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PubMed2000

Transcranial magnetic stimulation in cognitive neuroscience--virtual lesion, chronometry, and functional connectivity.

Fifteen years after its introduction by Anthony Barker, transcranial magnetic stimulation (TMS) appears to be 'coming of age' in cognitive neuroscience and promises to reshape the way we investigate brain-behavior relations. Among the many methods now available for imaging the activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with brain function. As illustrated by several experiments over the past couple of years, this property of TMS allows us to investigate the relationship between focal cortical activity and behavior, to trace the timing at which activity in a particular cortical region contributes to a given task, and to map the functional connectivity between brain regions.

Behavior↗
PubMedDate not supplied

Mapping by monoclonal antibody detection of glycosaminoglycans in connective tissues.

Chondroitin sulphate proteoglycans are widespread connective tissue components and chemical analysis of cartilage and other proteoglycans has demonstrated molecular speciation involving the degree and position of sulphation of the carbohydrate chains. This may, in turn, affect the properties of the glycosaminoglycan (GAG), particularly with respect to self-association and interactions with other extracellular matrix components. Interactions with specific molecules from different connective tissue types, such as the collagens and their associated glycoproteins, could be favoured by particular charge organizations on the GAG molecule endowed by the sulphate groups. So far, it has not been possible to identify and map chondroitins of differing sulphation in tissues, but we have now raised three monoclonal antibodies which specifically recognize unsulphated, 4-sulphated and 6-sulphated chondroitin and dermatan sulphate. These provide novel opportunities to study the in vivo distribution of chondroitin sulphate proteoglycans. We demonstrate that chondroitin sulphates exhibit remarkable connective tissue specificity and furthermore provide evidence that some proteoglycans may predominantly carry only one type of chondroitin sulphate chain.

Animals↗
PubMed2004

Intrinsic connections in tree shrew V1 imply a global to local mapping.

The local-global map hypothesis states that locally organized response properties--such as orientation preference--result from visuotopically organized local maps of non-retinotopic response properties. In the tree shrew, the lateral extent of horizontal patchy connections is as much as 80-100% of V1 and is consistent with the length summation property. We argue that neural signals can be transmitted across the entire extent of V1 and this allows the formation of maps at the local scale that are visuotopically organized. We describe mechanisms relevant to the formation of local maps and report modeling results showing the same patterns of horizontal connectivity, and relationships to orientation preference, seen in vivo. The structure of the connectivity that emerges in the simulations reveals a 'hub and spoke' organization. Singularities form the centers of local maps, and linear zones and saddle-points arise as smooth border transitions between maps. These findings are used to present the case for the local-global map hypothesis for tree shrew V1.

Animals↗
PubMed1995

Subdivisions of macaque monkey auditory cortex revealed by calcium-binding protein immunoreactivity.

The aim of this investigation was to characterize auditory areas of the primate cerebral cortex on the basis of chemoarchitecture. Cortical areas of the supratemporal plane were delineated in Macaca fuscata (M. fuscata) by immunocytochemical staining for parvalbumin, staining for cytochrome oxidase, examination of cyto- and myeloarchitecture, and retrograde tracing of corticocortical connections. Comparative observations were made on Macaca fascicularis (M. fascicularis). Differential staining of fiber plexuses, probably of thalamic origin, identifies a central core zone of dense immunostaining and a surrounding zone of moderate-to-dense immunostaining composed of anteromedial, lateral, and posteromedial fields. Outside the second zone, there is a third anterolateral zone of weaker immunoreactivity, and, outside that zone, there is a fourth zone in which immunoreactivity is virtually absent. Differences in parvalbumin immunostaining in the auditory fields may reflect differences in relative contributions of thalamic inputs from parvalbumin-immunoreactive cells in the medial geniculate complex. The central core zone and the surrounding three fields can be correlated with major auditory fields previously defined by multiunit mapping and thalamocortical connectivity. The core zone contains a large principal field and an anterior extension. The pattern of corticocortical connections between these and adjoining fields suggests that the anteromedial, lateral, and posteromedial fields represent first steps in three streams of connections passing outward from auditory into association cortex. M. fuscata has an unusually large auditory cortex that is more deeply placed in the lateral sulcus in comparison to that of M. fascicularis. A small annectant gyrus provides a guide to the position of the primary auditory area.

Animals↗
PubMed1990

Solution structural characteristics of cyanometmyoglobin: resonance assignment of heme cavity residues by two-dimensional NMR.

