2,503 research outputs found

    GABA-enhanced collective behavior in neuronal axons underlies persistent gamma-frequency oscillations

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    Gamma (30–80 Hz) oscillations occur in mammalian electroencephalogram in a manner that indicates cognitive relevance. In vitro models of gamma oscillations demonstrate two forms of oscillation: one occurring transiently and driven by discrete afferent input and the second occurring persistently in response to activation of excitatory metabotropic receptors. The mechanism underlying persistent gamma oscillations has been suggested to involve gap-junctional communication between axons of principal neurons, but the precise relationship between this neuronal activity and the gamma oscillation has remained elusive. Here we demonstrate that gamma oscillations coexist with high-frequency oscillations (>90 Hz). High-frequency oscillations can be generated in the axonal plexus even when it is physically isolated from pyramidal cell bodies. They were enhanced in networks by nonsomatic -aminobutyric acid type A (GABAA) receptor activation, were modulated by perisomatic GABAA receptor-mediated synaptic input to principal cells, and provided the phasic input to interneurons required to generate persistent gamma-frequency oscillations. The data suggest that high-frequency oscillations occurred as a consequence of random activity within the axonal plexus. Interneurons provide a mechanism by which this random activity is both amplified and organized into a coherent network rhythm

    Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

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    Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in γ-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance

    Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by Maxicircle MLST and next generation sequencing

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    Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles (∼20 kb) and thousands of minicircles (0.5–10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30–35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs. Methodology/Principal Findings To describe intra-DTU diversity, we developed a highly resolutive maxicircle multilocus sequence typing (mtMLST) scheme based on ten gene fragments. A panel of 32 TcI isolates was genotyped using the mtMLST scheme, GPI, mini-exon and 25 microsatellite loci. Comparison of nuclear and mitochondrial data revealed clearly incongruent phylogenetic histories among different geographical populations as well as major DTUs. In parallel, we exploited read depth data, generated by Illumina sequencing of the maxicircle genome from the TcI reference strain Sylvio X10/1, to provide the first evidence of mitochondrial heteroplasmy (heterogeneous mitochondrial genomes in an individual cell) in T. cruzi. Conclusions/Significance mtMLST provides a powerful approach to genotyping at the sub-DTU level. This strategy will facilitate attempts to resolve phenotypic variation in T. cruzi and to address epidemiologically important hypotheses in conjunction with intensive spatio-temporal sampling. The observations of both general and specific incidences of nuclear-mitochondrial phylogenetic incongruence indicate that genetic recombination is geographically widespread and continues to influence the natural population structure of TcI, a conclusion which challenges the traditional paradigm of clonality in T. cruzi

    Imaging the spotty surface of Betelgeuse in the H band

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    This paper reports on H-band interferometric observations of Betelgeuse made at the three-telescope interferometer IOTA. We image Betelgeuse and its asymmetries to understand the spatial variation of the photosphere, including its diameter, limb darkening, effective temperature, surrounding brightness, and bright (or dark) star spots. We used different theoretical simulations of the photosphere and dusty environment to model the visibility data. We made images with parametric modeling and two image reconstruction algorithms: MIRA and WISARD. We measure an average limb-darkened diameter of 44.28 +/- 0.15 mas with linear and quadratic models and a Rosseland diameter of 45.03 +/- 0.12 mas with a MARCS model. These measurements lead us to derive an updated effective temperature of 3600 +/- 66 K. We detect a fully-resolved environment to which the silicate dust shell is likely to contribute. By using two imaging reconstruction algorithms, we unveiled two bright spots on the surface of Betelgeuse. One spot has a diameter of about 11 mas and accounts for about 8.5% of the total flux. The second one is unresolved (diameter < 9 mas) with 4.5% of the total flux. Resolved images of Betelgeuse in the H band are asymmetric at the level of a few percent. The MOLsphere is not detected in this wavelength range. The amount of measured limb-darkening is in good agreement with model predictions. The two spots imaged at the surface of the star are potential signatures of convective cells.Comment: 10 pages, 10 figures, accepted for publication in A&A, references adde

    Expressive aphasia in a patient with recent dual-chamber cardioverter-defibrillator implantation: A preventable complication

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    Transvenous pacemaker and/or defibrillator lead placement into the left heart chambers is rarely done. Approximately a third of such cases reported in the literature presented with signs of thromboembolism, mostly neurological deficits. We describe a patient who presented with a cerebrovascular accident three months after inadvertent and unrecognized lead placement into the left atrium and ventricle through a sinus venosus atrial septal defect. Implant techniques to avoid this complication are discussed. (Cardiol J 2011; 18, 2: 197-199

    Test results of Spacelab 2 infrared telescope focal plane

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    The small helium cooled infrared telescope for Spacelab 2 is designed for sensitive mapping of extended, low-surface-brightness celestial sources as well as highly sensitive investigations of the shuttle contamination environment (FPA) for this mission is described as well as the design for a thermally isolated, self-heated J-FET transimpedance amplifier. This amplifier is Johnson noise limited for feedback resistances from less than 10 to the 8th power Omega to greater than 2 x 10 to the 10th power Omega at T = 4.2K. Work on the focal plane array is complete. Performance testing for qualification of the flight hardware is discussed, and results are presented. All infrared data channels are measured to be background limited by the expected level of zodiacal emission

    Seizure initiation in infantile spasms vs. focal seizures: proposed common cellular mechanisms

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    Infantile spasms (IS) and seizures with focal onset have different clinical expressions, even when electroencephalography (EEG) associated with IS has some degree of focality. Oddly, identical pathology (with, however, age-dependent expression) can lead to IS in one patient vs. focal seizures in another or even in the same, albeit older, patient. We therefore investigated whether the cellular mechanisms underlying seizure initiation are similar in the two instances: spasms vs. focal. We noted that in-common EEG features can include (i) a background of waves at alpha to delta frequencies; (ii) a period of flattening, lasting about a second or more – the electrodecrement (ED); and (iii) often an interval of very fast oscillations (VFO; ~70 Hz or faster) preceding, or at the beginning of, the ED. With IS, VFO temporally coincides with the motor spasm. What is different between the two conditions is this: with IS, the ED reverts to recurring slow waves, as occurring before the ED, whereas with focal seizures the ED instead evolves into an electrographic seizure, containing high-amplitude synchronized bursts, having superimposed VFO. We used in vitro data to help understand these patterns, as such data suggest cellular mechanisms for delta waves, for VFO, for seizure-related burst complexes containing VFO, and, more recently, for the ED. We propose a unifying mechanistic hypothesis – emphasizing the importance of brain pH – to explain the commonalities and differences of EEG signals in IS versus focal seizures
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