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Cavotricuspid isthmus conduction is dependent on underlying anatomic bundle architecture: observations using a maximum voltage-guided ablation technique.

OBJECTIVES: We hypothesized an ablation strategy directly targeting muscle bundles might demonstrate functionally distinct "routes" of conduction, potentially shortening ablation times. BACKGROUND: Pathological study demonstrated that the cavotricuspid isthmus is composed of distinct anatomically defined bundles, many with intervening gaps of connective tissue. METHODS: A line was mapped in the "6 o'clock" region and bipolar electrogram amplitude measured during pullback. Zones of peak voltage were ablated first regardless of position. RF was delivered using either a 5-mm externally irrigated catheter, or an 8-mm nonirrigated catheter. The zone of largest remaining voltage was then sequentially targeted until conduction. RESULTS: Eighteen patients were recruited and followed for 7.9 +/- 1.9 months block occurred (mean age 64 +/- 11.6 years, male:female ratio 14:4). Bi-directional block was achieved in all patients with recurrence of atrial flutter in 1 patient. Mean total RF times was 4.7 +/- 2.8 minutes with a mean of 6.1 +/- 3.3 applications, procedure time was 127.3 +/- 37.7 minutes, and fluoroscopy time was 25.5 +/- 12.0 minutes. Two patterns of block were observed in the study group. Pattern A described no change in conduction times until block, observed in 6 (33%); pattern B described a stepwise block with discrete "jumps," observed in 12 (67%). CONCLUSIONS: An ablation strategy targeting high-voltage isthmus electrograms obviates the need for a complete anatomic line. This finding together with discrete "jumps" during ablation is consistent with the concept of conduction over discrete bundles rather than a diffuse sheet of muscle.

Adult↗

Cardiac near-field morphology during conduction around a microscopic obstacle--a computer simulation study.

In a recent paper, we described the behavior of the cardiac electric near-field, E, parallel to the tissue surface during continuous conduction. We found that the tip of E describes a vector-loop during depolarization with the peak field, E, pointing opposite to the direction of propagation, phiI(m). Experimentally recorded loop morphologies of E, however, frequently showed significant deviations from the theoretically predicted behavior. We hypothesized that this variety of morphologies might be caused by conduction obstacles at a microscopic size scale. This study examines the influence of obstacles on the morphology of vector loops of E and whether the peak of distorted loops remains a reliable indicator for the direction of propagation. We used a computer model of a sheet of cardiac tissue with a central conduction obstacle immersed in an unbounded volume conductor. We studied the loop morphologies of E and the differences between the intracellularly determined direction of propagation, phiI(m), and the direction of E, phiE. Distortions of the vector loop were morphologically similar to those observed experimentally. Differences between phiI(m) and phiE were less than 18 degrees at all observation sites. The obstacle led to deformations of the loop morphology, particularly during the initial and terminal phases, and to a lesser degree near the instant of E. We concluded that E is a reliable indicator of phiI(m).

Animals↗

Rhombencephalic neural crest segmentation is preserved throughout craniofacial ontogeny.

To investigate the influence of hindbrain segmentation on craniofacial patterning we have studied the long term fate of neural crest (NC) subpopulations of individual rhombomeres (r), using quail-chick chimeras. Mapping of all skeletal and muscle connective tissues developing from these small regions revealed several novel features of the cranial neural crest. First, the mandibular arch skeleton has a composite origin in which the proximal elements are r1+r2 derived, whereas more distal ones are exclusively midbrain derived. The most proximal region of the lower jaw is derived from second arch (r4) NC. Second, both the lower jaw and tongue skeleton display an organisation which precisely reflects the rostrocaudal order of segmental crest deployment from the embryonic hindbrain. Third, cryptic intraskeletal boundaries, which do not correspond to anatomical landmarks, form sharply defined interfaces between r1+r2, r4 and r6+r7 crest. Cells that survive the early apoptotic elimination of premigratory NC in r3 and r5 are restricted to tiny contributions within the 2nd arch (r4) skeleton. Fourth, a highly constrained pattern of cranial skeletomuscular connectivity was found that precisely respects the positional origin of its constitutive crest: each rhombomeric population remains coherent throughout ontogeny, forming both the connective tissues of specific muscles and their respective attachment sites onto the neuro- and viscerocranium. Finally, focal clusters of crest cells, confined to the attachment sites of branchial muscles, intrude into the otherwise mesodermal cranial base. In the viscerocranium, an equally strict, rhombomere-specific matching of muscle connective tissues and their attachment sites is found for all branchial and tongue (hypoglossal) muscles. This coherence of segmental crest populations explains how cranial skeletomuscular pattern can be implemented and conserved despite evolutionary changes in the shapes of skeletal elements.

