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","247"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","264"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Gabrielaitis, Mantas"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Michanski, Susann"],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:46:33Z"],["dc.date.available","2017-09-07T11:46:33Z"],["dc.date.issued","2014"],["dc.description.abstract","Cochlear inner hair cells (IHCs) develop from pre-sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) Ca(V)1.3 channels formed stripe-like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic Ca(V)1.3-channels were selectively reduced, (iv) the intrinsic Ca2+ dependence of fast exocytosis probed by Ca2+ uncaging remained unchanged but (v) the apparent Ca2+ dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca2+ influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca2+ influx through an individual channel dominates the [Ca2+] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca2+ influx and exocytosis."],["dc.identifier.doi","10.1002/embj.201387110"],["dc.identifier.gro","3142187"],["dc.identifier.isi","000331394400008"],["dc.identifier.pmid","24442635"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5499"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis"],["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","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"]]