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PubMed2001

Patterning the mammalian cerebral cortex.

When and how is the area map of the cerebral cortex set up during development? Recent studies indicate that regional pattern emerges early in cortical neurogenesis, and that this pattern does not require cues from extrinsic innervation. Studies of mutant mice indicate a role for embryonic signaling centers and for specific transcription factors in regionalizing the cortex. Thus, it is increasingly probable that the cortex is partitioned using the same types of mechanisms--and in some cases, the same gene families--that are used in patterning other parts of the embryo. This emerging model is likely to be the basis for many future studies. However, new evidence also confirms the special nature of the cerebral cortex, in that cues from developing connections appear to modify and refine the final area map.

Animals↗
PubMed2002

Olfactory maps and odor images.

The understanding of neuronal processing of olfactory stimuli has been furthered by genetic studies and specialized imaging of particular neuronal populations. Selective optical imaging of odor-induced presynaptic and postsynaptic glomerular activity in the olfactory bulb/antennal lobe has visualized odorant-responsive receptor repertoires and shown a more confined odor image at the level of projection neurons compared to their olfactory receptor neuron input. Genetic tracing of projection neurons connected to particular glomeruli has revealed a somewhat dispersed spatial map of termination areas for these neurons both in insects and in vertebrates. Modifications of the glomerular odor map have resulted in altered percepts of the corresponding odors.

Animals↗
PubMed2004

Multiple roles of ephrins during the formation of thalamocortical projections: maps and more.

The functional architecture of the cerebral cortex is based on intrinsic connections that precisely link neurons from distinct cortical laminae as well as layer-specific afferent and efferent projections. Experimental strategies using in vitro assays originally developed by Friedrich Bonhoeffer have suggested that positional cues confined to individual layers regulate the assembly of local cortical circuits and the formation of thalamocortical projections. One of these wiring molecules is ephrinA5, a ligand for Eph receptor tyrosine kinases. EphrinA5 and Eph receptors exhibit highly dynamic expression patterns in distinct regions of the cortex and thalamus during early and late stages of thalamocortical and cortical circuit formation. In vitro assays suggest that ephrinA5 is a multifunctional wiring molecule for different populations of cortical and thalamic axons. Additionally, the expression patterns of ephrinA5 during cortical development are consistent with this molecule regulating, in alternative ways, specific components of thalamic and cortical connectivity. To test this directly, the organization of thalamocortical projections was examined in mice lacking ephrinA5 gene expression. The anatomical studies in ephrinA5 knockout animals revealed a miswiring of limbic thalamic projections and changes in neocortical circuits that were predicted from the expression pattern and the in vitro analysis of ephrinA5 function.

Animals↗
PubMed1992

The functional anatomy of middle-latency auditory evoked potentials: thalamocortical connections.

1. An 8 x 8-channel microelectrode array was used to map epicortical field potentials from a 4.375 x 4.375-mm2 area in the right parietotemporal neocortex of four rats. Potentials were evoked with bilaterally presented click stimuli and with electrical stimulation of the ventral and dorsal divisions of the medial geniculate body. 2. Epicortical responses to click stimuli replicated earlier findings. The responses consisted of a positive-negative biphasic waveform (P1a and N1) in the region of primary auditory cortex (area 41) and a positive monophasic waveform (P1b) in the region of secondary auditory cortex (area 36). Two potential patterns, one at the latency of the N1 and the other at the latency of the P1b, were used to represent activation of cells within areas 41 and 36. A linear combination of these patterns was sufficient to explain from 90 to 94% of the variance of the evoked potential complex at all latencies. 3. In the same animals, epicortical responses to electrical stimulation of the ventral and dorsal divisions of the medial geniculate body were also localized to areas 41 and 36, respectively. A linear combination of potential patterns from these separate stimulation conditions was sufficient to explain from 80 to 93% of the variance of the original click-evoked potential complex at all latencies. 4. These data provide functional evidence for anatomically defined topographical thalamocortical projections to primary and secondary auditory cortex. They suggest that short-latency cortical evoked potentials (10-60 ms poststimulus) are dominated by parallel thalamocortical activation of areas 41 and 36.

Acoustic Stimulation↗
PubMed1983

The positional coding system in the early eye rudiment of Xenopus laevis, and its modification after grafting operations.

