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Role of thalamocortical sensory suppression during arousal: focusing sensory inputs in neocortex.

The thalamus serves as a gate that regulates the flow of sensory inputs to the neocortex, and this gate is controlled by neuromodulators from the brainstem reticular formation that are released during arousal. We found recently that sensory-evoked responses are suppressed in the neocortex during arousal. This sensory suppression results from the activity-dependent depression of the thalamocortical connection caused by increased tonic firing of thalamocortical cells during arousal. In the present study, the functional consequences of thalamocortical suppression during arousal were investigated using the vibrissae system of rodents. The results show that thalamocortical suppression is associated with a strong reduction in the spread of sensory inputs through the cortex, thus reducing the size of sensory representations. In addition, when the responses of single cells to principal and adjacent whiskers are compared, the response to the adjacent whiskers was found to be strongly suppressed, much more so than that of principal whiskers. Consequently, the receptive fields of cortical neurons become more focused to the principal whisker. The results indicate that thalamocortical suppression during arousal serves to focus sensory inputs to their appropriate representations in neocortex, which may be computationally helpful for the spatial processing of sensory information.

Animals↗

Actin and tropomyosin isoforms in morphogenesis.

The major components of the actin microfilament system, actin and tropomyosin (Tm), are encoded by multigene families. There are at least 6 actin and over 20 Tm isoforms in mammals. The observation that isoforms are expressed in a tissue-specific manner has encouraged the hypothesis that they contribute to the formation of cell type-specific structures. Recent studies have indicated that certain specific isoforms do play unique structural roles. One nonmuscle actin isoform, beta, is implicated in the regulation of cell spreading and membrane organisation. The intracellular location of beta-actin mRNA has been shown to be regulated by growth factor stimulation of signal transduction pathways. Actin isoforms have also been shown to differ in their contractile properties in both muscle and non-muscle cells. Tropomyosins have been found to show isoform specific regulation in response to cell transformation. This has correlated with the view that some isoforms of tropomyosin promote filament stability whereas others are associated with more dynamic structures. Neuronal development and maturation are accompanied by dynamic spatial sorting of tropomyosin isoforms into different cellular compartments. It is now apparent that isoforms of these proteins perform different structural tasks. The challenge is now to link the significance of spatial sorting to the different physicochemical properties of these isoforms.

Actin Cytoskeleton↗

Structural organization and chromosomal location of the chicken alpha-amylase gene family.

Characterization of the Gallus gallus alpha-amylase gene family revealed that the chicken genome contains two distinct amy loci. One of the two loci is expressed in the chicken pancreas while cDNA clones for the second locus were detected in a library constructed from liver mRNA. Fluorescent in situ hybridization to chromosome spreads showed that the two loci are both located on chromosome 8 within the chicken genome. Moreover, each locus contains both an intact, expressed gene copy as well as a pseudogene. The expressed gene and the pseudogene are arranged in a divergent configuration in the pancreatic amy locus, while in the hepatic locus the intact gene and the pseudogene are arranged in tandem. The data suggest a complex pattern of evolution for the chicken amylase gene family which includes multiple gene duplication events, insertion/deletion events, as well as changes in spatial expression patterns.

Amino Acid Sequence↗

Assessing the capabilities of a 4kx4k CCD camera for electron cryo-microscopy at 300kV.

CCD cameras have numerous advantages over photographic film for detecting electrons; however the point spread function of these cameras has not been sufficient for single particle data collection to subnanometer resolution with 300kV microscopes. We have adopted spectral signal to noise ratio (SNR) as a parameter for assessing detector quality for single particle imaging. The robustness of this parameter is confirmed under a variety of experimental conditions. Using this parameter, we demonstrate that the SNR of images of either amorphous carbon film or ice embedded virus particles collected on a new commercially available 4kx4k CCD camera are slightly better than photographic film at low spatial frequency (<1/5 Nyquist frequency), and as good as photographic film out to half of the Nyquist frequency. In addition it is slightly easier to visualize ice embedded particles on this CCD camera than on photographic film. Based on this analysis it is realistic to collect images containing subnanometer resolution data (6-9A) using this CCD camera at an effective magnification of approximately 112000x on a 300kV electron microscope.

Cryoelectron Microscopy↗

Retinotopic organisation of cortical mechanisms responsive to colour: evidence from patient studies.

