1,567 research outputs found

    Overview and progress on the Laser Interferometer Space Antenna mission

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    At a Lorentz Center workshop, Chiara Caprini, Antoine Petiteau and Elena Maria Rossi gave a series of presentations about the Laser Interferometer Space Antenna (LISA) mission, the instrument, and the associated science in cosmology and astrophysics

    Forskolin and protein kinase inhibitors differentially affect hair cell potassium currents and transmitter release at the cytoneural junction in the isolated frog labyrinth

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    The post-transductional elaboration of sensory input at the frog semicircular canal has been studied by correlating the effects of drugs that interfere with phosphorylation processes on: (i) potassium conductances in isolated hair cell and (ii) transmitter release at the cytoneural junction in the intact labyrinth. At hair cells, delayed potassium currents (IKD) undergo voltage- and time-dependent inactivation; inactivation removal requires ATP, is sensitive to kinase blockade, but is unaffected by exogenous application of cyclic nucleotides. We report here that forskolin, an activator of endogenous adenylyl cyclase, enhances IKD inactivation removal in isolated hair cells, but produces an overall decrease in IKD amplitude consistent with the direct blocking action of the drug on several families of K channels. In the intact labyrinth, forskolin enhances transmitter release, consistent with such depression of K conductances. Kinase blockers â H-89 and KT5823 â have been shown to reduce IKD inactivation removal and IKD amplitude at isolated hair cells. In the labyrinth, the effects of these drugs on junctional activity are quite variable, with predominant inhibition of transmitter release, rather than the enhancement expected from the impairment of K currents. The overall action of forskolin and kinase inhibitors on K conductances is similar (depression), but they have opposite effects on transmitter release: this indicates that some intermediate steps between the bioelectric control of hair cell membrane potential and transmitter release are affected in opposite ways and therefore are presumably regulated by protein phosphorylation

    Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission.

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    At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot be studied at the intact semicircular canal. To circumvent the problem, we combined patch-clamp recordings at the isolated hair cell and electrophysiological recordings at the cytoneural junction in the intact preparation. At isolated hair cells, the K channel blocker TEA is shown to block a fraction of total voltage-dependent K-conductance (IKD) that depends on TEA concentration but not on membrane potential (Vm). Considering the bioelectric properties of the hair cell, as previously characterized by this lab, a fixed fractional block of IKD is shown to induce a relatively fixed shift in Vm, provided it lies in the range -30 to -10 mV. The same concentrations of TEA were applied to the intact labyrinth while recording from single afferent fibers of the posterior canal, at rest and during mechanical stimulation. At the peak of stimulation, TEA produced increases in mEPSP rate that were linearly related to the shifts produced by the same TEA concentrations (0.1-3 mM) in hair cell Vm (0.7-5 mV), with a slope of 29.8 Hz/mV. The membrane potential of the hair cell is not linearly related to receptor conductance, so that the slope of quantal release vs. receptor conductance depends on the prevailing Vm (19.8 Hz/nS at -20 mV; 11 Hz/nS at -10 mV). Changes in mEPSP peak size were negligible at rest as well as during stimulation. Since ample spatial summation of mEPSPs occurs at the afferent terminal and threshold-governed spike firing is intrinsically nonlinear, the observed increases in mEPSP frequency, though not very large, may suffice to trigger afferent spike discharge

    Synergies between Gaia and LISA missions for Galactic multi-messenger studies

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    Ultra-short period Galactic binaries are unique multi-messenger tracers of the Milky Way. They can be detected in large numbers through electromagnetic radiation by Gaia and through gravitational waves by the upcoming LISA mission. First, we revise the current census of known multi-messenger Galactic binaries by computing their GW signals using updated distances from the Gaia Data Release 2. Our work confirms thirteen guaranteed multi-messenger sources: nine AM CVns, three detached double white dwarfs (DWD) and one hot subdwarf. Next, we forecast the detection prospects for DWDs with both Gaia and LISA using a binary population synthesis technique. We predict respectively hundreds and tens of thousands detections by Gaia and LISA, with an overlap of several tens. We show that synergies between Gaia and LISA observations of DWDs allow the study of the Milky Way baryonic structure. The success of this synergy is due to LISA's ability to localise binaries through virtually the whole Galactic plane, thus mapping its shape. While observations of LISA's electromagnetic counterparts observed by Gaia yield the information on their motion; tracing the underlying total enclosed mass. We envisage that multi-messenger observations will ensure the best science return of the LISA mission for Galactic studies

