presents an opportunity to investigate genetic and hormonal factors that influence female cognitive development. TS is an excellent model for such studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. In the current review, we summarize the hormonal and genetic factors that may contribute to the TS neurocognitive phenotype. The hormonal determinants of cognition in TS are related to estrogen and androgen deficiency. Our genetic hypothesis is that haploinsufficiency for gene/genes on the short arm of the X chromosome (Xp) is responsible for the hallmark features of the TS cognitive phenotype. Careful clinical and molecular characterization of adult subjects missing part of Xp links the TS phenotype of impaired visual spatial/perceptual ability to specific distal Xp chromosome regions. We demonstrate that small, nonmosaic deletion of the distal short arm of the X chromosome in adult women is associated with the same hallmark cognitive profile seen in adult women with TS. Future studies will elucidate the cognitive deficits and the underlying etiology. These results should allow us to begin to design cognitive interventions that might lessen those deficits in the TS population.

Adult↗

PubMed2006

What is the functional significance of chronic stress-induced CA3 dendritic retraction within the hippocampus?

Chronic stress produces consistent and reversible changes within the dendritic arbors of CA3 hippocampal neurons, characterized by decreased dendritic length and reduced branch number. This chronic stress-induced dendritic retraction has traditionally corresponded to hippocampus-dependent spatial memory deficits. However, anomalous findings have raised doubts as to whether a CA3 dendritic retraction is sufficient to compromise hippocampal function. The purpose of this review is to outline the mechanism underlying chronic stress-induced CA3 dendritic retraction and to explain why CA3 dendritic retraction has been thought to mediate spatial memory. The anomalous findings provide support for a modified hypothesis, in which chronic stress is proposed to induce CA3 dendritic retraction, which then disrupts hypothalamic-pituitary-adrenal axis activity, leading to dysregulated glucocorticoid release. The combination of hippocampal CA3 dendritic retraction and elevated glucocorticoid release contributes to impaired spatial memory. These findings are presented in the context of clinical conditions associated with elevated glucocorticoids.

Adaptation, Physiological↗

PubMed2006

Microarray image analysis: background estimation using quantile and morphological filters.

BACKGROUND: In a microarray experiment the difference in expression between genes on the same slide is up to 103 fold or more. At low expression, even a small error in the estimate will have great influence on the final test and reference ratios. In addition to the true spot intensity the scanned signal consists of different kinds of noise referred to as background. In order to assess the true spot intensity background must be subtracted. The standard approach to estimate background intensities is to assume they are equal to the intensity levels between spots. In the literature, morphological opening is suggested to be one of the best methods for estimating background this way. RESULTS: This paper examines fundamental properties of rank and quantile filters, which include morphological filters at the extremes, with focus on their ability to estimate between-spot intensity levels. The bias and variance of these filter estimates are driven by the number of background pixels used and their distributions. A new rank-filter algorithm is implemented and compared to methods available in Spot by CSIRO and GenePix Pro by Axon Instruments. Spot's morphological opening has a mean bias between -47 and -248 compared to a bias between 2 and -2 for the rank filter and the variability of the morphological opening estimate is 3 times higher than for the rank filter. The mean bias of Spot's second method, morph.close.open, is between -5 and -16 and the variability is approximately the same as for morphological opening. The variability of GenePix Pro's region-based estimate is more than ten times higher than the variability of the rank-filter estimate and with slightly more bias. The large variability is because the size of the background window changes with spot size. To overcome this, a non-adaptive region-based method is implemented. Its bias and variability are comparable to that of the rank filter. CONCLUSION: The performance of more advanced rank filters is equal to the best region-based methods. However, in order to get unbiased estimates these filters have to be implemented with great care. The performance of morphological opening is in general poor with a substantial spatial-dependent bias.

Algorithms↗

PubMed1998

A simple method for investigating the effects of non-uniformity of radiofrequency transmission and radiofrequency reception in MRI.

Inhomogeneity of the transmitted or received B1 field leads to intensity variations in MR images and spatial dependence in apparent concentration in MR spectra. We describe a simple method for investigating such variations. The transmitted B1 field can be measured both in vivo and in vitro which allows investigation of sample dependent effects that can not be measured on phantoms. For homogeneous regions the method also allows the received B1 field to be measured both in vivo and in vitro. Our method uses only a standard spin echo pulse sequence and simple region of interest analysis and should be implementable on any commercial scanner. The method is demonstrated using a variety of transmission and reception radiofrequency coils both in vivo and in vitro.

