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Auditory speech processing in the left temporal lobe: an electrical interference study.

Auditory syllable discrimination, identification, and comprehension were investigated by direct cortical electrical interference in three patients with indwelling subdural electrode arrays. Without electrical interference, patients performed similarly to matched normal subjects. With electrical interference, selective deficits were observed in the posterior superior temporal (PST) lobes of all three patients. At specific PST sites, only comprehension was impaired, while at proximal sites comprehension and identification were impaired, but discrimination remained intact. At a single PST site, all three auditory speech functions were impaired. These findings suggest that lower-level auditory speech functions can operate independent of higher-level processes, as claimed by traditional hierarchical models. However, analysis of discrimination errors revealed lexical-semantic and phonological effects, suggesting that higher-level functions also influence lower-level processing. These data can be explained by a bidirectional processing model, with differentially weighted connections.

Adolescent↗

Voltage-gated potassium channel genes are clustered in paralogous regions of the mouse genome.

Cloning of the Drosophila Shaker gene established that a neurological phenotype including locomotor dysfunction can be caused by a mutation in a voltage-gated potassium (K) channel gene. Shaker sequences have been used to isolate a large family of related K channel genes from both flies and mammals. Toward elucidating the evolutionary relationship between loci and the potential causal connection that K channels may have to mammalian genetic disorders, we report here the genetic mapping of 12-16 different murine, voltage-gated K channel genes. We find that multiple genes, in some cases from distantly related K channel subfamilies, occur in clusters in the mouse genome. These mapping results suggest that the K channel gene subfamilies arose through ancient localized gene duplication events, followed by chromosomal duplications and rearrangements as well as further gene duplication. We also note that several neurologic disorders of both mouse and human are associated with the chromosomal regions containing K channel genes.

Animals↗

Effects of selective perirhinal and postrhinal lesions on acquisition and retention of a visual discrimination task in rats.

The hippocampal region along with rhinal structures seems to support learning and memory in an important manner. Structures adjacent to the rhinal fissure in the rat have recently been suggested to be divided into the perirhinal and postrhinal cortices. Some effects of perirhinal lesions on cognitive processing are known, whereas effects of postrhinal lesions appear to be unknown. The purpose of the present study was to examine the relative effects of perirhinal and postrhinal lesions in a three-choice visual discrimination test. The results show that both types of lesions impaired acquisition of the task, but only perirhinal lesions impeded subsequent retention. Because the initial phase of acquisition was unaffected by both lesions, it is suggested that the deficits observed may be of mnemonic nature. The apparent differential involvement of the perirhinal cortex and postrhinal cortex in cognition may be associated with differences in anatomical connectivity among these structures.

Animals↗

Central connections of the pineal organ in the three-spined stickleback, Gasterosteus aculeatus L. (teleostei).

Central connections of the pineal organ of the three-spined stickleback, Gasterosteus aculeatus L., were studied by the use of horseradish peroxidase (HRP) for anterograde tracing. The pineal tract terminates bilaterally in the habenular nuclei, area praetectalis, dorsal and ventral thalamic nuclei, periventricular hypothalamus, and dorsal tegmentum. Furthermore, fibers were traced into the rostral hypothalamus, tuberal nuclei and deep tegmentum. No pinealopetal connections were observed.

Animals↗

Projections from inspiratory neurons of the nucleus retroambigualis to phrenic motoneurons in the cat.

The connection between the inspiratory neurons of the nucleus retroambigualis and the phrenic motoneurons was examined using the techniques of antidromic mapping to discover collaterals and spike-triggered averaging to detect postsynaptic potentials. Axon collaterals within the region of the C5 phrenic nucleus were found for 17 of 26 (65%) inspiratory neurons and 6 of these 17 (35%) were shown to generate excitatory postsynaptic potentials in at least one phrenic motoneuron. It was concluded that these results demonstrate a strong connection for those inspiratory neurons of the nucleus retroambigualis with a collateral within the phrenic nucleus.

Animals↗

The maturational status of thalamocortical and callosal connections of visual areas V1 and V2 in the newborn monkey.