Animals↗

Brain and heart specific alteration of methamphetamine (MAP) distribution in MAP-sensitized rat.

The repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the high accumulation of MAP was observed in the MAP-sensitized animal brain, which suggested that this phenomenon is an important factor in the development or expression of behavioral sensitization. The purpose of the present study is to elucidate the MAP distribution in the MAP-sensitized rat using gas chromatography/mass spectrometry (GC/MS). As a result, the MAP distribution in the heart at 10 min when showing a high accumulation of MAP in the MAP-sensitized rat brain was significantly higher than that of the control rat, whereas no significant differences in the liver, kidney, abdominal muscle, femoral muscle and blood were observed. In the brain and heart, there was no different distribution at 1 min, reflecting only the influx process from blood to brain and heart. On the contrary, there was the significant difference at 10 min, reflecting both the influx and efflux process, suggesting that the efflux process of MAP from brain or heart to blood may be slow due to MAP sensitization. In conclusion, it was clear that the brain and heart specific alteration of the MAP distribution occurred in the MAP sensitization. It was considered that the high accumulation of MAP in the MAP-sensitized rat brain may be related to the expression of behavioral sensitization and that the delayed efflux of MAP in the MAP-sensitized rat heart may be connected with the cardiac toxicity.

Animals↗

[Some regularities in the development of encrusting colonies of Cribrilina annulata (Fabricius, 1780)].

The growth of encrusting colonies was studied with mathematical model. It was shown that encrusting growth takes place under increasing competition for the substrate inside the colony. The model was tested on the example of Cribrilina annulata collected in White Sea on Laminaria saccarina. All colonies were mapped, zooids were measured and genealogical connections between them were established. A number of gradients were revealed by statistical methods. The intensity of budding decreases in astogeny according to theoretical predictions. It was shown that development of Cribrilina annulata colonies is strictly determined by gradients that can be caused by shortage of substrate space. It leads to the suppression of budding and changing in zooid size. Increasing substrate shortage is predictable and caused by the regularities in of zooid budding. The growth of colony stops after exhausting of potentially available substrate.

Animals↗

Effect of aniracetam on phosphatidylinositol transfer protein alpha in cytosolic and plasma membrane fractions of astrocytes subjected to simulated ischemia in vitro.

Brain ischemia affects phosphoinositide metabolism and the level of lipid-derived second messengers. Phosphatidylinositol transfer proteins (PI-PTs) are responsible for the transport of phosphatidylinositol (PI) and other phospholipids through membranes. Isoform of PI-TPs (PI-TPalpha) is an essential component in ensuring substrate supply for phospholipase C (PLC). The current study was conducted to examine potential effect of aniracetam on PI-TPalpha expression and to characterize the PI-TPalpha isoform distribution between membrane and cytosol fractions of astrocytes exposed to simulated ischemia in vitro. After 8 h period of ischemia, the level of PI-TPalpha was significantly higher in cytosol (by about 28%) as well as in membrane fraction (by about 80%) in comparison with control. We have found that aniracetam treatment of astrocytes in normoxia significantly increased the level of PI-TPalpha in membrane fraction with a maximal effect at 0.1 microM concentration of aniracetam (by about 195% of control). In membrane fractions of ischemic cells, aniracetam increased PI-TPalpha expression in a concentration-dependent manner. In ischemic cells, aniracetam (10 microM) has elevated PI-TPalpha expression up to 155% and 428% in cytosolic and membrane fractions in comparison with ischemic untreated cells, respectively. The study has shown that aniracetam significantly activates PI-TPalpha in cell membrane fraction and this effect might be connected with previously described activation of MAP kinase cascade.

Animals↗

Intrinsic connections of macaque striate cortex: axonal projections of cells outside lamina 4C.

