6,251 research outputs found

    Gesunder Menschenverstand über die Kunst Völker zu beglücken : eine Morgengabe allen Völkern, Volksregierungen, Priestern, Lehrern, Eltern und Freunden der gegenwärtigen und künftigen Generationen

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    dargereicht ... von Andr. MoserImpressum: Gedruckt im Lande der Freiheit für das Jahr der Gegenwart und die Zeit der Zukunf

    Termination Proofs in the Dependency Pair Framework May Induce Multiple Recursive Derivational Complexity

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    We study the complexity of rewrite systems shown terminating via the dependency pair framework using processors for reduction pairs, dependency graphs, or the subterm criterion. The complexity of such systems is bounded by a multiple recursive function, provided the complexity induced by the employed base techniques is at most multiple recursive. Moreover this upper bound is tight

    Stylos kai edraiōma tēs ekklēsias, sive, Dissertatio de iustificatione hominis

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    quam ... sub praesidio ... Ioh. Henrici Heideggeri ... placido eruditorum examini subiicit Andreas Steinerus, Vitod. author & respondens, ad diem Octobris loco horisque solitisDiss. Hohe Schule Zürich, 167

    Karoline von Sonneburg oder die Maskerade im Königssaale : Ein dramatisches Gemälde / von Andreas Moser

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    Enth. Kupferst. von L. Maillar und S. MansfeldFrontispiz in Seitenzählung enthVorlageform des Erscheinungsvermerks: Wien, 1797. Bey Christoph Peter RehmFrontispiz (Kupferst.

    Mechanisms underlying the temporal precision of sound coding at the inner hair cell ribbon synapse

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    Our auditory system is capable of perceiving the azimuthal location of a low frequency sound source with a precision of a few degrees. This requires the auditory system to detect time differences in sound arrival between the two ears down to tens of microseconds. The detection of these interaural time differences relies on network computation by auditory brainstem neurons sharpening the temporal precision of the afferent signals. Nevertheless, the system requires the hair cell synapse to encode sound with the highest possible temporal acuity. In mammals, each auditory nerve fibre receives input from only one inner hair cell (IHC) synapse. Hence, this single synapse determines the temporal precision of the fibre. As if this was not enough of a challenge, the auditory system is also capable of maintaining such high temporal fidelity with acoustic signals that vary greatly in their intensity. Recent research has started to uncover the cellular basis of sound coding. Functional and structural descriptions of synaptic vesicle pools and estimates for the number of Ca2+ channels at the ribbon synapse have been obtained, as have insights into how the receptor potential couples to the release of synaptic vesicles. Here, we review current concepts about the mechanisms that control the timing of transmitter release in inner hair cells of the cochlea

    Ca<sub>V</sub>1.3 Channels Are Essential for Development and Presynaptic Activity of Cochlear Inner Hair Cells

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    Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. During early development, afferent synaptic transmission is triggered by spontaneous Ca2+spikes of IHCs, which are under efferent cholinergic control. Around the onset of hearing, large-conductance Ca2+-activated K+channels are acquired, and Ca2+spikes as well as the cholinergic innervation are lost.Here, we performed patch-clamp measurements in IHCs of mice lacking the CaV1.3 channel (CaV1.3-/-) to investigate the role of this prevailing voltage-gated Ca2+channel in IHC development and synaptic function. The small Ca2+current remaining in IHCs from 3-week-old CaV1.3-/-mice was mainly mediated by L-type Ca2+channels, because it was sensitive to dihydropyridines but resistant to inhibitors of non-L-type Ca2+channels such as ω-conotoxins GVIA and MVIIC and SNX-482. Depolarization induced only marginal exocytosis in CaV1.3-/-IHC, which was solely mediated by L-type Ca2+channels, whereas robust exocytic responses were elicited by photolysis of caged Ca2+. Secretion triggered by short depolarizations was reduced proportionally to the Ca2+current, suggesting that the coupling of the remaining channels to exocytosis was unchanged.CaV1.3-/-IHCs lacked the Ca2+action potentials and displayed a complex developmental failure. Most strikingly, we observed a continued presence of efferent cholinergic synaptic transmission and a lack of functional large-conductance Ca2+-activated K+channels up to 4 weeks after birth. We conclude that CaV1.3 channels are essential for normal hair cell development and synaptic transmission.</jats:p

    Measurements of membrane patch capacitance using a software-based lock-in system

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    On-cell patch-clamp capacitance measurements can resolve the fusion of individual vesicles to a membrane patch and the accompanying dilation of the fusion pore. So far, these measurements have used a patch-clamp amplifier in combination with a hardware lock-in amplifier. Usually, solely the capacitance and conductance outputs of hardware lock-in amplifiers were recorded, which needed to be filtered rather heavily to suppress spectral components at the stimulus frequency. Therefore, the temporal resolution was limited, and information carried in the patch current was not utilized. In this paper, we describe an alternative and more versatile approach for measuring patch capacitance and conductance, using a digitally controlled patch-clamp amplifier. The software lock-in system showed better bandwidth and identical signal-to-noise performance needing less instrumentation. High temporal resolution measurements on patches of chromaffin cells showed that vesicle fission can be completed in only tens of microseconds. Capacitance calculation based on the patch current allows for straightforward offline phase correction. Moreover, the close inspection of direct current for the first time revealed small current changes accompanying the fusion and fission of large secretory vesicles, promising new insights into the vesicles' membrane properties. A practical guide to high-resolution on-cell patch-clamp capacitance measurements using the software lock-in is provided

    Few Ca(V)1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse

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    Hearing relies on faithful sound coding at hair cell ribbon synapses, which use Ca2+-triggered glutamate release to signal with submillisecond precision. Here, we investigated stimulus-secretion coupling at mammalian inner hair cell (IHC) synapses to explore the mechanisms underlying this high temporal fidelity. Using nonstationary fluctuation analysis on Ca2+ tail currents, we estimate that IHCs contain similar to 1700 Ca2+ channels, mainly of Ca(V)1.3 type. We show by immunohistochemistry that the Ca(V)1.3 Ca2+ channels are localized preferentially at the ribbon-type active zones of IHCs. We argue that each active zone holds similar to 80 Ca2+ channels, of which probably < 10 open simultaneously during physiological stimulation. We then manipulated the Ca2+ current by primarily changing single-channel current or open-channel number. Effects on exocytosis of the readily releasable vesicle pool (RRP) were monitored by membrane capacitance recordings. Consistent with the high intrinsic Ca2+ cooperativity of exocytosis, RRP exocytosis changed nonlinearly with the Ca2+ current when varying the single-channel current. In contrast, the apparent Ca2+ cooperativity of RRP exocytosis was close to unity when primarily manipulating the number of open channels. Our findings suggest a Ca2+ channel-release site coupling in which few nearby Ca(V)1.3 channels impose high nanodomain [Ca2+] on release sites in IHCs during physiological stimulation. We postulate that the IHC ribbon synapse uses this Ca2+ nanodomain control of exocytosis to signal with high temporal precision already at low sound intensities
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