Cytochrome oxidase (CytOx) is known to preferentially stain those regions of the visual cortex which receive direct projections from the thalamus. The pattern of CytOx stain has been used to investigate the maturation of thalamic input to areas V1 and V2 in the newborn monkey. In both areas, the intensity of CytOx activity was similar in newborns and adults. The distribution of CytOx in area V2 was not found to vary with age. In area V1, the only difference in CytOx activity in newborns was a relative immaturity of staining in layer 4C. The callosal connections of visual areas V1 and V2 were investigated by the axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase and free horseradish peroxidase. In the adult, V1 was found to be reciprocally callosally connected for a distance of 1-2.5 mm from the V1/V2 border, whilst V2 was connected for a distance of 3-8 mm from the border. In both areas, callosal connections showed a certain degree of clustering, particularly in V2 which contained 97-98% of the total number of callosal connections of these two areas. In the newborn, the number, tangential extent and clustered distribution of callosal connections were as in the adult. In the newborn, as in the adult, callosal connections coincided with regions of high CytOx activity in area V2. The results showing a relative maturity of the tangential distribution of callosal projecting neurons on the one hand, and an immaturity of thalamic projections on the other, are discussed in terms of: (1) the maturational status of the newborn monkey compared to other mammals at the moment of birth and (2) the possible role of visual experience in shaping cortical connections.

Aging↗

Reappraisal of electrical cure of atrioventricular nodal reentrant tachycardia--lessons from a modified catheter ablation technique.

A modified catheter ablation technique was studied prospectively in 29 patients with atrioventricular (AV) nodal reentrant tachycardia. A His bundle electrode catheter was used for mapping and ablation. Cathodic electroshocks (100-250 J) were delivered from the distal two electrodes (connected in common) of the His bundle catheter to the site selected for ablation. The optimal ablation site recorded the earliest retrograde atrial depolarization, simultaneous or earlier than the QRS complex, with absence of a His bundle deflection during AV nodal reentrant tachycardia. One additional electrical shock was delivered if complete abolition of retrograde VA conduction persisted for more than 30 min and AV nodal reentrant tachycardia was not inducible during isoproterenol and/or atropine administration. With a cumulative energy of 323 +/- 27 J and a mean of 2.3 +/- 0.5 shocks interruption or impairment of retrograde nodal conduction was achieved. Antegrade conduction, although modified, was preserved in 27 patients, with persistence of complete AV block in 2 patients. Two of the 27 patients still need antiarrhythmic agents to control tachycardia, the other 25 patients were free of tachycardia within a mean follow-up period of 13 +/- 2 months (range 7 to 20 months). Twenty-three patients received late follow-up electrophysiological studies (3-6 months after the ablation procedures), and the AV nodal function curves were classified into 4 types. The majority of the patients (15/23) had loss of retrograde conduction. Among the 8 patients with prolongation of retrograde conduction, 4 patients still had antegrade dual AV nodal property but all without inducible tachycardia. In conclusion, preferential interruption or impairment of retrograde conduction was the major, but not the sole, mechanism of electrical cure of AV nodal reentrant tachycardia.

Adult↗

Multiple sets of visual cortical neurons projecting transitorily through the corpus callosum.

In areas 17 and 18 of adult cats only a few neurons send bifurcating axons to more than one contralateral area or to areas in both hemispheres; most neurons seem to project to only one area. We now found that such a selective connectivity is already present at birth, i.e. several weeks before transitory callosal axons are eliminated. This is true even for those portions of cortex which will lose access to the corpus callosum: in particular different neurons project transitorily from medial area 17 to different contralateral areas. Thus cortical neurons may be induced to project to specific targets by a mechanism operating long before (and possibly independent of) the axon elimination. The latter may, however, be responsible for the final topographic organization of the connections.

Animals↗

Electrophysiology of limbic forebrain and paraventricular nucleus connections.