We have exploited a technique for making small injections of horseradish peroxidase into single cortical laminae in order to study axonal projections in macaque striate cortex. In the preceding paper (Fitzpatrick, D., J. S. Lund, and G. G. Blasdel (1985) J. Neurosci. 5: 3329-3349) we examined the projections of cells in lamina 4C--cells that receive most of their input from the lateral geniculate nucleus. The present paper deals with the projections of neurons that lie outside of lamina 4C. Among our findings are several projections that previously had not been described in the monkey. These include: a strong and precise (point-to-point) projection from lamina 4B to lamina 2/3A, a reciprocal projection from 2/3A back to 4B, a definite projection from lamina 4B to 5B, as well as a prominent input to lamina 6 from 5B. In many cases, we find it possible to trace the flow of visual information through several "circuits" in striate cortex that have, as their output, projections to extrastriate cortex or to the brainstem. Our results offer additional insights in this regard since we are able, in many cases, to compare the lateral spreads of particular projections. These vary and can be separated into at least three categories: those that terminate in a precise, point-to-point, fashion, those that spread widely, and those that terminate in a laterally periodic fashion. In several cases we find evidence for a correlation between specific patterns of projection and known physiological differences between the topographies of laminae that are connected. In cases where two laminae possess similar topographies (for example, where both contain orderly maps for orientation) their interconnections appear precise, with little diffuse spread. In cases where two laminae are characterized by strikingly different topographies (where, for example, one contains an orderly map for orientation and the other a precise map for retinotopic position, but no specificity for orientation), the connections appear more diffuse.

Animals↗

A physiological measure of shifting connections in the Rana pipiens retinotectal system.

The retinotectal connections of developing Rana tadpoles and froglets have been studied using light-pipe techniques to directly assay the pattern of the projection from the retina to the tectum. The projection site of the retina surrounding the optic nerve head was determined at two different stages of development (late larval and metamorphic frog) on the same animal. Small electrolytic marker lesions were used to mark the tectal sites to which the optic nerve head projected at these two times. Comparison of the positions of the two lesions gives a direct measure of the shift in the projection during the interlesion time interval of one week. The results indicate a shift in the projection of 275 micron week-1 in late larval life. Previous work in Xenopus using the light-pipe techniques indicated a qualitatively similar shift during equivalent stages of development, but significantly smaller in magnitude. In the present study, topographic postsynaptic units could be recorded at all stages investigated, indicating functional synapses between the optic nerve fibres and the tectum. Thus, these studies offer evidence of a significant shift in the functional connection pattern of the amphibian retinotectal map during development, in agreement with the recent anatomical data from other laboratories on the Rana and goldfish visual system.

Animals↗

Implementation of action sequences by a neostriatal site: a lesion mapping study of grooming syntax.

The neostriatum and its connections control the sequential organization of action ("action syntax") as well as simpler aspects of movement. This study focused on sequential organization of rodent grooming. Grooming syntax provides an opportunity to study how neural systems coordinate natural patterns of serial order. The most stereotyped of these grooming patterns, a "syntactic chain," has a particularly stereotyped order that recurs thousands of times more often than could occur by chance. The purpose of the present study was to identify the crucial site within the striatopallidal system where lesions disrupt the syntax or serial order of syntactic grooming chains without disrupting constituent movements. Small excitotoxin lesions were made using quinolinic acid at bilateral sites within the dorsolateral, dorsomedial, ventrolateral, or ventromedial neostriatum, or in the ventral pallidum or globus pallidus of rats. An objective technique for mapping functional lesions was used to quantify cell death and to map precisely those lesions that disrupted grooming syntax. Our results identified a single site within the anterior dorsolateral neostriatum, slightly more than a cubic millimeter in size (1.3 x 1.0 x 1.0 mm), as crucial to grooming syntax. Damage to this site did not disrupt the ability to emit grooming actions. By contrast, damage to sites in the ventral pallidum and globus pallidus impaired grooming actions but left the sequential organization of grooming syntax intact. Neural circuits within this crucial "action syntax site" seem to implement sequential patterns of behavior as a specific function.

Animals↗

Interaction foci, information synthesis, and mental activity.

The cerebral organization of mental activity is based on neural integration, specialization of functions, and the combination of rigid and flexible connections. These principles are embodied in dynamic structures, interaction foci that are detectable in the cortex during intellectual activity by means of the intracortical interaction mapping technique. Interaction foci comprise centers of cortical connections. A focus consists of neuronal groups connected by rigid connections, based on structural changes in the synapses. Each of the groups has its own frequency characteristics and is connected by flexible connections constructed on the principle of iso-lability, with neural elements at the periphery which are isorhythmic to it. The construction of interaction focus supports the synthesis of information arriving from sense organs and centers of motivations, and extractable from memory. Information synthesis underlies mental functions, the cerebral basis for which includes a rigid nucleus and a system of peripheral connections, the configuration of which may vary, thus controlling the uniqueness of a given mental experience. The principle of specialization of functions is manifested in the fact that the topography of interaction foci varies for different mental acts. In the case of perception the projection cortex is the integration center; in the case of thinking, the associative zones of the cortex are the integrative center. Imaginal thinking is primarily associated with the parietotemporal, and abstract thinking with the frontal, divisions of the cortex. Evidently, the two principle functions of consciousness are also spatially separated: integration of the "Self", which includes the volitional principle, and communication.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Topographical maps as complex networks.