This paper deals with the visual responses of three patients who have impaired colour vision consequent on cortical dysfunction which, in two of them, is associated with demonstrable neuronal damage. The studies to be described are concerned particularly with the spatial attributes of their chromatic response mechanisms. Data are presented which establish that a hemianope GY has coarse chromatic discrimination for large stimuli located within his 'blind' hemifield. GY responds to stimuli containing differently coloured equiluminant components as if the coloured components were averaged over the whole field and it is speculated that such spatial averaging may correspond to the process which, in normal vision, provides compensation for change of illuminant in order to achieve colour constancy. Colour constancy is impaired in a second patient, BL, who has cortical lesions involving the lingual and fusiform gyri, areas which are partially spared in GY. It is shown that movement, but not colour, presented to GY's normal hemifield generates a response localised in his blind hemifield and disinhibitory interaction between movement and colour is illustrated for a patient MW, in whom colour chromatic stimuli generate spreading inhibition of visual responses. This inhibitory interaction is propagated between widely separated stimuli, including those which are located on opposite sides of the vertical meridian. We discuss these experimental results in relation to anatomical and physiological mechanisms of the primate visual cortex.

Adult↗

High fidelity functional patterns of an extracellular matrix protein by electron beam-based inactivation.

Controlling the organization of proteins on surfaces provides a powerful biochemical tool for determining how cells interpret the spatial distribution of local signaling molecules. Here, we describe a general high fidelity approach based on electron beam writing to pattern the functional properties of protein-coated surfaces at length scales ranging from tens of nanometers to millimeters. A silicon substrate is first coated with the extracellular matrix protein fibronectin, which is then locally inactivated by exposure to a highly focused electron beam. Biochemical inactivation of the protein is established by the loss of antibody binding to the fibronectin. Functional inactivation is determined by the inability of cells to spread or form focal adhesions on the inactivated substrate, resulting in cell shapes constrained to the pattern, while they do both (and are unconstrained) on the remaining fibronectin. These protein patterns have very high fidelity, and typical patterns agree with the input dimensions of the pattern to within 2%. Further, the feature edges are well defined and approach molecular dimensions in roughness. Inactivation is shown to be dose dependent with observable suppression of the specific binding at 2 microC cm(-2) and complete removal of biochemical activity at approximately 50 microC cm(-2) for 5 keV electrons. The critical dose for inactivation also depends on accelerating voltage, and complete loss of antibody binding was achieved at approximately 4-7 microC cm(-2) for 1 keV electrons, which corresponds to approximately 50-90 electrons per cross-sectional area of a whole fibronectin dimer and ~2-4 electrons per type III fibronectin domain. AFM analysis of the pattern surfaces revealed that electron beam exposure does not remove appreciable amounts of material from the surface, suggesting that the patterning mechanism involves local inactivation rather than the ablation that has been observed in several organic thin film systems.

Animals↗

Properties of surface and junctional membranes of embryonic cells isolated from blastula stages of Xenopus laevis.

1. Some membrane properties of endoderm and mesoderm cells isolated from late blastula stages of Xenopus laevis have been examined using electrophysiological techniques. 2. Cells were isolated by treatment of whole embryos with Ca-free EDTA containing media, or mechanically by micro-dissection, and cultured in Ca-containing Holtfreter solution (60 mM-NaCl) or Ringer solution (120 mM-NaCl). 3. Membrane potentials lay between -6 and -84 mV; specific membrane resistances ranged from 500 to 29,000 omega cm2; there was no difference between EDTA isolated and mechanically isolated cells. 4. Relative and absolute cation and anion conductances varied from cell to cell. Some cells were anion impermeable; the cation conductance ranged from 35 to 300 mumho/cm2. 5. The resting potential of some cells was largely determined by the concentration gradient and membrane permeability of K ions. In other cells the potential was maintained either by some other ion or by an electrogenic pump. [K]i came to approximately 130 mM in Ringer solution (the value pertaining in the intact embryo) and similar to 60 mM in Holtfreter solution. 6. In most pairs and small clumps of cells ionic current spread from one cell to the next; some single cells and groups of cells were uncoupled from their neighbours. 7. The junctional resistance lay between 10(5) and 10(8) omega; it behaved as a linear resistor in most cell pairs studied. In three pairs the intercellular junction showed rectifying properites. 8. By the late blastula stage of development presumptive endoderm and mesoderm cells form a heterogeneous population with widely varying passive membrane properties. The significance of these findings is discussed in relation to current hypotheses for the formation of spatial patterns during differentiation.

Animals↗

Activity-dependent changes in intracellular calcium in myenteric neurons.

