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Frank, Thomas
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Frank, Thomas
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Frank, Thomas
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Frank, T.
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2009Journal Article Research Paper [["dc.bibliographiccitation.firstpage","4483"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","4488"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:47:32Z"],["dc.date.available","2017-09-07T11:47:32Z"],["dc.date.issued","2009"],["dc.description.abstract","Sound coding at hair cell ribbon synapses is tightly regulated by Ca2+. Here, we used patch-clamp, fast confocal Ca2+ imaging and modeling to characterize synaptic Ca2+ signaling in cochlear inner hair cells (IHCs) of hearing mice. Submicrometer fluorescence hotspots built up and collapsed at the base of IHCs within a few milliseconds of stimulus onset and cessation. They most likely represented Ca2+ microdomains arising from synaptic Ca2+ influx through Ca(V)1.3 channels. Synaptic Ca2+ microdomains varied substantially in amplitude and voltage dependence even within single IHCs. Testing putative mechanisms for the heterogeneity of Ca2+ signaling, we found the amplitude variability unchanged when blocking mitochondrial Ca2+ uptake or Ca2+-induced Ca2+ release, buffering cytosolic Ca2+ by millimolar concentrations of EGTA, or elevating the Ca2+ channel open probability by the dihydropyridine agonist BayK8644. However, we observed substantial variability also for the fluorescence of immunolabeled Ca(V)1.3 Ca2+ channel clusters. Moreover, the Ca2+ microdomain amplitude correlated positively with the size of the corresponding synaptic ribbon. Ribbon size, previously suggested to scale with the number of synaptic Ca2+ channels, was approximated by using fluorescent peptide labeling. We propose that IHCs adjust the number and the gating of Ca(V)1.3 channels at their active zones to diversify their transmitter release rates."],["dc.identifier.doi","10.1073/pnas.0813213106"],["dc.identifier.gro","3143138"],["dc.identifier.isi","000264278800077"],["dc.identifier.pmid","19246382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/619"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Mechanisms contributing to synaptic Ca2+ signals and their heterogeneity in hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2010Journal Article Research Paper [["dc.bibliographiccitation.firstpage","724"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","738"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Pangrsic, Tina"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Fetjova, Anna"],["dc.contributor.author","Gundelfinger, Eckart D."],["dc.contributor.author","Liberman, M. Charles"],["dc.contributor.author","Harke, Benjamin"],["dc.contributor.author","Bryan, Keith E."],["dc.contributor.author","Lee, Amy"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:45:13Z"],["dc.date.available","2017-09-07T11:45:13Z"],["dc.date.issued","2010"],["dc.description.abstract","At the presynaptic active zone, Ca2+ influx triggers fusion of synaptic vesicles. It is not well understood how Ca2+ channel clustering and synaptic vesicle docking are organized. Here, we studied structure and function of hair cell ribbon synapses following genetic disruption of the presynaptic scaffold protein Bassoon. Mutant synapses-mostly lacking the ribbon-showed a reduction in membrane-proximal vesicles, with ribbonless synapses affected more than ribbon-occupied synapses. Ca2+ channels were also fewer at mutant synapses and appeared in abnormally shaped clusters. Ribbon absence reduced Ca2+ channel numbers at mutant and wildtype synapses. Fast and sustained exocytosis was reduced, notwithstanding normal coupling of the remaining Ca2+ channels to exocytosis. In vitro recordings revealed a slight impairment of vesicle replenishment. Mechanistic modeling of the in vivo data independently supported morphological and functional in vitro findings. We conclude that Bassoon and the ribbon (1) create a large number of release sites by organizing Ca2+ channels and vesicles, and (2) promote vesicle replenishment."],["dc.identifier.doi","10.1016/j.neuron.2010.10.027"],["dc.identifier.gro","3142827"],["dc.identifier.isi","000285079500011"],["dc.identifier.pmid","21092861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/274"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0896-6273"],["dc.title","Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2010Conference Abstract [["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Chapochnikov, Nikolai M."],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-11-07T08:47:12Z"],["dc.date.available","2018-11-07T08:47:12Z"],["dc.date.issued","2010"],["dc.format.extent","576A"],["dc.identifier.isi","000208762005379"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20890"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.publisher.place","Cambridge"],["dc.relation.issn","0006-3495"],["dc.title","Optical Analysis of Calcium Channels at the First Auditory Synapse"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details WOS2010Journal Article [["dc.bibliographiccitation.firstpage","1202"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Pangrsic, Tina"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Fejtova, Anna"],["dc.contributor.author","Gundelfinger, Eckart D."],["dc.contributor.author","Liberman, M. Charles"],["dc.contributor.author","Harke, Benjamin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2022-03-01T11:45:20Z"],["dc.date.available","2022-03-01T11:45:20Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/j.neuron.2010.12.020"],["dc.identifier.pii","S0896627310010433"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103294"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0896-6273"],["dc.title","Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]Details DOI2009Journal Article [["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.lastpage","1"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Chapochnikov, Nikolai M."],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2011-04-12T13:30:30Z"],["dc.date.accessioned","2021-10-11T11:34:47Z"],["dc.date.available","2011-04-12T13:30:30Z"],["dc.date.available","2021-10-11T11:34:47Z"],["dc.date.issued","2009"],["dc.identifier.citation","Chapochnikov, Nikolai M; Frank, Thomas; Strenzke, Nicola; Neef, Andreas; Khimich, Darina; Egner, Alexander; Wolf, Fred; Moser, Tobias (2009): Modeling the origin of functional heterogeneity among auditory nerve fibers - BMC Neuroscience, Vol. 10, Nr. Suppl 1, p. P220-"],["dc.identifier.doi","10.1186/1471-2202-10-S1-P220"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6101"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90701"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","http://goedoc.uni-goettingen.de/licenses"],["dc.subject","heterogeneity; auditory nerve fibers"],["dc.subject.ddc","530"],["dc.subject.ddc","573"],["dc.subject.ddc","573.8"],["dc.subject.ddc","612"],["dc.subject.ddc","612.8"],["dc.title","Modeling the origin of functional heterogeneity among auditory nerve fibers"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI