155 research outputs found

    Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

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    Neuromodulation by serotonin (5-HT) could link behavioral state and environmental events with sensory processing. Within the auditory system, the presence of 5-HT alters the activity of neurons in the inferior colliculus (IC), but the conditions that influence 5-HT neurotransmission in this region of the brain are unknown. We used in vivo voltammetry to measure extracellular 5-HT in the IC of behaving mice to address this issue. Extracellular 5-HT increased with the recovery from anesthesia, suggesting that the neuromodulation of auditory processing is correlated with the level of behavioral arousal. Awake mice were further exposed to auditory (broadband noise), visual (light) or olfactory (2,5-dihydro-2,4,5-trimethylthiazoline, TMT) stimuli, presented with food or confined in a small arena. Only the auditory stimulus or restricted movement increased the concentration of extracellular 5-HT in the IC. Changes occurred within minutes of stimulus onset, with the auditory stimulus increasing extracellular 5-HT by an average of 5% and restricted movement increasing it by an average of 14%. These findings suggest that the neuromodulation of auditory processing by 5-HT is a dynamic process that is dependent on internal state and behavioral conditions

    Extracellular ascorbate modulates glutamate dynamics: role of behavioral activation

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    <p>Abstract</p> <p>Background</p> <p>A physiological increase in extracellular ascorbate (AA), an antioxidant vitamin found throughout the striatum, elevates extracellular glutamate (GLU). To determine the role of behavioral arousal in this interaction, microdialysis was used to measure striatal GLU efflux in rats tested in either a lights-off or lights-on condition while reverse dialysis either maintained the concentration of AA at 250 μM or increased it to 1000 μM to approximate endogenous changes.</p> <p>Results</p> <p>When lights were off, both locomotion and GLU increased regardless of AA dose. In contrast, animals in the lights-on condition were behaviorally inactive, and infusion of 1000, but not 250, μM AA significantly increased extracellular GLU. Interestingly, when ambient light returned to the lights-off group, 1000 μM prolonged the GLU increase relative to the 250 μM group.</p> <p>Conclusion</p> <p>Our results not only support evidence that elevated striatal AA increases extracellular GLU but also indicate that this effect depends on behavioral state and the corresponding level of endogenous GLU release.</p

    Origin of the low critical observing temperature of the quantum anomalous Hall effect in V-doped (Bi, Sb)2Te3 film

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    The experimental realization of the quantum anomalous Hall (QAH) effect in magnetically-doped (Bi, Sb)[subscript 2]Te[subscript 3] films stands out as a landmark of modern condensed matter physics. However, ultra-low temperatures down to few tens of mK are needed to reach the quantization of Hall resistance, which is two orders of magnitude lower than the ferromagnetic phase transition temperature of the films. Here, we systematically study the band structure of V-doped (Bi, Sb)[subscript 2]Te[subscript 3] thin films by angle-resolved photoemission spectroscopy (ARPES) and show unambiguously that the bulk valence band (BVB) maximum lies higher in energy than the surface state Dirac point. Our results demonstrate clear evidence that localization of BVB carriers plays an active role and can account for the temperature discrepancy

    Equation of State of Water in the Megabar Range

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    We present some preliminary results on the equation of state (EOS) of water in a pressure regime of astrophysical interest. In the experiments, structured targets made of an aluminum step followed by a water layer are irradiated by the laser at an intensity up to 4·1014 W·cm−2 to generate a shock wave. Velocities are measured in the two materials using a VISAR interferometric diagnostic for water, and a streak camera to measure target self-emission for Al. EOS points for water are obtained with the impedance mismatch method using Al EOS as a reference. Water reflectivity was also measured

    Characterization and identification of clinically relevant microorganisms using rapid evaporative ionization mass spectrometry

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    Rapid evaporative ionization mass spectrometry (REIMS) was investigated for its suitability as a general identification system for bacteria and fungi. Strains of 28 clinically relevant bacterial species were analyzed in negative ion mode, and corresponding data was subjected to unsupervised and supervised multivariate statistical analyses. The created supervised model yielded correct cross-validation results of 95.9%, 97.8%, and 100% on species, genus, and Gram-stain level, respectively. These results were not affected by the resolution of the mass spectral data. Blind identification tests were performed for strains cultured on different culture media and analyzed using different instrumental platforms which led to 97.8–100% correct identification. Seven different Escherichia coli strains were subjected to different culture conditions and were distinguishable with 88% accuracy. In addition, the technique proved suitable to distinguish five pathogenic Candida species with 98.8% accuracy without any further modification to the experimental workflow. These results prove that REIMS is sufficiently specific to serve as a culture condition-independent tool for the identification and characterization of microorganisms

    Sub-Second Dopamine Detection in Human Striatum

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    Fast-scan cyclic voltammetry at carbon fiber microelectrodes allows rapid (sub-second) measurements of dopamine release in behaving animals. Herein, we report the modification of existing technology and demonstrate the feasibility of making sub-second measurements of dopamine release in the caudate nucleus of a human subject during brain surgery. First, we describe the modification of our electrodes that allow for measurements to be made in a human brain. Next, we demonstrate in vitro and in vivo, that our modified electrodes can measure stimulated dopamine release in a rat brain equivalently to previously determined rodent electrodes. Finally, we demonstrate acute measurements of dopamine release in the caudate of a human patient during DBS electrode implantation surgery. The data generated are highly amenable for future work investigating the relationship between dopamine levels and important decision variables in human decision-making tasks

    Sodium-Dependent Vitamin C Transporter 2 (SVCT2) Expression and Activity in Brain Capillary Endothelial Cells after Transient Ischemia in Mice

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    Expression and transport activity of Sodium-dependent Vitamin C Transporter 2 (SVCT2) was shown in various tissues and organs. Vitamin C was shown to be cerebroprotective in several animal models of stroke. Data on expression, localization and transport activity of SVCT2 after cerebral ischemia, however, has been scarce so far. Thus, we studied the expression of SVCT2 after middle cerebral artery occlusion (MCAO) in mice by immunohistochemistry. We found an upregulation of SVCT2 after stroke. Co-stainings with Occludin, Von-Willebrand Factor and CD34 demonstrated localization of SVCT2 in brain capillary endothelial cells in the ischemic area after stroke. Time-course analyses of SVCT2 expression by immunohistochemistry and western blots showed upregulation in the subacute phase of 2–5 days. Radioactive uptake assays using 14C-labelled ascorbic acid showed a significant increase of ascorbic acid uptake into the brain after stroke. Taken together, these results provide evidence for the expression and transport activity of SVCT2 in brain capillary endothelial cells after transient ischemia in mice. These results may lead to the development of novel neuroprotective strategies in stroke therapy

    Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of huntington's disease

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    Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI), as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. © 2013 Rattray et al
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