The spatial distribution and changes in intracellular calcium concentration ([Ca2+]i) in myenteric neurons were measured using fura 2 in the longitudinal muscle-myenteric plexus preparation from the guinea pig duodenum. These measurements were made simultaneously with intracellular voltage recordings. The generation of action potentials in the cell bodies of both S- and AH-type neurons increased [Ca2+]i in the processes and cell bodies. There was no measurable delay between the [Ca2+]i changes in the somata and the processes, indicating that these changes were caused by the spread of electrical signals and not by diffusion. The rate of Ca2+ removal was faster in the processes than in the somata, apparently due to the large surface-to-volume ratio in the former. In AH neurons, the [Ca2+]i transient was shorter than the duration of the after-spike hyperpolarization. It is concluded that the two main types of myenteric neurons possess voltage-gated Ca2+ channels in both somata and processes.

Action Potentials↗

[Dutch residents of Indonesian origin, January 1, 1990].

Data on persons of Indonesian origin living in the Netherlands as of January 1, 1990, are presented. As of that date 473,000 persons of Indonesian origin lived in the country and of those "only 8 thousand were Indonesian nationals. About 57%...was born in the Netherlands, thus belonging to the second generation.... The sex-ratio in the population of Indonesian origin is about 1 and corresponds to that of the Dutch population. Slight differences appear in the age composition and marital status of the population. The mean age of the Dutch population is about 36.6, whereas the Indonesian population is on average 35.3 years old.... The Indonesian population is less often married than the population of the Netherlands as a whole and slightly more often never married, or divorced.... The Indonesian population lives rather evenly spread over the country." (SUMMARY IN ENG)

Age Distribution↗

High-resolution ultrasonic imaging using fast two-dimensional homomorphic filtering.

A new method for two-dimensional deconvolution of medical ultrasonic images is presented. The spatial resolution of the deconvolved images is much higher compared to the common images of the fundamental and second harmonic. The deconvolution also results in a more distinct speckle pattern. Unlike the most published deconvolution algorithms for ultrasonic images, the presented technique can be implemented using currently available hardware in real-time imaging, with a rate up to 50 frames per second. This makes it attractive for application in the current ultrasound scanners. The algorithm is based on two-dimensional homomorphic deconvolution with simplified assumptions about the point spread function. Broadband radio frequency image data are deconvolved instead of common fundamental harmonic data. Thus, information of both the first and second harmonics is used. The method was validated on image data recorded from a tissue-mimicking phantom and on clinical image data.

Algorithms↗

Mussel disturbance dynamics: signatures of oceanographic forcing from local interactions.

Local interactions, biotic and abiotic, can have a strong influence on the large-scale properties of ecosystems. However, ecological models often explore the influence of local biotic interactions where physical disturbance is included as a large-scale and imposed source of variability but is not allowed to interact with biotic processes at the local scale. In marine intertidal communities dominated by mussels, wave disturbances create gaps in the mussel bed that recover through a successional sequence. We present a lattice model of mussel disturbance dynamics that allows local interactions between wave disturbance and mussel recolonization, in which each cell of the lattice can be empty, occupied by a mussel bed element, or disturbed (which corresponds to a newly disturbed cell that has unstable edges). As in natural ecosystems, wave disturbance can also spread from disturbed to adjacent occupied cells, and recolonization can also spread from occupied to adjacent empty cells. We first validate the local rules from artificial gap experiments and from natural gap monitoring along the Oregon coast. We analyze the properties of the model system as a function of different oceanographic forcings of productivity and disturbance. We show that the mussel bed can go through phase transitions characterized by a large sensitivity of mussel cover and patterns to oceanographic forcings but also that criticality (scale invariance) is observed over wide ranges of parameters, which suggests self-organization. We also show that spatial patterns in the intertidal can provide a robust signature of local processes and can inform about oceanographic regimes. We do so by comparing the large-scale patterns of the simulation (scaling exponents) with field data, which suggest that some experimental sites are close to criticality. Our results suggest that regional patterns in disturbed populations can be explained by local biotic and abiotic processes submitted to oceanographic forcing.

Animals↗

Changes in cell shape and desmin intermediate filament distribution are associated with down-regulation of desmin expression in C2C12 myoblasts grown in the absence of extracellular Ca2+.