The neuronal networks in the mammalian cortex are characterized by the coexistence of hierarchy, modularity, short and long range interactions, spatial correlations, and topographical connections. Particularly interesting, the latter type of organization implies special demands on developing systems in order to achieve precise maps preserving spatial adjacencies, even at the expense of isometry. Although the object of intensive biological research, the elucidation of the main anatomic-functional purposes of the ubiquitous topographical connections in the mammalian brain remains an elusive issue. The present work reports on how recent results from complex network formalism can be used to quantify and model the effect of topographical connections between neuronal cells over the connectivity of the network. While the topographical mapping between two cortical modules is achieved by connecting nearest cells from each module, four kinds of network models are adopted for implementing intramodular connections, including random, preferential-attachment, short-range, and long-range networks. It is shown that, though spatially uniform and simple, topographical connections between modules can lead to major changes in the network properties in some specific cases, depending on intramodular connections schemes, fostering more effective intercommunication between the involved neuronal cells and modules. The possible implications of such effects on cortical operation are discussed.

Animals↗

A biologically inspired neural net for trajectory formation and obstacle avoidance.

In this paper we present a biologically inspired two-layered neural network for trajectory formation and obstacle avoidance. The two topographically ordered neural maps consist of analog neurons having continuous dynamics. The first layer, the sensory map, receives sensory information and builds up an activity pattern which contains the optimal solution (i.e. shortest path without collisions) for any given set of current position, target positions and obstacle positions. Targets and obstacles are allowed to move, in which case the activity pattern in the sensory map will change accordingly. The time evolution of the neural activity in the second layer, the motor map, results in a moving cluster of activity, which can be interpreted as a population vector. Through the feedforward connections between the two layers, input of the sensory map directs the movement of the cluster along the optimal path from the current position of the cluster to the target position. The smooth trajectory is the result of the intrinsic dynamics of the network only. No supervisor is required. The output of the motor map can be used for direct control of an autonomous system in a cluttered environment or for control of the actuators of a biological limb or robot manipulator. The system is able to reach a target even in the presence of an external perturbation. Computer simulations of a point robot and a multi-joint manipulator illustrate the theory.

Avoidance Learning↗

A candidate pathway for a visual instructional signal to the barn owl's auditory system.

Many organisms use multimodal maps to generate coherent neuronal representations that allow adequate responses to stimuli that excite several sensory modalities. During ontogeny of these maps, one modality typically acts as the dominant system the other modalities are aligned to. A well studied model for the alignment of sensory maps is the calibration of the auditory space map by the visual system in the optic tectum of the barn owl. However, a projection from the optic tectum to the site of plasticity in the auditory pathway that could deliver an instructive signal has not been found so far. We have analyzed the development of the connectivity between the bimodal (visual and auditory) map of space in the barn owl's optic tectum and the auditory space map in the inferior colliculus with tracing methods and intracellular fills. Neurons in the tectal stratum griseum centrale were found to be suited to deliver an alignment signal from the visual midbrain to the auditory pathway. These neurons are presumably part of the efferent tectal projection pathway that mediates head saccades. The implications of a sensory alignment signal possibly being delivered by a (pre)motor command pathway are discussed.

Animals↗

Polymerase chain reaction mediated localization of RFLP clones to microisolated translocation chromosomes of barley.

A new strategy has been devised and used for the physical localization of genetically mapped restriction fragment length polymorphism (RFLP) clones to barley chromosomes. Morphologically distinct translocation chromosomes from synchronized root-tip meristems were microisolated and their DNA was used as a template for polymerase chain reaction with sequence-specific primers. Four RFLP clones were assigned to cytologically defined segments of chromosome 5. This related approximately one-third of the map length of linkage group 5 to approximately one-fifth of the mitotic metaphase length of chromosome 5. The technique may substantially contribute to the connection of the RFLP-based genetic linkage maps with cytological markers of the barley chromosomes.

