Neuronal and astroglial correlates underlying spatiotemporal Intrinsic Optical Signal in the rat hippocampal slice

Widely used for mapping afferent activated brain areas in vivo, the label-free intrinsic optical signal (IOS) is mainly ascribed to blood volume changes subsequent to glial glutamate uptake. By contrast, IOS imaged in vitro is generally attributed to neuronal and glial cell swelling, however the relative contribution of different cell types and molecular players remained largely unknown. We characterized IOS to Schaffer collateral stimulation in the rat hippocampal slice using a 464-element photodiode-array device that enables IOS monitoring at 0.6 ms time-resolution in combination with simultaneous field potential recordings. We used brief half-maximal stimuli by applying a medium intensity 50 Volt-stimulus train within 50 ms (20 Hz). IOS was primarily observed in the str. pyramidale and proximal region of the str. radiatum of the hippocampus. It was eliminated by tetrodotoxin blockade of voltage-gated Na+ channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin. We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg2+-independent astroglial N-methyl-D-aspartate receptors. Under control conditions, role for neuronal K+/Cl- cotransporter KCC2, but not for glial Na+/K+/Cl- cotransporter NKCC1 was observed. Slight enhancement and inhibition of IOS through non-specific Cl- and volume-regulated anion channels, respectively, were also depicted. High-frequency IOS imaging, evoked by brief afferent stimulation in brain slices provide a new paradigm for studying mechanisms underlying IOS genesis. Major players disclosed this way imply that spatiotemporal IOS reflects glutamatergic neuronal activation and astroglial response, as observed within the hippocampus. Our model may help to better interpret in vivo IOS and support diagnosis in the future

Adsorption of Methylene Fluoride and Methylene Chloride at the Surface of Ice under Tropospheric Conditions: A Grand Canonical Monte Carlo Simulation Study

The adsorption of two halogenated methane derivatives, namely, methylene fluoride and methylene chloride, at the surface of Ih ice is studied by grand canonical Monte Carlo simulations under tropospheric conditions. The adsorption isotherms of the two molecules, differing only in the halogen atom type, are found to be markedly different from each other. Thus, while methylene fluoride exhibits multilayer adsorption and its adsorption isotherm belongs to class II according to the IUPAC convention, methylene chloride does not show considerable adsorption at the ice surface, as its condensation well precedes the saturation of even the first adsorbed molecular layer. Interestingly, both the surface orientation and the binding energy of the two types of adsorbed molecules are rather similar to each other; first layer molecules form one single hydrogen bond with the dangling OH groups of the ice surface. The strong differences in the adsorption behavior of methylene fluoride and methylene chloride are traced back to the different cohesions in the liquid phase and, hence, to the strongly different boiling points of the two molecules

Polyamidoamine dendrimer impairs mitochondrial oxidation in brain tissue

Background: The potential nanocarrier polyamidoamine (PAMAM) generation 5 (G5-NH2) dendrimer has been shown to evoke lasting neuronal depolarization and cell death in a concentration-dependent manner. In this study we explored the early progression of G5-NH2 action in brain tissue on neuronal and astroglial cells.Results: In order to describe early mechanisms of G5-NH2 dendrimer action in brain tissue we assessed G5-NH2 trafficking, free intracellular Ca2+ and mitochondrial membrane potential (ΨMITO) changes in the rat hippocampal slice by microfluorimetry. With the help of fluorescent dye conjugated G5-NH2, we observed predominant appearance of the dendrimer in the plasma membrane of pyramidal neurons and glial cells within 30 min. Under this condition, G5-NH2 evoked robust intracellular Ca2+ enhancements and ΨMITO depolarization both in pyramidal neurons and astroglial cells. Intracellular Ca2+ enhancements clearly preceded ΨMITO depolarization in astroglial cells. Comparing activation dynamics, neurons and glia showed prevalence of lasting and transient ΨMITO depolarization, respectively. Transient as opposed to lasting ΨMITO changes to short-term G5-NH2 application suggested better survival of astroglia, as observed in the CA3 stratum radiatum area. We also showed that direct effect of G5-NH2 on astroglial ΨMITO was significantly enhanced by neuron-astroglia interaction, subsequent to G5-NH2 evoked neuronal activation.Conclusion: These findings indicate that the interaction of the PAMAM dendrimer with the plasma membrane leads to robust activation of neurons and astroglial cells, leading to mitochondrial depolarization. Distinguishable dynamics of mitochondrial depolarization in neurons and astroglia suggest that the enhanced mitochondrial depolarization followed by impaired oxidative metabolism of neurons may be the primary basis of neurotoxicity. © 2013 Nyitrai et al.; licensee BioMed Central Ltd

Folyadék és amorf szerkezetű anyagok vizsgálata diffrakcióval és számítógépes modellezéssel = Investigations of liquid and amorphous structures by diffraction and computer modelling methods

