Frank, Thomas

[["dc.bibliographiccitation.firstpage","4456"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","4467"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Takago, Hideki"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Fejtova, Anna"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Strenzke, Nicola"],["dc.date.accessioned","2017-09-07T11:47:46Z"],["dc.date.available","2017-09-07T11:47:46Z"],["dc.date.issued","2013"],["dc.description.abstract","Inner hair cells (IHCs) of the cochlea use ribbon synapses to transmit auditory information faithfully to spiral ganglion neurons (SGNs). In the present study, we used genetic disruption of the presynaptic scaffold protein bassoon in mice to manipulate the morphology and function of the IHC synapse. Although partial-deletion mutants lacking functional bassoon (Bsn(Delta Ex4/5) ) had a near-complete loss of ribbons from the synapses (up to 88% ribbonless synapses), gene-trap mutants (Bsn(gt)) showed weak residual expression of bassoon and 56% ribbonless synapses, whereas the remaining 44% had a loosely anchored ribbon. Patch-clamp recordings and synaptic Ca(V)1.3 immunolabeling indicated a larger number of Ca2+ channels for Bsngt IHCs compared with Bsn(Delta Ex4/5) IHCs and for Bsn(gt) ribbon-occupied versus Bsn(gt) ribbonless synapses. An intermediate phenotype of Bsngt IHCs was also found by membrane capacitance measurements for sustained exocytosis, but not for the size of the readily releasable vesicle pool. The frequency and amplitude of EPSCs were reduced in Bsn(Delta Ex4/5) mouse SGNs, whereas their postsynaptic AMPA receptor clusters were largely unaltered. Sound coding in SGN, assessed by recordings of single auditory nerve fibers and their population responses in vivo, was similarly affected in Bsn(gt) and Bsn(Delta Ex4/5) mice. Both genotypes showed impaired sound onset coding and reduced evoked and spontaneous spike rates. In summary, reduced bassoon expression or complete lack of full-length bassoon impaired sound encoding to a similar extent, which is consistent with the comparable reduction of the readily releasable vesicle pool. This suggests that the remaining loosely anchored ribbons in Bsngt IHCs were functionally inadequate or that ribbon independent mechanisms dominated the coding deficit."],["dc.identifier.doi","10.1523/JNEUROSCI.3491-12.2013"],["dc.identifier.gro","3142375"],["dc.identifier.isi","000315926300023"],["dc.identifier.pmid","23467361"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7586"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Disruption of the Presynaptic Cytomatrix Protein Bassoon Degrades Ribbon Anchorage, Multiquantal Release, and Sound Encoding at the Hair Cell Afferent Synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["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"]]

[["dc.bibliographiccitation.firstpage","10661"],["dc.bibliographiccitation.issue","26"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","10666"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:47:40Z"],["dc.date.available","2017-09-07T11:47:40Z"],["dc.date.issued","2013"],["dc.description.abstract","Hearing over a wide range of sound intensities is thought to require complementary coding by functionally diverse spiral ganglion neurons (SGNs), each changing activity only over a subrange. The foundations of SGN diversity are not well understood but likely include differences among their inputs: the presynaptic active zones (AZs) of inner hair cells (IHCs). Here we studied one candidate mechanism for causing SGN diversity-heterogeneity of Ca2+ influx among the AZs of IHCs-during postnatal development of the mouse cochlea. Ca2+ imaging revealed a change from regenerative to graded synaptic Ca2+ signaling after the onset of hearing, when in vivo SGN spike timing changed from patterned to Poissonian. Furthermore, we detected the concurrent emergence of stronger synaptic Ca2+ signals in IHCs and higher spontaneous spike rates in SGNs. The strengthening of Ca2+ signaling at a subset of AZs primarily reflected a gain of Ca2+ channels. We hypothesize that the number of Ca2+ channels at each IHC AZ critically determines the firing properties of its corresponding SGN and propose that AZ heterogeneity enables IHCs to decompose auditory information into functionally diverse SGNs."],["dc.identifier.doi","10.1523/JNEUROSCI.1215-13.2013"],["dc.identifier.gro","3142338"],["dc.identifier.isi","000320928900011"],["dc.identifier.pmid","23804089"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7175"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Concurrent Maturation of Inner Hair Cell Synaptic Ca2+ Influx and Auditory Nerve Spontaneous Activity around Hearing Onset in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","869"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","U116"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Lasarow, Livia"],["dc.contributor.author","Reuter, Kirsten"],["dc.contributor.author","Takago, Hideki"],["dc.contributor.author","Schwander, Martin"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Tarantino, Lisa M."],["dc.contributor.author","Bailey, Janice S."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Mueller, Ulrich"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:45:58Z"],["dc.date.available","2017-09-07T11:45:58Z"],["dc.date.issued","2010"],["dc.description.abstract","Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an aspartate to glycine substitution in the C2F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca2+ signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones replenished vesicles at lower rates than wild-type ones and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer interstimulus intervals. We conclude that replenishment does not match the release of vesicles at mutant active zones in vivo and a sufficient standing RRP therefore cannot be maintained. We propose that otoferlin is involved in replenishing synaptic vesicles."],["dc.identifier.doi","10.1038/nn.2578"],["dc.identifier.gro","3142900"],["dc.identifier.isi","000279173900020"],["dc.identifier.pmid","20562868"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/355"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1097-6256"],["dc.title","Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["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"]]

[["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"]]