Head↗

PubMedDate not supplied

The role of metabotropic glutamate receptor 5 in learning and memory processes.

Metabotropic glutamate receptor 5 (mGluR5), a subtype in the group I mGluRs, couples to phospholipase C through Gq protein. Stimulation of mGluR5 leads to the release of calcium from intracellular stores and protein kinase C activation. In addition, links to different ion channels and other signaling mechanisms have also been revealed. MGluR5s are mainly localized postsynaptically on the periphery of synap-ses. MGluR5s have been implicated in synaptic plasticity and learning and memory. The development of the highly potent and selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has facilitated the understanding of the roles of mGluR5s in the central nervous system. Both in vitro and in vivo studies have demonstrated that the activation of mGluR5s is necessary for some forms of long-term potentiation and long-term depression in different brain regions. Investigations of the effects of MPEP in various behavioral paradigms have concluded that mGluR5s play a critical role in aversive learning tasks and in hippocampal-dependent spatial learning. However, MPEP has proved ineffective in certain other learning tasks. MGluR5 knockout mice have shown impairments in water maze and radial arm maze performance as well as in contextual fear conditioning, but not in cue conditioning. This review summarizes recent advances reported on mGluR5 function in synaptic plasticity, learning and memory. The current development of positive and negative allosteric modulators of mGluR5 will provide new pharmacological tools to enhance our knowledge of these receptors in physiological and pathophysiological processes and will further facilitate new investigations on mGluR5 as a therapeutic target for a range of neurological and psychological disorders.

Animals↗

PubMed2004

Using texture to analyze and manage large collections of remote sensed image and video data.

We describe recent research into using the visual primitive of texture to analyze and manage large collections of remote sensed image and video data. Texture is regarded as the spatial dependence of pixel intensity. It is characterized by the amount of dependence at different scales and orientations, as measured with frequency-selective filters. A homogeneous texture descriptor based on the filter outputs is shown to enable (1) content-based image retrieval in large collections of satellite imagery, (2) semantic labeling and layout retrieval in an aerial video management system, and (3) statistical object modeling in geographic digital libraries.

Journal Article↗

PubMed2006

Cavity with a deformable mirror for tailoring the shape of the eigenmode.

We demonstrate an optical cavity that supports an eigenmode with a flattop spatial profile--a profile that has been proposed for the cavities in the Advanced Laser Interferometer Gravitational Wave Observatory, the second-generation laser interferometric gravitational wave observatory--because it provides better averaging of the spatially dependent displacement noise on the surface of the mirror than a Gaussian beam. We describe the deformable mirror that we fabricated to tailor the shape of the eigenmode of the cavity and show that this cavity is a factor of 2 more sensitive to misalignments than a comparable cavity with spherical mirrors supporting an eigenmode with a Gaussian profile.

Journal Article↗

PubMed2002

Senescent changes in parafoveal color appearance: saturation as a function of stimulus area.

The chromatic content (saturation) of monochromatic stimuli (480, 505, 577, and 650 nm) was scaled as a function of field size at three different retinal locations by 58 observers ranging from 18 to 83 yr of age. The different retinal locations (6 deg nasal, 2.5 deg inferior and 6 deg temporal eccentricity) were chosen according to anatomical studies demonstrating different degrees of senescent losses of cones or ganglion cells. Nine field sizes were tested, ranging from 0.0096 to 0.96 deg in diameter. The subjects used a percentage scale to judge the saturation of the flashed stimulus presentations (2 s on, 5 s off). The data analysis demonstrated that older observers require larger field sizes than younger observers to perceive hue as well as larger field sizes to reach the same level of scaled saturation. The spatial dependency of color appearance for younger and older observers was not correlated with senescent losses in retinal cells reported for the different retinal locations. The data were modeled by using an impulse-response function (i.e., Naka-Rushton equation) so that perceptive fields could be compared to electrophysiological measures of receptive fields or dendritic fields of retinal and cortical cells.

Adult↗

PubMed2005

Estimation of kinetic model parameters in fluorescence optical diffusion tomography.

