Investigating the Calcium Signaling at Ribbon Synapses

Frank, Thomas

dc.contributor.advisor	Moser, Tobias Dr.	de
dc.contributor.author	Frank, Thomas	de
dc.date.accessioned	2010-05-11T06:54:02Z	de
dc.date.accessioned	2013-01-18T14:29:37Z	de
dc.date.available	2013-01-30T23:50:20Z	de
dc.date.issued	2010-05-11	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0006-B50F-B	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3319
dc.description.abstract	Mittels "whole-cell patch-clamp" und schneller, konfokaler Ca2+-Bildgebung werden lokalisierte Ca2+ Signale an einzelnen Bändersynapsen reifer innerer Haarzellen der Maus beschrieben. Des weiteren wird die Abhängigkeit dieser Signale von einer Reihe unterschiedlicher Parameter, inklusive Ca2+-Pufferung, Ca2+-induzierte Ca2+-Freisetzung, und Lage in der Cochlea untersucht. Sowohl die Amplitude als auch die Spannungsabhängigkeit der Ca2+-Signale zeigt ausgeprägte intrazelluläre Heterogeneität über unterschiedliche Synapsen hinweg. In Bezug auf die Amplitudenvariation erscheint eine unterschiedliche Anzahl von Ca2+-Kanälen als wahrscheinliche Erklärung. Zuletzt werden mögliche Auswirkungen der unterschiedlichen präsynaptischen Ca2+-Kanal-Anzahl auf die Antworteigenschaften postsynaptischer Spiral-Ganglion-Neurone theoretisch untersucht sowie diskutiert.	de
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	de
dc.title	Investigating the Calcium Signaling at Ribbon Synapses	de
dc.type	doctoralThesis	de
dc.title.translated	Untersuchung von Kalzium-Signalen an Bändersynapsesn	de
dc.contributor.referee	Schild, Detlev Prof. Dr.	de
dc.date.examination	2010-04-30	de
dc.subject.dnb	570 Biowissenschaften	de
dc.subject.dnb	Biologie	de
dc.description.abstracteng	Using whole-cell patch-clamp and fast confocal Ca2+ imaging we show that localized Ca2+ influx sites exist at ribbon synapses in mature inner hair cells of the mouse. Spot detection measurements at these fluorescent hot-spots allowed their precise kinetic characterization, revealing rapid build-up and cessation within few milliseconds. We find that these Ca2+ microdomains represent Ca2+ influx through presynaptic clusters of CaV1.3 channels and that Ca2+-induced Ca2+ release does not play a role in shaping these responses. They were ob-served under a range of different Ca2+ buffering conditions including the presence of endogenous buffers. A combined model of Ca2+ reaction-diffusion and imaging predicted the experimentally observed responses reasonably well, under a set of different conditions. The amplitude and the voltage-dependence of these Ca2+ microdomains showed pronounced variability across individual synapses within single cells. A number of control experiments indicate that this variability is largely of biological origin and only to a minor degree introduced by the experimental observations. Different manipulations, including interference with Ca2+ buffering, Ca2+ channel gating and Ca2+ homeostasis left the variability of Ca2+ microdomain amplitudes unchanged. However, we found substantial variability in the antigen-content between presynaptic Ca2+ channel clusters as well as a positive correlation between the size of the active zone as indicated by a size estimate of the synaptic ribbon and the amplitude of its associated Ca2+ microdomain signal. We propose that individual active zones within a given hair cell differ in the number and gating of Ca2+ channels, resulting in different amplitudes and voltage-dependencies of synaptic Ca2+ influx. These specializations provide two levels of regulation to d ifferentially adjust synaptic transfer characteristics at individual synapses. Im-plementation of our results into a model of the inner hair cell to auditory nerve fiber synapse further suggests a strong impact of presynaptic Ca2+ channel number on the firing characteris-tics of the postsynaptic auditory nerve fibers and thus sound coding. We apply this technique to investigate presynaptic function at different tonotopic locations, revealing that unlike in other species mice do not adjust the characteristics but rather the number of IHC ribbon synapses in a frequency-dependent manner.	de
dc.subject.topic	Molecular Biology & Neurosciences Program	de
dc.subject.ger	Kalzium-Mikrodomäne	de
dc.subject.ger	Mikroskopie	de
dc.subject.ger	Bändersynapse	de
dc.subject.ger	Haarzelle	de
dc.subject.ger	auditorisches System	de
dc.subject.ger	Modellierung	de
dc.subject.ger	Kodierung	de
dc.subject.eng	calcium microdomain	de
dc.subject.eng	imaging	de
dc.subject.eng	ribbon synapse	de
dc.subject.eng	hair cell	de
dc.subject.eng	auditory system	de
dc.subject.eng	modeling	de
dc.subject.eng	coding	de
dc.subject.bk	42.15	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-2453-0	de
dc.identifier.purl	webdoc-2453	de
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	WA 000: Biologie	de
dc.identifier.ppn	635398117	de

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1116]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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