In a series of Xenopus embryos, 60-90 degrees sectors at various positions distributed around the eye rudiment were replaced with sectors grafted from the opposite position in the rudiment on the same side of the head of a donor. The majority of the operations were carried out before stage 28 (Nieuwkoop & Faber, 1956), and many before stage 26. The patterns of retinotectal connectivity which then developed were assayed electrophysiologically soon after metamorphosis. The visuotectal maps were frequently compound, giving evidence that many parts of the rudiment had already been equipped with distinct tissue positional codes by the time operations were performed (i.e. before neurogenesis). Although graft-derived sectors of retina connected to tectal sectors that were more nearly appropriate for their original positions in the rudiment than for their translocated ones, the 'handedness' of these ectopic components of the compound maps tended to bear a mirror-image relation to the major map, rather than the point-symmetrical one to be expected from a complete autonomy of mapping functions in grafted tissue. The results are discussed in relation to possible modes of organization of the developing eye, considered as a pattern-forming system.

Animals↗
PubMed1989

Projection from the superficial layers of the tectum to the pretectal complex in the cat.

The projection from the superficial layers of the tectum to the pretectal complex in the cat was examined using the retrograde transport of wheat germ agglutinin-horseradish peroxidase. Restricted injections were made into different parts of the pretectum. Neurons in the superior colliculus were found to be arranged in a mediolateral array that corresponds to the rostromedial to caudolateral array of their axon projections to the nucleus of the optic tract and posterior pretectal nucleus. These results suggest that similar parts of the retinotopic maps present in the pretectum and superior colliculus are connected. The labeled cells in the superior colliculus were located within the deep part of stratum griseum superficiale and the superficial part of stratum opticum, and were composed of multipolar cells, vertical fusiform cells and horizontal cells. We conclude from this study that the cells of origin in the superior colliculus originate in the same region to which the contralateral retinal Y-cells project and that have also the morphological diversity, as do other tecto-thalamic neurons.

Animals↗
PubMed1996

Proposed three-dimensional model for the attachment protein G of respiratory syncytial virus.

Protein G of respiratory syncytial virus (RSV) is an envelope glycoprotein that is structurally very different from its counterparts (haemagglutinin-neuraminidase and haemagglutinin) in other paramyxoviruses. In this study, we put forward a model for this unique viral envelope protein. We propose that protein G of RSV contains several independently folding regions, with the ectodomain consisting of a conserved central hydrophobic region located between two polymeric mucin-like regions. The central conserved region is probably the only relatively fixed and folded part of the ectodomain of RSV-G. This central conserved region contains four conserved cysteine residues which can form two disulphide bridges. Analysis of the proteolytic digestion products of a peptide corresponding to the central conserved region showed that one of the three theoretically possible combinations of disulphide connections could be eliminated. The final disulphide bridge assignment was established by affinity measurements with peptide variants in which different disulphide connections were formed. Additionally, peptide binding studies were used to map the binding site, at the amino acid level, of a monoclonal antibody directed against the central conserved region. These studies indicated the level of surface exposure of the amino acid side-chains. The surface exposure agreed with the structural model. The proteolytic digestion, the peptide binding studies and the affinity measurements with structural peptide variants support a structural model with disulphide connections that correspond to a structural motif called a cystine noose. This model provides a structural explanation for the location and molecular details of important antigenic sites.

Amino Acid Sequence↗
PubMed1997

Hand/face border as a limiting boundary in the body representation in monkey somatosensory cortex.

Horizontal intracortical connections may form one substrate for representational plasticity in somatosensory cortex. Electrophysiological mapping demonstrated the finer details of the representations of the hand, lower jaw, neck, and face in area 3b of normal macaque monkeys. Injections of two fluorescent tracers then defined the extent to which horizontal connections crossed from the face into the hand representations and vice versa in area 3b. Connections are widely distributed within cortical representations of skin areas innervated by cervical nerves or by the trigeminal nerve but do not cross a border defined by the anterior limit of the representation of skin innervated by the second cervical nerve. This border separates the representation of the muzzle, innervated only by the mandibular nerve, and the representation of the lower jaw and neck region, innervated by the second and third cervical nerves but overlapped by the mandibular nerve. Thus, the muzzle representation lacks connections with the hand and with the lower jaw and neck representations, but the representations of the hand and of the lower jaw and neck are strongly interconnected. Overlap of the hand and of the lower jaw and neck representations and of their horizontal intracortical connections may form one basis for expansions of the lower jaw representation into that of the hand when peripheral input from the hand is lost. Lack of connections with the rest of the face representation may limit this spread.

Afferent Pathways↗
PubMed2002

Topology of the conceptual network of language.

We define two words in a language to be connected if they express similar concepts. The network of connections among the many thousands of words that make up a language is important not only for the study of the structure and evolution of languages, but also for cognitive science. We study this issue quantitatively, by mapping out the conceptual network of the English language, with the connections being defined by the entries in a Thesaurus dictionary. We find that this network presents a small-world structure, with an amazingly small average shortest path, and appears to exhibit an asymptotic scale-free feature with algebraic connectivity distribution.