Desmin is the main intermediate filament (IF) protein of muscle cells. In skeletal muscle, desmin IFs form a scaffold that interconnects the entire contractile apparatus with the subsarcolemmal cytoskeleton and cytoplasmic organelles. The interaction between desmin and the sarcolemma is mediated by a number of membrane proteins, many of which are Ca2+-sensitive. In the present study, we analyzed the effects of the Ca2+ chelator EGTA (1.75 mM) on the expression and distribution of desmin in C2C12 myoblasts grown in culture. We used indirect immunofluorescence microscopy and reverse transcription polymerase chain reaction (RT-PCR) to analyze desmin distribution and expression in C2C12 cells grown in the presence or absence of EGTA. Control C2C12 myoblasts showed a well-spread morphology after a few hours in culture and became bipolar when grown for 24 h in the presence of EGTA. Control C2C12 cells showed a dense network of desmin from the perinuclear region to the cell periphery, whereas EGTA-treated cells showed desmin aggregates in the cytoplasm. RT-PCR analysis revealed a down-regulation of desmin expression in EGTA-treated C2C12 cells compared to untreated cells. The present results suggest that extracellular Ca2+ availability plays a role in the regulation of desmin expression and in the spatial distribution of desmin IFs in myoblasts, and is involved in the generation and maintenance of myoblast cell shape.

Animals↗

Population dynamics and theta rhythm phase precession of hippocampal place cell firing: a spiking neuron model.

O'Keefe and Recce ([1993] Hippocampus 68:317-330) have observed that the spatially selective firing of pyramidal cells in the CA1 field of the rat hippocampus tends to advance to earlier phases of the electroencephalogram theta rhythm as a rat passes through the place field of a cell. We present here a neural network model based on integrate- and-fire neurons that accounts for this effect. In this model, place selectivity in the hippocampus is a consequence of synaptic interactions between pyramidal neurons together with weakly selective external input. The phase shift of neuronal spiking arises in the model as result of asymmetric spread of activation through the network, caused by asymmetry in the synaptic interactions. Several experimentally observed properties of the phase shift effect follow naturally from the model, including 1) the observation that the first spikes a cell fires appear near the theta phase corresponding to minimal population activity, 2) the overall advance is less than 360 degrees, and 3) the location of the rat within the place field of the cell is the primary correlate of the firing phase, not the time the rat has been in the field. The model makes several predictions concerning the emergence of place fields during the earliest stages of exploration in a novel environment. It also suggests new experiments that could provide further constraints on a possible explanation of the phase precession effect.

Animals↗

Innervation from the claustrum of the frontal association and motor areas: axonal transport studies in the cat.

The anatomical organization of the projections from the claustrum to the motor and prefrontal cortical areas of the cat's brain was investigated. Both retrograde (single horseradish peroxidase or double fluorochrome deposits in the cortex) and anterograde (peroxidase-labeled wheat germ agglutinin deposits in the claustrum) tracing techniques were used. Within the claustrum, the neurons projecting to each sector of the frontal cortex were found to be distributed according to specific patterns of segregation and overlap. Spatial segregation was particularly marked between the cell populations projecting to the various sectors of area 4. The cells projecting to the subareas of area 6 and prefrontal cortex displayed a less marked but definite segregation. The neuronal populations projecting to some sectors of areas 4, 5, and the primary somatosensory cortex known to contain homotopical representations of the body map were found intermingled in the same small claustral portions. The few double-labeled neurons found after closely adjacent fluorochrome injections indicates that, in spite of their profuse intracortical branching, claustral axons spread little within the boundaries of a single architectonic area. Anterograde transport experiments showed that claustral fibers end primarily in layers IIIb/IV, VI, and I, whereas layer V is spared. This pattern is homogeneous throughout the frontal cortex. The possible role of the claustrum as a subcortical site for organized interactions amongst wide arrays of functionally related zones of the cerebral cortex is thereby suggested.

Animals↗

Single-shot half k-space high-resolution gradient-recalled EPI for fMRI at 3 Tesla.