Steady-state nuclear Overhauser effects (NOE), two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY), and 2D spin correlation spectroscopy (COSY) have been applied to the fully paramagnetic low-spin, cyanide-ligated complex of sperm whale ferric myoglobin to assign the majority of the heme pocket side-chain proton signals and the remainder of the heme signals. It is shown that the 2D NOESY map reveals essentially all dipolar connectivities observed in ordinary 1D NOE experiments and expected on the basis of crystal coordinates, albeit often more weakly than in a diamagnetic analogue. For extremely broad (approximately 600-Hz) and rapidly relaxing (Tf1 approximately 3 ms) signals which show no NEOSY peaks, we demonstrate that conventional steady-state NOEs obtained under very rapid pulsing conditions still allow detection of the critical dipoar connectivities that allow unambiguous assignments. The COSY map was found to be generally less useful for the hyperfine-shifted residues, with cross peaks detected only for protons greater than 6 A from the iron. Nevertheless, numerous critical COSY cross peaks between strongly hyperfine-shifted peaks were resolved and assigned. In all, 95% (53 of 56 signals) of the total proton sets within approximately 7.5 A of the iron, the region experiencing the strongest hyperfine shifts and paramagnetic relaxation, are now unambiguously assigned. Hence it is clear that the 2D methods can be profitably applied to paramagnetic proteins. The scope and limitations of such application are discussed. The resulting hyperfine shift pattern for the heme confirmed expectations based on model compounds. In contrast, while exhibiting fortuitous 1H NMR spectral similarities, a major discrepancy was uncovered between the hyperfine shift pattern of the axially bound (F8 histidyl) imidazole in the protein and that of the imidazole in a relevant model compound [Chacko, V.P., & La Mar, G. N. (1982) J. Am. Chem. Soc. 104, 7002-7007], providing direct evidence for a protein-based deformation of axial bonding in the protein.

Amino Acids↗
PubMed2006

Prediction of yeast protein-protein interaction network: insights from the Gene Ontology and annotations.

A map of protein-protein interactions provides valuable insight into the cellular function and machinery of a proteome. By measuring the similarity between two Gene Ontology (GO) terms with a relative specificity semantic relation, here, we proposed a new method of reconstructing a yeast protein-protein interaction map that is solely based on the GO annotations. The method was validated using high-quality interaction datasets for its effectiveness. Based on a Z-score analysis, a positive dataset and a negative dataset for protein-protein interactions were derived. Moreover, a gold standard positive (GSP) dataset with the highest level of confidence that covered 78% of the high-quality interaction dataset and a gold standard negative (GSN) dataset with the lowest level of confidence were derived. In addition, we assessed four high-throughput experimental interaction datasets using the positives and the negatives as well as GSPs and GSNs. Our predicted network reconstructed from GSPs consists of 40,753 interactions among 2259 proteins, and forms 16 connected components. We mapped all of the MIPS complexes except for homodimers onto the predicted network. As a result, approximately 35% of complexes were identified interconnected. For seven complexes, we also identified some nonmember proteins that may be functionally related to the complexes concerned. This analysis is expected to provide a new approach for predicting the protein-protein interaction maps from other completely sequenced genomes with high-quality GO-based annotations.

Databases, Genetic↗
PubMed2006

Selective spread of neurotropic herpesviruses in the rat hippocampus.

Transsynaptically spreading viruses are widely used for tracing neuronal circuits in both the central and peripheral nervous systems. However, viruses are capricious tools with selective spreading properties that can produce false-negative results. Using herpes simplex virus type 1 and two pseudorabies virus strains, we aimed at mapping quantitatively neuronal connections in the rat hippocampus. We found that none of the tested viruses infected CA3 pyramidal neurons across synapses following inoculation into the CA1 area. Combined injections of the viruses with the retrograde tracer cholera toxin B (CTB) resulted in CTB, but not virus labeling of CA3 pyramidal neurons. In contrast, other brain regions known to send inputs to the CA1 (the entorhinal cortex, medial septum and diagonal band of Broca, raphe nuclei) were transsynaptically infected. Our results indicate that Schaffer collaterals of CA3 pyramidal cells lack the appropriate cellular machinery for successful neurotropic herpesvirus infection. After injections of viruses into the dentate gyrus/CA3 area, we found labeling in commissurally projecting mossy cells and their afferent granule cells but not in contralateral CA3 pyramidal cells. Using this unique spreading property, we estimated that single mossy cells receive input from a compact cluster of 30-40 granule cells.