Journal Article↗
PubMedDate not supplied

[Brain biopotential mapping in emotional and cognitive pathology].

The EEG rhythms spectral power and intracortical connections were studied in depressive and schizophrenic patients in four schematically outlined main cortical quadrants. In depressive patients two cortical quadrants--right anterior and left posterior ones appeared to be predominantly involved in negative emotions regulation. Alpha-rhythm spectral power and cortical connections in these areas were decreased, pointing to their relative hyperactivation and functional disturbances. Schizophrenics patients were divided into two groups--with the predominance of "positive" and "negative" symptoms. In the first group there was revealed the decrease of the most EEG rhythms spectral power only in parietal areas, on the second one--in all cortical areas. There was also the significant alpha-rhythm spectral power asymmetry, different in the two groups of schizophrenic patients. In "positive" schizophrenics the decrease of alpha-rhythm spectral power was revealed in parietal and occipital areas of the right hemisphere, and in "negative" ones--vice versa, these results pointing of the relatively higher activation of the right posterior quadrant in the former group and of the left posterior quadrant in the latter one. In the anterior cortical quadrants the intracortical connections were however higher in the left hemisphere in "positive" and in the right one--in "negative" schizophrenics. Thus, there are some contradictory results obtained by different methods in anterior and posterior cortical quadrants in each hemisphere, these results being of opposite directions in patients with "positive" and "negative" manifestations. "Region of interest" (ROI) in schizophrenics appeared to be predominantly the frontal and temporal ones, while the "Rhythm of interest"--beta2.

Adjustment Disorders↗
PubMed1993

A model of selective synapse formation in sympathetic ganglia.

In the sympathetic system, neurons from several spinal segments are mapped onto targets in the periphery in a topographically ordered way by means of selective synaptic connections in the superior cervical ganglion. Experimental evidence points to a crucial role for chemoaffinity in establishing this topographic map. Furthermore, rearrangements of synapses after surgical manipulations indicate that this chemoaffinity is not based on rigid "key-and-lock" markers. Our model is used to study how such nonrigid markers may interact with other regulatory factors, including growth-regulating signals and the growth potential of individual neurons. In the model, these latter factors are limiting, so that an increasing number of synaptic contacts decreases the likelihood of further synapse formation. These factors are combined with chemoaffinity using a linear threshold model. The model is robust to parameter changes and reproduces experimental observations with reasonable detail. Simulation results are used to discuss characteristic experimental results, such as the substantial plasticity of the connections seen after partial denervation. A surprisingly small effect of transient hyperinnervation in the model may help explain why final connectivities are similar in two real situations with high and low degrees of transient hyperinnervation (development and adult reinnervation). It is shown that spatial restrictions on post-synaptic neurons (dendrites) may contribute significantly to the segmentally broad innervation of each ganglion cell. Finally, we discuss potential effects of presynaptic neuronal death in systems with a high degree of plasticity.

Animals↗
PubMed1999

Contribution of mitogen-activated protein kinase to stimulation of phospholipase D by the chemotactic peptide fMet-Leu-Phe in human neutrophils.

Phospholipase D (PLD) plays an important role in signaling through phosphatidylcholine (PC) and in the production of superoxide (respiratory burst) by polymorphonuclear leukocytes (PMN) stimulated by the chemoattractant fMet-Leu-Phe (fMLP). However, the regulation of PLD activity by protein kinases is not fully understood. In the present study, we have used a mitogen-activated protein (MAP) kinase inhibitor (PD 98059) to investigate a possible connection between extracellular signal-regulated kinase (ERK) and PLD activity and respiratory burst. Using a range of concentrations (3-20 microM) which inhibit ERK activity, PD 98059 inhibited PLD activity induced by fMLP in cytochalasin B-primed PMN, as assessed by production-tritiated phosphatidylethanol (PEt), phosphatidic acid (PA), and hydrolysis of PC. However, the inhibition was partial (approximately 50%), while inhibition of PC hydrolysis was almost complete, suggesting a concomitant inhibition of PLA2 activity. In addition, PD 98059 reduced fMLP-induced respiratory burst by 50%, an effect which was correlated with PLD inhibition of PLD (r = 0.981, P < 0.01), and neither did PD 98059 inhibit the PLD activity and respiratory burst induced by PKC upon its direct activation by phorbol myristate acetate. These data provide the first evidence for implication of the ERK cascade in the stimulation of PLD through Gi signaling. They further indicate that PLD stimulation by fMLP receptors occurs through two pathways, dependent and independent on MAP kinase, the former pathway being linked to superoxide production.

Enzyme Activation↗