The connections of forebrain structures with the hypothalamic paraventricular nucleus (PVN) were examined electrophysiologically in anaesthetized male rats. Single unit recordings from 336 neurons were made within the cingulate cortex (CC, n = 78), lateral septum (LS, 114), bed nucleus of the stria terminalis (BST, 27). bed nucleus proprioris commissurae (BCA, 27) and preoptic area (POA, 90). Following PVN stimulation, some cells in all regions were identified as projecting to the PVN. Antidromic (24%), orthodromic excitatory (44%) and inhibitory (22%) responses recorded from CC units demonstrated the presence of reciprocal pathways between PVN and CC. Thirty-eight percent of LS units were antidromically identified as projecting to the PVN and these appeared to show some discrete topographic organization. Fifty-seven percent of LS units responded orthodromically to stimulation of the PVN, the majority of such responses being excitatory. Within the bed nuclei, 24% of units were antidromically identified as projecting to PVN and 70% of cells in these regions responded orthodromically following PVN stimulation, excitatory responses predominating within the BST and inhibitory responses within the BCA. Within the POA, 38% of units were identified as projecting to the PVN and the remaining units were approximately divided between orthodromic excitatory and inhibitory responses. A small proportion of antidromically identified units (less than 20%) in all regions also exhibited responses suggesting the presence of reciprocal connections with the PVN.

Animals↗

Electrophysiologic and histologic effects of dissection of the connections between the atrium and posterior part of the atrioventricular node.

OBJECTIVES: This study was designed to examine the effects of destroying the posterior approaches to the atrioventricular (AV) node. BACKGROUND: Surgical and catheter ablation procedures have been developed for the cure of AV junctional reentrant tachycardia. Some of these destroy the posterior approaches to the AV node. METHODS: Atrioventricular node function and electrical excitation of Koch's triangle and the proximal coronary sinus were examined in 18 dogs. Dissection of the posterior atrionodal connections was performed in 10 dogs and a sham procedure in 8. After 28 to 35 days, repeat electrophysiologic and mapping studies were performed to assess changes in AV node function and the routes of AV and ventriculoatrial (VA) conduction. The AV junction was then examined with light microscopy. RESULTS: The compact AV node was undamaged in eight cases (80%). In two cases minor fibrosis occurred at the posterior limit of the compact node. The right-sided posterior atrionodal connections lying between the coronary sinus orifice and the tricuspid annulus were replaced by scar tissue in all cases, but the left-sided posterior connections and the anterior connections remained intact. Atrioventricular and VA conduction intervals and refractory periods were not altered. Atrioventricular junctional echoes were present in 10 dogs before and in 7 dogs after dissection (p = 0.06). Posterior (slow pathway) retrograde exists from the AV node were present in seven dogs before and in seven dogs after dissection. However, retrograde atrial excitation was altered in four of these seven dogs, so that the site of exit from the AV node was more leftward than it had been preoperatively. The node remained responsive to autonomic blocking drugs postoperatively. Double atrial electrograms similar to slow pathway potentials were found in all dogs. CONCLUSIONS: This procedure ablates the posterior atrionodal connections but rarely damages the compact AV node. Atrioventricular node function is not impaired and the node is not denervated. The mechanism of cure of AV junctional reentrant tachycardia is probably damage to the perinodal atrium. This suggests that part of the slow AV node pathway may lie outside the compact AV node. Dual AV node exits and double atrial electrograms are present in the normal canine heart.

Animals↗

Integration of chemosensory pathways in the Drosophila second-order olfactory centers.

BACKGROUND: Behavioral responses to odorants require neurons of the higher olfactory centers to integrate signals detected by different chemosensory neurons. Recent studies revealed stereotypic arborizations of second-order olfactory neurons from the primary olfactory center to the secondary centers, but how third-order neurons read this odor map remained unknown. RESULTS: Using the Drosophila brain as a model system, we analyzed the connectivity patterns between second-order and third-order olfactory neurons. We first isolated three common projection zones in the two secondary centers, the mushroom body (MB) and the lateral horn (LH). Each zone receives converged information via second-order neurons from particular subgroups of antennal-lobe glomeruli. In the MB, third-order neurons extend their dendrites across various combinations of these zones, and axons of this heterogeneous population of neurons converge in the output region of the MB. In contrast, arborizations of the third-order neurons in the LH are constrained within a zone. Moreover, different zones of the LH are linked with different brain areas and form preferential associations between distinct subsets of antennal-lobe glomeruli and higher brain regions. CONCLUSIONS: MB is known to be an indispensable site for olfactory learning and memory, whereas LH function is reported to be sufficient for mediating direct nonassociative responses to odors. The structural organization of second-order and third-order neurons suggests that MB is capable of integrating a wide range of odorant information across glomeruli, whereas relatively little integration between different subsets of the olfactory signal repertoire is likely to occur in the LH.