Half k-space gradient-recalled echo-planar imaging (GR-EPI) is discussed in detail. T2* decay during full k-space GR-EPI gives rise to unequal weighting of the lines of k-space, loss of signal intensity at the center of k-space, and a point-spread function that limits resolution. In addition, the long readout time for high-resolution full k-space acquisition gives rise to severe susceptibility effects. These problems are substantially reduced by acquiring only half of k-space and filling the empty side by Hermitian conjugate formation. Details of the pulse sequence and image reconstruction are presented. The point-spread function is 3(1/2) times narrower for half than full k-space acquisition. Experiments as well as theoretical considerations were carried out in a context of fMRI using a whole-brain local gradient and an RF coil at 3 Tesla. Using a bandwidth of +/-83 kHz, well-resolved single-shot images of the human brain, as well as good quality fMRI data sets were obtained with a matrix of 192 x 192 over 16 x 16 cm2 FOV using half k-space techniques. The combination of high spatial resolution using the methods presented in this article and the high temporal resolution of EPI opens opportunities for research into fMRI contrast mechanisms. Increase of percent signal change as the resolution increases is attributed to reduction of partial volume effects of activated voxels. Histograms of fMRI pixel responses are progressively weighted to higher percent signal changes as the resolution increases. The conclusion has been reached that half k-space GR-EPI is generally superior to full k-space GR-EPI and should be used even for low-resolution (64 x 64) EPI.

Brain↗

Space and stochasticity in population dynamics.

Organisms interact with each other mostly over local scales, so the local density experienced by an individual is of greater importance than the mean density in a population. This simple observation poses a tremendous challenge to theoretical ecology, and because nonlinear stochastic and spatial models cannot be solved exactly, much effort has been spent in seeking effective approximations. Several authors have observed that spatial population systems behave like deterministic nonspatial systems if dispersal averages the dynamics over a sufficiently large scale. We exploit this fact to develop an exact series expansion, which allows one to derive approximations of stochastic individual-based models without resorting to heuristic assumptions. Our approach makes it possible to calculate the corrections to mean-field models in the limit where the interaction range is large, and it provides insight into the performance of moment closure methods. With this approach, we demonstrate how the buildup of spatiotemporal correlations slows down the spread of an invasion, prolongs time lags associated with extinction debt, and leads to locally oscillating but globally stable coexistence of a host and a parasite.

Biological Evolution↗

The CT's sample volume as an approximate, instrumental measure for density resolution in densitometry of the lung.

Ultimately CT-densitometry of the lung should give comparable results on all scanners. One prerequisite for this is the use of the same density resolution. Unfortunately, density resolution is impractical as a performance specifying parameter because it depends on the cellular material scanned. Therefore, another parameter that can be used for scanner and protocol characterization, and that does not depend on a special phantom, would be highly preferable. We investigated how well the CT's nominal sample volume (V), calculated from section thickness and in-plane spatial resolution as specified by the CT manufacturer, can serve as a simple measure, for density resolution. Six CT scanners were studied using foam and lung phantoms. On all scanners we observed for foam an approximately linear relation between density resolution and V-1/2. Density resolution on different scanners varied to some extent. These differences can be interpreted as being caused by deviations of the true sample volume from the nominal value: the 95%-confidence interval runs for instance for V = 8 mm3 from 4.6 mm3 to 16.9 mm3. Acceptability of this spread depends on the consequences for parameters of clinical interest, like percentiles and pixel indexes. To evaluate this we used data from a previous patient study on the dependence of histogram parameters on sample volume. With these data it is found that large interscanner differences in histogram parameters are possible for small values of V, as used in thin-section densitometry. For larger values of V, as required for a more adequate density resolution, the differences are much smaller and probably acceptable when compared to other sources of variability in lung densitometry. In conclusion, for sections of at least 2 mm and smooth reconstruction filters, corresponding to V > or = 8 mm3, the CT's nominal sample volume might be used for interscanner and interprotocol comparison of density resolution.

Absorptiometry, Photon↗

The spatial dynamics of prion disease.

An important component of the latency period of the transmissible spongiform encephalopathies (prion diseases) can be attributed to delays during the propagation of the infectious prion isoform, PrPSc, through peripheral nervous tissues. A growing body of data report that the host prion protein, PrPC, is required in both peripheral and central nervous tissues for susceptibility to infection. We introduce a mathematical model, which treats the PrPSc as a mobile infectious pathogen, and show how peripheral delays can be understood in terms of the intercellular dispersal properties of the PrPSc strain, its decay rate, and its efficiency at transforming the PrPC. It has been observed that when two pathogenic strains co-infect a host, the presence of the first inoculated strain can slow down, or stop completely, the spread of the second strain. This is thought to result from a reduced concentration of host protein available for conversion by the second strain. Our model can explain the mechanisms of such interstrain competition and the time-course of the increased delay. The model provides a link between those data suggesting a role for a continuous chain of PrP-expressing tissue linking peripheral sites to the brain, and data on prion strain competition.

Animals↗