Eredeti pályázatunknak megfelelően elsősorban folyadékok szerkezetét vizsgáltuk (elsősorban röntgen)diffrakciós módszerrel és az azt követő Reverse Monte Carlo (RMC) modellezéssel. Az elnyert támogatás a világ legnagyobb teljesítményű szinktrotronforrásánál, a SPring-8-nél (Hyogo, Japán) végzett (nagyenergiás) röntgendiffrakciós kísérleteket tett lehetővé. Meghatároztuk nagynyomású, szobahőmérsékletű folyékony (szuperkritikus állapotban lévő) oxigén és nitrogén lokális szerkezetét; úgy találtuk, hogy a szomszédos molekulák párhuzamos beállása mellett az 'X'-alakú konformáció is gyakori. Azonosítottuk az ón-tetrajodid folyadékfázisát mint azt az anyagot, amelyben a legnagyobb arányban fordulnak elő a szabályos tetraéder alakú molekulák 'csúcs-lap' (azaz 'Apollo') típusú illeszkedése. Az XCl4 szabályos tetraéder alakú molekulákból álló folyadékokban (X: C, Si, Ge, Sn) a vártnál (valamint az eddigiekben javasolthoz képest) lényegesebb hosszabb, néhány nanométerre kiterjedő orientációs rendezettséget találtunk. | According to our original project plan, we've investigated primarily liquid structures, using (primarily X-ray) diffraction methods and subsequent Reverse Monte Carlo modeling. The support awarded made it possible to carry out (high energy) X-ray diffraction experiments at the world's most powerful synchrotron source, SPring-8 (Hyogo, Japan). We have determined the local structure of high-pressure, room temperature liquid (supercritical fluid) oxygen and nitrogen; it was found that apart from the parallel configuration, neighboring molecules frequently choose 'X'-shaped mutual orientations. We have identified liquid tin tetraiodoide as the material which contains the highest ratio of 'corner-to-face' (or so-called 'Apollo') type conformations of molecules with perfect tetrahedral shape. In liquids of XCl4 (perfect tetrahedral) molecules (X: C, Si, Ge, Sn) a rather long (much longer than expected and than had been suggested before), nanometer range orientational ordering of molecules

Synthesis and enantiomeric recognition studies of a novel 5,5-dioxophenothiazine-1,9 bis(thiourea) containing glucopyranosyl groups

A novel optically active 5,5-dioxophenothiazine-1,9 bis(thiourea) containing glucopyranosyl groups was synthesized and its enantiomeric recognition properties were examined towards the enantiomers of tetrabutylammonium salts of chiral α-hydroxy and N-protected α-amino acids using UV–vis spectroscopy

Local motifs in GeS2_2-Ga2_2S3_3 glasses

The structure of (GeS$_2$)$_{0.75}$(Ga$_2$S$_3$)$_{0.25}$ and (GeS$_2$)$_{0.83}$(Ga$_2$S$_3$)$_{0.17}$ glasses was investigated by Raman scattering, high energy X-ray diffraction and extended X-ray absorption fine structure (EXAFS) measurements at the Ga and Ge K-edges. The reverse Monte Carlo simulation technique (RMC) was used to obtain structural models compatible with diffraction and EXAFS datasets. It was found that the coordination number of Ga is close to four. While Ge atoms have only S neighbors, Ga binds to S as well as to Ga atoms showing a violation of chemical ordering in GeS$_2$-Ga$_2$S$_3$ glasses. Analysis of the corner- and edge-sharing between [GeS$_{4/2}$] units revealed that about 30% of germanium atoms participate in the edge-shared tetrahedra.Comment: 23 pages, 7 figures, accepted for publication in Journal of Alloys and Compound

Appearance of fast astrocytic component in voltage-sensitive dye imaging of neural activity.

BACKGROUND: Voltage-sensitive dye (VSD) imaging and intrinsic optical signals (IOS) are widely used methods for monitoring spatiotemporal neural activity in extensive networks. In spite of that, identification of their major cellular and molecular components has not been concluded so far. RESULTS: We addressed these issues by imaging spatiotemporal spreading of IOS and VSD transients initiated by Schaffer collateral stimulation in rat hippocampal slices with temporal resolution comparable to standard field potential recordings using a 464-element photodiode array. By exploring the potential neuronal and astroglial molecular players in VSD and IOS generation, we identified multiple astrocytic mechanisms that significantly contribute to the VSD signal, in addition to the expected neuronal targets. Glutamate clearance through the astroglial glutamate transporter EAAT2 has been shown to be a significant player in VSD generation within a very short (<5 ms) time-scale, indicating that astrocytes do contribute to the development of spatiotemporal VSD transients previously thought to be essentially neuronal. In addition, non-specific anion channels, astroglial K(+) clearance through Kir4.1 channel and astroglial Na(+)/K(+) ATPase also contribute to IOS and VSD transients. CONCLUSION: VSD imaging cannot be considered as a spatially extended field potential measurement with predominantly neuronal origin, instead it also reflects a fast communication between neurons and astrocytes

Adsorption of Fluorinated Methane Derivatives at the Surface of Ice under Tropospheric Conditions, As Seen from Grand Canonical Monte Carlo Simulations

The adsorption of the fluorinated methane derivatives, CHnF4-n, at the (0001) surface of Ih ice is studied by grand canonical Monte Carlo computer simulation at the tropospheric temperature of 200 K. It is found that CH4 and CF4 adsorbs rather weakly, while CH3F, CH2F2, and CHF3 exhibit multilayer adsorption. The vapor phase of CH4 and CF4 turns out to be rather dense, in accordance with the fact that CF4 is already rather close to, while CH4 is already above, its critical point. Adsorbed CH3F molecules, being in contact with the ice phase, turn with their H atoms toward the ice surface, forming several weak, C-H donated hydrogen bonds with the surface water molecules. By contrast, CH2F2 and CHF3 molecules are found to turn at least one of their F atoms toward the ice phase, forming strong, O-H donated hydrogen bonds with surface waters, in accordance with former infrared (IR) spectroscopy data. Once all hydrogen-bonding positions are occupied, the first molecular layer of these molecules is not yet saturated. Thus, further molecules can be adsorbed in contact with the ice phase, but without forming hydrogen bonds with it