Base Sequence↗

Models of activity-dependent neural development.

What makes a useful model of neural development? One important contribution of modeling is to demonstrate that proposed biological mechanisms can be sufficient to account for experimental results. The Von der Malsburg model is a classic example. But such demonstrations alone do not provide tools to experimentally distinguish one mechanism from another. To draw such distinctions, the connection between measurable biological quantities and developmental outcomes must be established. Perhaps the most important task for the future of developmental modeling is to deepen the connection between theory and experiment. Experimentally, this requires detailed and difficult measurements or experimental perturbations of the correlations among inputs and the intracortical connectivity existing during development. Simultaneous measurement of the maps of spatial phase and orientation of mature simple cells will provide important information for the understanding of orientation column development. Theoretically, the number of open problems is enormous. How will inclusion of additional plasticity mechanisms, such as sprouting and retraction of synapses or plasticity of intracortical connections, alter the analytical understanding thus far achieved? What precisely determines the width of orientation columns in the model presented here? Can the relationship between ocular dominance and orientation columns be understood from developmental rules in a testable way? The existing framework may be extended to a three-dimensional cortex and to more complex models of intracortical connectivity. It may also be applied to other developmental phenomena including the development of lamination in the LGN (Shatz and Stryker, 1988; Hahm et al., 1991), the formation of visual maps in experimentally altered auditory cortex (Roe et al., 1990, 1992), and the mapping of visual and auditory maps in the optic tectum (Knudsen and Brainard, 1991; Brainard and Knudsen, 1993). For each system the goal is to develop testable predictions as to the patterns of activity and connectivity that could or could not lead to the results observed given a proposed mechanism of plasticity. Incorporation of deeper levels of biophysical realism will extend, deepen, and perhaps fundamentally alter the framework presented here. An important goal for the future will be to understand the computational and functional significance of developmental rules. Activity-dependent, competitive mechanisms of synaptic plasticity appear to play an important role in many processes of late neural development, where an initially rough connectivity pattern refines to a precise, mature pattern. A prominent example is the formation of ocular dominance columns in the visual cortex of many mammals. These processes may be modeled at several levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Cortical connectivity in schizophrenic patients with positive and negative symptoms ].

The paper is dedicated to the problem of disturbed "connectivity" between different cortical areas in schizophrenic patients with the dominance of "negative" and "positive" symptoms. The architecture of cortical connections in high-frequency range of the beta rhythm (beta 2, 20-40 Hz) was studied in three groups of right-handed men: healthy control group (16 subjects) and schizophrenic patients with the dominance of positive (16 subjects) and negative (22 subjects) symptoms assessed by the SAPS and SANS scales. Two versions of the Intracortical Interaction Mapping (IIM) technique of examination of cortical connections were used. In the 1st version, mean connection frequencies in the beta 2-rhythm for each group were analyzed. In the 2nd version, the most typical for a given group connection frequencies were studied. Additionally, since the IIM technique is rather new, coherence function in the beta 2-rhythm calculated by the standard way was also taken into account. The obtained results made it possible to reveal the derangements in the system of cortical interactions in schizophrenic patients.

Beta Rhythm↗

A model for the coordinated development of columnar systems in primate striate cortex.

The existence of patchy regions in primate striate cortex in which orientation selectivity is reduced, and which lie in the centers of ocular dominance stripes is well established (Hubel and Livingstone 1981). Analysis of functional maps obtained with voltage sensitive dyes (Blasdel and Salama 1986) has suggested that regions where the spatial rate of change of orientation preference is high, tend to be aligned either along the centers of ocular dominance stripes, or to intersect stripe borders at right angles. In this paper I present results from a developmental model which show that a tendency for orientation selectivity to develop more slowly in the centers of ocular dominance stripes would lead to the observed relationships between the layout of ocular dominance and the map of orientation gradient. This occurs despite the fact that there is no direct connection between the measures of preferred orientation (from which the gradient map is derived) and orientation selectivity (which is independent of preferred orientation). I also show that in both the monkey and the model, orientation singularities have an irregular distribution, but tend to be concentrated in the centers of the ocular dominance stripes. The average density of singularities is about 3/lambda 2 theta, where lambda theta is the period of the orientation columns. The results are based on an elaboration of previous models (Swindale 1980, 1982) which show how, given initially disordered starting conditions, lateral interactions that are short-range excitatory and long-range inhibitory can lead to the development of patterns of orientation or ocular dominance that resemble those found in monkey striate cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