Animals↗
PubMed2003

Positron emission tomography during transcranial magnetic stimulation does not require mu-metal shielding.

Recording brain activity using positron emission tomography (PET) during the stimulation of different parts of the brain by transcranial magnetic stimulation (TMS) permits the mapping of neural connections in the living human brain. However, controversy remains regarding the need for micro-metal shielding of the PET scanner during magnetic stimulation. The aim of this study was to test the effects of magnetic fields generated by TMS on PET data acquisition. With TMS-on and -off in the PET field of view, transmission scans with a (68)Ge/(68)Ga pin source and emission scans with an uniform phantom filled with water and (18)F were acquired. The frequency and intensity of stimulation were set at 3-5 Hz and 70-80% of the maximum output of the stimulator, respectively. The TMS coil was placed at several locations inside the PET gantry, and the main field direction of the TMS coil was varied between parallel and perpendicular orientation to the scanner's axis. Qualitative and quantitative evaluation of the sinograms of transmission PET scans and reconstructed emission images indicated no measurable differences between TMS-on and -off and post-TMS conditions for any position or orientation. The long distance between the TMS coil and the detector block in the PET scanner, as well as the rapid reduction of the magnetic field with distance (3% of maximum field at 10 cm, in air), could explain the lack of TMS interference. The brief duration (approximately 250 micros) of the TMS pulses relative to the total PET acquisition time would also explain the lack of TMS effects. The lack of TMS effects on the PET scanner, as well as PET imaging without any shielding, has been reported by other laboratories.

Brain↗
PubMed2004

Regulation of connective tissue growth factor (CTGF/CCN2) gene transcription and mRNA stability in smooth muscle cells. Involvement of RhoA GTPase and p38 MAP kinase and sensitivity to actin dynamics.

Connective tissue growth factor (CTGF/CCN2) is an immediate early gene-encoded polypeptide modulating cell growth and collagen synthesis. The importance of CTGF/CCN2 function is highlighted by its disregulation in fibrotic disorders. In this study, we investigated the regulation and signaling pathways that are required for various stimuli of intracellular signaling events to induce the expression of the endogenous CTGF/CCN2 gene in smooth muscle cells. Incubation with the bioactive lysolipid sphingosine 1-phosphate (S1P) produced a threefold increase, whereas stimulation with either fetal bovine serum or anisomycin induced an even stronger activation (eightfold) of CTGF/CCN2 expression. Using a combination of pathway-specific inhibitors and mutant forms of signaling molecules, we found that S1P- and fetal bovine serum-induced CTGF/CCN2 expression were dependent on both RhoA GTPase and p38 mitogen-activated protein kinase transduction pathways, whereas the effects of anisomycin largely involved p38 and phosphatidyl inositol 3-kinase signaling mechanisms. However, activation via these signaling events was absolutely dependent on actin cytoskeleton integrity. In particular, RhoA-dependent regulation of the CTGF/CCN2 gene was concomitant to increased polymerization of actin microfilaments resulting in decreased G- to F-actin ratio and appeared to be achieved at the transcriptional level. The p38 signaling pathway was RhoA-independent and led to CTGF/CCN2 mRNA stabilization. Use of actin-binding drugs showed that the actual physical state of monomeric G-actin is a critical determinant for CTGF/CCN2 gene induction. These data indicate that distinct cytoskeletally based signaling events within the intracellular signaling machinery affect either transcriptionally or post-transcriptionally the expression of the CTGF/CCN2 gene in smooth muscle cells.

Actins↗
PubMed1995

Refinement of the high-resolution physical and genetic map of Rhodobacter capsulatus and genome surveys using blots of the cosmid encyclopedia.

Cosmids from a library containing Rhodobacter capsulatus DNA fragments were previously ordered in two contigs: one corresponding to the chromosome and one to a 134 kb plasmid. This map contained 40 regions connected only by colony hybridization. To confirm the linkage and correct the map, the actual sizes of the overlaps were determined by blot-hybridization with Rhodobacter chromosomal DNA and by mapping of additional cosmids. Several revisions of the earlier map include single cosmid shifts and inversions. One additional gap in a cosmid contig was also found, raising the possibility that the chromosome is not a contiguous circle. About 2500 additional EcoRI,BamHI and HindIII restriction sites were added to the 560 EcoRV sites previously mapped onto the Rhodobacter chromosome, increasing the resolution of the physical map to the size of individual genes. Twenty-five new markers were located on the genetic map. The 48 markers now mapped represent nearly 300 genes and ORFs cloned from different species of Rhodobacter. The orientation of transcription of the four rrn operons was established using 16S rRNA- and 23S rRNA-specific probes and digestion with the rare-cutting enzyme, CeuI. Gel blots of 192 cosmids of the miniset of R.capsulatus digested with EcoRV were prepared. Such a hybridization template represents the whole genome cut into 560 DNA fragments varying in size from 0.4 to 25 kb. This template was used for high-resolution mapping of single genes, analysis of total genomic DNAs from related Rhodobacter strains and differentially expressed RNAs.