Animals↗

Structure of the rotor of the bacterial flagellar motor revealed by electron cryomicroscopy and single-particle image analysis.

The FliF ring is the base for self-assembly of the bacterial flagellum and the FliF/FliG ring complex is the core of the rotor of the flagellar motor. We report the structures of these two ring complexes obtained by electron cryomicroscopy and single-particle image analysis at 22A and 25A resolution, respectively. Direct comparison of these structures with the flagellar basal body made by superimposing the density maps on the central section reveals many interesting features, such as how the mechanically stable connection between the ring and the rod is formed, how directly FliF domains are involved in the near axial density of the basal body forming the proximal end of the central channel for a potential gating mechanism, some indication of flexibility in the connection of FliF and FliG, and structural and functional similarities to the head-to-tail connectors of bacteriophages.

Bacteria↗

Voltage-sensitive dye imaging of intervibrissal fur-evoked activity in the rat somatosensory cortex.

The intervibrissal fur-evoked activity in the rat somatosensory cortex was investigated using high-resolution optical imaging with a voltage-sensitive dye. The optical imaging revealed that the intervibrissal fur representation forms a U-shaped band around the borders of the posteromedial barrel subfield (PMBSF), and that this representation is characterized by a rostral-to-caudal somatotopic organization. When GABA(A)-mediated inhibition was partially suppressed by treatment with bicuculline, stimulation of the intervibrissal fur elicited spreading of an excitation wave in an area outside the PMBSF. The spreading wave propagated in both directions along the aforementioned U-shaped band of cortex, but barely invaded the center of the PMBSF. These imaging results suggest a distinct subdivision of cortex adjacent to, but outside, the PMBSF in the rat somatosensory cortex; this region receives input from intervibrissal fur, and seems to process its sensory information through well-developed local horizontal connections.

Animals↗

Left-sided atrial flutter: characterization of a novel complication of pediatric lung transplantation in an acute canine model.

BACKGROUND: Postoperative atrial flutter has been observed in approximately 10% of children undergoing lung transplantation at our institution. We hypothesized that the left atrial anastomoses made to establish pulmonary venous continuity provide the primary electrophysiologic substrates for atrial flutter. OBJECTIVES: Our objectives were (1) to determine whether the left atrial suture lines alone are sufficient to produce atrial flutter in an acute canine model of lung transplantation and (2) to characterize any resulting reentrant circuits to surgically ablate the atrial flutter. METHODS: Supported by cardiopulmonary bypass, adult dogs (n = 10) underwent bilateral pneumonectomies. The left atrial anastomotic suture lines were simulated by dividing the tissue between the ostia of the transected superior and inferior pulmonary veins and closing the resulting defects. Bilateral suture lines were placed in group 1 (n = 6) to simulate bilateral lung transplantation. In group 2 (n = 4), only a left-sided suture line was placed to represent single lung transplantation. Unipolar 253-point biatrial endocardial mapping electrodes were inserted via bilateral ventriculotomies. Atrial flutter was induced by atrial burst pacing, and activation sequence maps were generated. In five of six cases in group 1, a T-incision connecting the two suture lines and the mitral anulus was then made. In group 2, a single incision from the suture line to the mitral anulus was performed in each case. Burst pacing was subsequently repeated. RESULTS: Atrial flutter could not be induced after bypass alone in any case. After simulated lung transplantation, sustained atrial flutter was reproducibly induced in 10 of 10 dogs. The mean cycle length in all dogs was 133 +/- 7 msec. There was no significant difference in mean cycle length or activation sequence patterns between groups 1 and 2. The reentrant circuit was confined to the left atrium. Each simulated left atrial anastomosis created a zone of conduction block around which circus movement could occur. In group 1, either suture line functioned as the central obstacle. Atrial flutter was terminated in five of five dogs in group 1 by means of the T-incision and in all four dogs in group 2 with the incision connecting the suture line to the mitral anulus. CONCLUSIONS: (1) In an acute canine model of lung transplantation, each left atrial suture line alone provides an electrophysiologic substrate for atrial flutter by creating a zone of conduction block around which circus movement can occur. (2) Extending this zone of block to the mitral anulus, together with interruption of the isthmus of tissue between the two suture lines present after bilateral lung transplantation, terminates the atrial flutter in this model and may have an application prophylactically at the time of lung transplantation in children to prevent postoperative atrial flutter.