We present a technique for reconstructing the spatially dependent dynamics of a fluorescent contrast agent in turbid media. The dynamic behavior is described by linear and nonlinear parameters of a compartmental model or some other model with a deterministic functional form. The method extends our previous work in fluorescence optical diffusion tomography by parametrically reconstructing the time-dependent fluorescent yield. The reconstruction uses a Bayesian framework and parametric iterative coordinate descent optimization, which is closely related to Gauss-Seidel methods. We demonstrate the method with a simulation study.

Algorithms↗

PubMed2005

Passive mode-locking by use of waveguide arrays.

A novel mode-locking technique is presented in which the intensity-dependent spatial coupling dynamics of a waveguide array is used to achieve temporal mode-locking in a passive optical fiber laser. By use of the discrete, nearest-neighbor spatial coupling of the waveguide array, low-intensity light can be transferred to the neighboring waveguides and ejected (attenuated) from the laser cavity. In contrast, higher-intensity light is self-focused in the waveguide and remains largely unaffected. Numerical studies of this pulse shaping mechanism (intensity discrimination) show that using current waveguide arrays and standard optical fiber technology produces stable and robust mode-locked soliton-like pulses.

Journal Article↗

PubMed2004

Uncertainties in depth determination and comparison of multivariate with univariate analysis in confocal Raman studies of a laminated polymer and skin.

Confocal Raman microscopy data are reported for a laminated polymer (Paramount) and for pigskin. The nature of the laminated structure of the polymer provides a useful test for evaluation of thickness distortions in confocal measurements in soft samples, which are found to be quite significant. The spatial variation in line profiles generated from univariate analyses with scores derived from factor loadings are consistent for both samples and provide distinct diagnostic markers for stratum corneum and epidermis regions of skin. Univariate analysis of the C-C stretching region of skin reveals a spatial dependence of chain conformational order. In addition, variations in keratin-containing areas of the stratum corneum are readily identified from area maps of the S-S stretching vibrations. These data indicate that confocal Raman imaging studies of molecular structure changes in particular regions of skin during pathological processes will prove quite valuable in dermatology.

Animals↗

PubMed2006

Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.

Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.

Animals↗

PubMed2005

Hippocampal synaptic modulation by the phosphotyrosine adapter protein ShcC/N-Shc via interaction with the NMDA receptor.

N-Shc (neural Shc) (also ShcC), an adapter protein possessing two phosphotyrosine binding motifs [PTB (phosphotyrosine binding) and SH2 (Src homology 2) domains], is predominantly expressed in mature neurons of the CNS and transmits neurotrophin signals from the TrkB receptor to the Ras/mitogen-activated protein kinase (MAPK) pathway, leading to cellular growth, differentiation, or survival. Here, we demonstrate a novel role of ShcC, the modulation of NMDA receptor function in the hippocampus, using ShcC gene-deficient mice. In behavioral analyses such as the Morris water maze, contextual fear conditioning, and novel object recognition tasks, ShcC mutant mice exhibited superior ability in hippocampus-dependent spatial and nonspatial learning and memory. Consistent with this finding, electrophysiological analyses revealed that hippocampal long-term potentiation in ShcC mutant mice was significantly enhanced, with no alteration of presynaptic function, and the effect of an NMDA receptor antagonist on its expression in the mutant mice was notably attenuated. The tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B was also increased, suggesting that ShcC mutant mice have enhanced NMDA receptor function in the hippocampus. These results indicate that ShcC not only mediates TrkB-Ras/MAPK signaling but also is involved in the regulation of NMDA receptor function in the hippocampus via interaction with phosphotyrosine residues on the receptor subunits and serves as a modulator of hippocampal synaptic plasticity underlying learning and memory.

Amino Acid Motifs↗

PubMed2004

Observation of magnetoreceptive behavior in a multicellular magnetotactic prokaryote in higher than geomagnetic fields.

The magnetotactic multicellular prokaryote (MMP), a motile aggregate of bacterial cells, is known to exhibit an unusual "ping-pong" motility in magnetic fields greater than the earth's field. This motility is characterized by rapid excursions, opposite the direction of an applied magnetic field, and slower returns along the direction of the magnetic field. We have carried out detailed observations of the time and spatial dependence of the ping-pong motility and find 1), the outward and return excursions exhibit a uniform deceleration and acceleration, respectively; 2), the probability per unit time of an MMP undergoing a ping-pong excursion increases monotonically with the field strength; and 3), the outward excursions exhibit a very unusual distance distribution which is dependent on the magnetic field strength. At any given field strength, a characteristic distance is observed, below which very few excursions occur. Beyond this distance, there is a rapid increase in the number of excursions with an exponentially decaying distribution. These observations cannot be explained by conventional magnetotaxis, i.e., a physical directing torque on the organism, and suggest a magnetoreceptive capability of the MMP.