Chromosome Mapping↗
PubMed1997

[10 years radiofrequency ablation of accessory conduction pathways].

Catheter ablation of the preexcitation syndrome is a curative treatment. Accessory pathways between structures of the specific conduction system or working myocardium are morphologic prerequisites for orthodromic or antidromic reentrant tachycardia of various frequency, duration, and rate. Detection of mechanisms of tachyarrhythmias and understanding the role of accessory pathways in tachycardia, mapping of accessory connections, function of nodal conduction system, and additional accessory pathways are necessary for successful catheter ablation. Anomalies of the tricuspid valve and coronary sinus and concomitant disease of the heart should be investigated prior to catheter ablation using echocardiography and contrast injection. Different variations of the preexcitation syndrome and the results of catheter ablation in 300 patients are demonstrated. Catheter ablation is indicated in refractory tachyarrhythmias on the basis of accessory pathways. The treatment is performed in a catheterization laboratory by two highly experienced cardiologists in the field of electrophysiology after training in 100 procedures. The investigators need experience in interventional treatment of coronary artery disease, in transseptal puncture, and in the management of complications (coronary and valvular problems, thromboemboly, and pericardial drainage). Catheterization needs careful protection of radiation. An ablation is possible at an atrial or ventricular insertion site of the accessory pathway or in between. Ablation is done during sinus rhythm, atrial stimulation, antidromic reentry, or atrial fibrillation or during ventricular pacing and orthodromic tachycardia. The procedure should end with bidirectional block of the accessory pathway in 90-95% of the patients. Complications occur in 2-4% of procedures. Recovery of accessory conduction is observed in 8%. Catheter ablation of the accessory pathway is the treatment of first choice in symptomatic patients with the pre-excitation syndrome. The procedure has limited risks and a high success rate.

Cardiac Pacing, Artificial↗
PubMed2006

Follow your nose: axon pathfinding in olfactory map formation.

Two new studies report how discrete identities of olfactory sensory neurons are converted into a spatial map of axonal connections (Imai et al., 2006; Serizawa et al., 2006). They find that levels of cAMP signals derived from olfactory receptors (ORs) can direct targeting of axons along an axis, and that ORs and neural activity regulate expression of adhesion/guidance molecules in mosaic patterns that can sort axons into discrete locations.

Animals↗
PubMed2005

A web-based multimedia spatial information system to document Aedes aegypti breeding sites and dengue fever risk along the US-Mexico border.

This paper describes a web-based multimedia spatial information system used to support a study of the re-invasion of Aedes aegypti, the mosquito vector for dengue fever, in the deserts of the southwest United States/northwest Mexico. The system was developed applying Open Geospatial Consortium and World Wide Web Consortium Open Specifications and using Open Source Software. The system creates a sensory-rich environment, one which allows users to interact with the system to explore connections among data (maps, remotely sensed images, text, graphs, 360 degree panoramas and photos), visualize information, formulate their own interpretations, generate hypotheses and reach their own conclusions.

Animals↗
PubMedDate not supplied

Early lexical development in a self-organizing neural network.

In this paper we present a self-organizing neural network model of early lexical development called DevLex. The network consists of two self-organizing maps (a growing semantic map and a growing phonological map) that are connected via associative links trained by Hebbian learning. The model captures a number of important phenomena that occur in early lexical acquisition by children, as it allows for the representation of a dynamically changing linguistic environment in language learning. In our simulations, DevLex develops topographically organized representations for linguistic categories over time, models lexical confusion as a function of word density and semantic similarity, and shows age-of-acquisition effects in the course of learning a growing lexicon. These results match up with patterns from empirical research on lexical development, and have significant implications for models of language acquisition based on self-organizing neural networks.