    Pre- and Postsynaptic Effects of Glutamate in the Frog Labyrinth

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    The role of glutamate in quantal release at the cytoneural junction was examined by measuring mEPSPs and afferent spikes at the posterior canal in the intact frog labyrinth. Release was enhanced by exogenous glutamate, or DL-TBOA, a blocker of glutamate reuptake. Conversely, drugs acting on ionotropic glutamate receptors did not affect release; the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) blocker CNQX decreased mEPSP size in a dose-dependent manner; the NMDA-R blocker p-AP5 at concentrations <200 mu M did not affect mEPSP size, either in the presence or absence of Mg and glycine. In isolated hair cells, glutamate did not modify Ca currents. Instead, it systematically reduced the compound delayed potassium current, IKD, whereas the metabotropic glutamate receptor (mGluR)-II inverse agonist, (2S)-2-amino-2-[(1S,2S)2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495), increased it. Given mGluR-II decrease cAMP production, these finding are consistent with the reported sensitivity of IKD to protein kinase A (PKA)mediated phosphorylation. LY341495 also enhanced transmitter release, presumably through phosphorylation-mediated facilitation of the release machinery. The observed enhancement of release by glutamate confirms previous literature data, and can be attributed to activation of mGluR-I that promotes Ca release from intracellular stores. Glutamate-induced reduction in the repolarizing IKD may contribute to facilitation of release. Overall, glutamate exerts both a positive feedback action on mGluR-I, through activation of the phospholipase C (PLC)/IP3 path, and the negative feedback, by interfering with substrate phosphorylation through G(i/0)-coupled mGluRs-II/III. The positive feedback prevails, which may explain the increase in overall rates of release observed during mechanical stimulation (symmetrical in the excitatory and inhibitory directions). The negative feedback may protect the junction from over-activation. (C) 2018 The Author(s). Published by Elsevier Ltd on behalf IBRO

    Constraining the Milky Way potential with Double White Dwarfs

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    International audienceThe upcoming LISA mission is the only experiment that will allow us to studythe Milky Way's structure using gravitational wave signals from Galactic doublewhite dwarfs (DWDs). The total number of expected detections exceeds 10510^5.Furthermore, up to a hundred DWDs can be simultaneously detected in bothgravitational and optical radiation (e.g. with Gaia and LSST as eclipsing),making DWDs ideal sources for performing a multi-messenger tomography of theGalaxy. We show that LISA will detect DWDs everywhere, mapping also theopposite side of the Galaxy. This complete coverage will: (1) provide preciseand unbiased constraints on the scale radii of the Milky Way's bulge and disc,and (2) allow us to compute the rotation curve and derive competitive estimatesfor the bulge and disc masses, when combining gravitational wave and opticalobservations

    Multi-messenger study of the Milky Way with LISA, Gaia and LSST

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    Ultra-short period double white dwarf (DWD) binaries are unique multi-messenger tracers of the Milky Way. They can be detected in large numbers through electromagnetic radiation by Gaia and through gravitational waves by the upcoming LISA mission. I will show that the synergies between gravitational waves and optical observations of DWDs allow the study of the Milky Way baryonic structure. The success of this synergy is due to LISA's ability to localise binaries through virtually the whole Galactic plane; thus mapping its shape; while Gaia observations yield the motion of stars; tracing the underlying total enclosed mass
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