Background Radiation↗

PubMed2004

A spatial statistical model for landscape genetics.

Landscape genetics is a new discipline that aims to provide information on how landscape and environmental features influence population genetic structure. The first key step of landscape genetics is the spatial detection and location of genetic discontinuities between populations. However, efficient methods for achieving this task are lacking. In this article, we first clarify what is conceptually involved in the spatial modeling of genetic data. Then we describe a Bayesian model implemented in a Markov chain Monte Carlo scheme that allows inference of the location of such genetic discontinuities from individual geo-referenced multilocus genotypes, without a priori knowledge on populational units and limits. In this method, the global set of sampled individuals is modeled as a spatial mixture of panmictic populations, and the spatial organization of populations is modeled through the colored Voronoi tessellation. In addition to spatially locating genetic discontinuities, the method quantifies the amount of spatial dependence in the data set, estimates the number of populations in the studied area, assigns individuals to their population of origin, and detects individual migrants between populations, while taking into account uncertainty on the location of sampled individuals. The performance of the method is evaluated through the analysis of simulated data sets. Results show good performances for standard data sets (e.g., 100 individuals genotyped at 10 loci with 10 alleles per locus), with high but also low levels of population differentiation (e.g., FST<0.05). The method is then applied to a set of 88 individuals of wolverines (Gulo gulo) sampled in the northwestern United States and genotyped at 10 microsatellites.

Animals↗

PubMed2006

Genomewide expression profiling in the zebrafish embryo identifies target genes regulated by Hedgehog signaling during vertebrate development.

Hedgehog proteins play critical roles in organizing the embryonic development of animals, largely through modulation of target gene expression. Little is currently known, however, about the kinds and numbers of genes whose expression is controlled, directly or indirectly, by Hedgehog activity. Using techniques to globally repress or activate Hedgehog signaling in zebrafish embryos followed by microarray-based expression profiling, we have discovered a cohort of genes whose expression responds significantly to loss or gain of Hedgehog function. We have confirmed the Hedgehog responsiveness of a representative set of these genes with whole-mount in situ hybridization as well as real time PCR. In addition, we show that the consensus Gli-binding motif is enriched within the putative regulatory elements of a sizeable proportion of genes that showed positive regulation in our assay, indicating that their expression is directly induced by Hedgehog. Finally, we provide evidence that the Hedgehog-dependent spatially restricted transcription of one such gene, nkx2.9, is indeed mediated by Gli1 through a single Gli recognition site located within an evolutionarily conserved enhancer fragment. Taken together, this study represents the first comprehensive survey of target genes regulated by the Hedgehog pathway during vertebrate development. Our data also demonstrate for the first time the functionality of the Gli-binding motif in the control of Hedgehog signaling-induced gene expression in the zebrafish embryo.

Animals↗

PubMed1997

[Characteristics of neonatal mortality in the State of Rio de Janeiro, Brazil, in the 1980's: a spatio-temporal analysis].

OBJECTIVE: The spatial distribution of neonatal mortality by age-group (0-23 hours, 1-6 days and 7-27 days) in the State of Rio de Janeiro, Brazil, for two periods of time 1979-81 and 1990-92, is analysed. METHODOLOGY: A methodology was used to perform the spatial analysis which took the counties of Rio de Janeiro as the spatial units and "first-nearest-neighbors" as the neighborhood criterion. For the purpose of detecting anisotropy, the connection matrix was defined through "first-nearest-neighbors" in a particular direction. To understand the spatial behavior of neonatal mortality, social and environmental indicators and indicators of medical assistance by county for both periods of time were constructed. RESULTS AND CONCLUSIONS: At the beginning of the 80's, the neonatal mortality for the age group 7-27 days showed the presence of clusters in the East and Southeast in direct association with the poorest conditions of life in the State, characteristics that had vanished by the next decade. Spatial dependence for the mortality rates for the first day of life, for 1991, was identified clusters in two different regions beings detected, followed by a positive correlation with "number of private hospital beds per inhabitant". Some of the cluster counties were, in particular, death receivers from neighboring counties and showed hospital case fatality rates much greater than the overall mean rate.

Anisotropy↗