Artificial Intelligence↗
PubMed2005

Central autonomic control of the bone marrow: multisynaptic tract tracing by recombinant pseudorabies virus.

Bone marrow is the primary place of hematopoiesis, where the development, survival and release of multipotent stem cells, progenitors, precursors and mature cells are under continuous humoral and neural control. Dense network of nerve fibers, containing various neurotransmitters is found in the bone marrow, however, the central neuronal circuit that regulates the activities of the bone marrow through these fibers remained unexplored. Transsynaptically connected neurons were mapped by virus-based transneuronal tracing technique using two isogenic, genetically engineered pseudorabies viruses, Bartha-DupGreen and Ba-DupLac expressing green fluorescent protein and beta-galactosidase, respectively. Bartha-DupGreen was injected into the femoral bone marrow of male rats and the progression of infection was followed 4-7 days post-inoculation. Virus-labeled cells were revealed in ganglia of the paravertebral chain and in the intermediolateral cell column of the lower thoracic spinal cord. Neurons were retrogradely labeled in the C1, A5, A7 catecholaminergic cell groups and several other nuclei of the ventrolateral and ventromedial medulla, the periaqueductal gray matter, the paraventricular and other hypothalamic nuclei, and in the insular and piriform cortex. Nerve transections and double-virus tracing from the bone marrow and the surrounding muscles were used to confirm the specific spreading of the virus. These results provide anatomical evidence for the CNS control of the bone marrow and identify putative brain areas, which are involved in autonomic regulation of the hematopoiesis, the release of progenitor cells, the blood supply and the immune cell function in the bone marrow.

Animals↗
PubMed2005

Spontaneous patterned retinal activity and the refinement of retinal projections.

A characteristic feature of sensory circuits is the existence of orderly connections that represent maps of sensory space. A major research focus in developmental neurobiology is to elucidate the relative contributions of neural activity and guidance molecules in sensory map formation. Two model systems for addressing map formation are the retinotopic map formed by retinal projections to the superior colliculus (SC) (or its non-mammalian homolog, the optic tectum (OT)), and the eye-specific map formed by retinal projections to the lateral geniculate nucleus of the thalamus. In mammals, a substantial portion of retinotopic and eye-specific refinement of retinal axons occurs before vision is possible, but at a time when there is a robust, patterned spontaneous retinal activity called retinal waves. Though complete blockade of retinal activity disrupts normal map refinement, attempts at more refined perturbations, such as pharmacological and genetic manipulations that alter features of retinal waves critical for map refinement, remain controversial. Here we review: (1) the mechanisms that underlie the generation of retinal waves; (2) recent experiments that have investigated a role for guidance molecules and retinal activity in map refinement; and (3) experiments that have implicated various signaling cascades, both in retinal ganglion cells (RGCs) and their post-synaptic targets, in map refinement. It is likely that an understanding of retinal activity, guidance molecules, downstream signaling cascades, and the interactions between these biological systems will be critical to elucidating the mechanisms of sensory map formation.

Animals↗
PubMedDate not supplied

Topological aspects of axonal regeneration.

The fibers making up any sensory system in the spinal cord come from the same cells as do the fibers in peripheral nerves yet severed nerve fibers in the adult spinal cord do not regenerate but damaged peripheral nerves - those in the extremities - do heal themselves. Why should spinal cord regeneration even be an issue, why should an inhibiting protein have evolved to prevent it and what causes this protein to be expressed? From a holistic perspective, an answer to this conundrum shows that these questions are intertwined, and suggests that: (1) The model of the neurons as 'wires' is too simplistic. (2) In humans, the 'map' of individual connections is (topologically, at least) locally variable, though the overall global topology and 'functionality' of each normal spinal cord is constant. Both of these issues have to be addressed if functional restoration is to be achieved.

Animals↗
PubMed1999

Chordate origins of the vertebrate central nervous system.

Fine structural, computerized three-dimensional (3D) mapping of cell connectivity in the amphioxus nervous system and comparative molecular genetic studies of amphioxus and tunicates have provided recent insights into the phylogenetic origin of the vertebrate nervous system. The results suggest that several of the genetic mechanisms for establishing and patterning the vertebrate nervous system already operated in the ancestral chordate and that the nerve cord of the proximate invertebrate ancestor of the vertebrates included a diencephalon, midbrain, hindbrain, and spinal cord. In contrast, the telencephalon, a midbrain-hindbrain boundary region with organizer properties, and the definitive neural crest appear to be vertebrate innovations.

Animals↗