Anastomosis, Surgical↗

Monitoring the effects of drug treatment in rat models of disease by serum protein analysis.

In this review we list from literature investigations on rat serum proteins using electrophoretic techniques in connection with drug testing. From our own research work, we provide annotated two-dimensional maps of rat serum proteins under control and experimental conditions. Emphasis is on species-specific components and on the effects of acute and chronic inflammation. We discuss our project of structural proteomics on rat serum as a minimally invasive approach to pharmacological investigation, and we outline a typical experimental plan for drug testing according to the above guidelines. We then report in detail on the results of our trials of anti-inflammatory drugs on adjuvant arthritis, an animal model of disease resembling in many aspects human rheumatoid arthritis. We demonstrate a correlation between biochemical parameters and therapeutic findings and outline the advantages of the chosen methodological approach, which proved also sensitive in revealing "side effects" of the test drugs. In an appendix we describe our experimental protocol when performing two-dimensional electrophoresis of rat serum.

Animals↗

Dynamical features simulated by recurrent neural networks.

The evolution of two-dimensional neural network models with rank one connecting matrices and saturated linear transfer functions is dynamically equivalent to that of piecewise linear maps on an interval. It is shown that their iterative behavior ranges from being highly predictable, where almost every orbit accumulates to an attracting fixed point, to the existence of chaotic regions with cycles of arbitrarily large period.

Journal Article↗

Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering.

BACKGROUND: Calmodulin is a calcium-activated regulatory protein which can bind to many different targets. The protein resembles a highly flexible dumbbell, and bends in the middle as it binds. This and other motions must be understood to formulate a realistic model of calmodulin function. RESULTS: Using the Bragg reflections from X-ray crystallography, a multiple-conformer refinement of a calmodulin-peptide complex shows anisotropic displacements, with high variations of dihedral angles in several nonhelical domains: the flexible linker; three of the four calcium-binding sites (including both of the N-terminal sites); and a turn connecting the C-terminal EF-hand calcium-binding domains. Three-dimensional maps of the large scale diffuse X-ray scattering data show isotropic liquid-like motions with an unusually small correlation length. Three-dimensional maps of the small scale diffuse streaks show highly coupled, anisotropic motions along the head-to-tail molecular packing direction in the unit cell. There is also weak coupling perpendicular to the head-to-tail packing direction, particularly across a cavity occupied by the disordered linker domain of the molecule. CONCLUSIONS: Together, the Bragg and diffuse scattering present a self-consistent description of the motions in the flexible linker of calmodulin. The other mobile regions of the protein are also of great interest. In particular, the high variations in the calcium-binding sites are likely to influence how strongly they bind ions. This is especially important in the N-terminal sites, which regulate the activity of the molecule.

Algorithms↗

Cell dynamics of folding in two-dimensional model proteins.

BACKGROUND: Functionally useful proteins are sequences of amino acids that fold rapidly under appropriate conditions into their native states. It is believed that rapid folders are sequences for which the folding dynamics entail the exploration of restricted conformations-the phase space can be thought of as a folding funnel. While there are many experimentally accessible predictions pertaining to the existence of such funnels and a coherent picture of the kinetics of folding has begun to emerge, there have been relatively few simple studies in the controlled setting of well-characterized lattice models. RESULTS: We design rapidly folding sequences by assigning the strongest couplings to the contacts present in a target native state in a two-dimensional model of heteropolymers. Such sequences have large folding transition temperatures and low glass transition temperatures. The dependence of median folding times on temperature is investigated. The pathways to folding and their dependence on the temperature are illustrated via a study of the cell dynamics-a mapping of the dynamics into motion within the space of the maximally compact cells. CONCLUSIONS: Folding funnels can be defined operationally in a coarse-grained sense by mapping the states of the system into maximally compact conformations and then by identifying significant connectivities between them.

Models, Chemical↗