Khimich, Darina

[["dc.bibliographiccitation.firstpage","444"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","453"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Meyer, Alexander C."],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Chapochnikov, Nikolai M."],["dc.contributor.author","Yarin, Yury M."],["dc.contributor.author","Harke, Benjamin"],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:47:30Z"],["dc.date.available","2017-09-07T11:47:30Z"],["dc.date.issued","2009"],["dc.description.abstract","Cochlear inner hair cells (IHCs) transmit acoustic information to spiral ganglion neurons through ribbon synapses. Here we have used morphological and physiological techniques to ask whether synaptic mechanisms differ along the tonotopic axis and within IHCs in the mouse cochlea. We show that the number of ribbon synapses per IHC peaks where the cochlea is most sensitive to sound. Exocytosis, measured as membrane capacitance changes, scaled with synapse number when comparing apical and midcochlear IHCs. Synapses were distributed in the subnuclear portion of IHCs. High-resolution imaging of IHC synapses provided insights into presynaptic Ca2+ channel clusters and Ca2+ signals, synaptic ribbons and postsynaptic glutamate receptor clusters and revealed subtle differences in their average properties along the tonotopic axis. However, we observed substantial variability for presynaptic Ca2+ signals, even within individual IHCs, providing a candidate presynaptic mechanism for the divergent dynamics of spiral ganglion neuron spiking."],["dc.identifier.doi","10.1038/nn.2293"],["dc.identifier.gro","3143132"],["dc.identifier.isi","000264563100019"],["dc.identifier.pmid","19270686"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/612"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1097-6256"],["dc.title","Tuning of synapse number, structure and function in the cochlea"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","889"],["dc.bibliographiccitation.issue","7035"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","894"],["dc.bibliographiccitation.volume","434"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Nouvian, Regis"],["dc.contributor.author","Pujol, R"],["dc.contributor.author","Dieck, Susanne Tom"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Gundelfinger, Eckart D."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:54:29Z"],["dc.date.available","2017-09-07T11:54:29Z"],["dc.date.issued","2005"],["dc.description.abstract","Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs)(1-3). At present, the function of presynaptic ribbons at these synapses is still largely unknown(1,4). Here we show that anchoring of IHC ribbons is impaired in mouse mutants for the presynaptic scaffolding protein Bassoon. The lack of active-zone-anchored synaptic ribbons reduced the presynaptic readily releasable vesicle pool, and impaired synchronous auditory signalling as revealed by recordings of exocytic IHC capacitance changes and sound-evoked activation of spiral ganglion neurons. Both exocytosis of the hair cell releasable vesicle pool and the number of synchronously activated spiral ganglion neurons co-varied with the number of anchored ribbons during development. Interestingly, ribbon-deficient IHCs were still capable of sustained exocytosis with normal Ca2+-dependence. Endocytic membrane retrieval was intact, but an accumulation of tubular and cisternal membrane profiles was observed in ribbon-deficient IHCs. We conclude that ribbon-dependent synchronous release of multiple vesicles at the hair cell afferent synapse is essential for normal hearing."],["dc.identifier.doi","10.1038/nature03418"],["dc.identifier.gro","3143866"],["dc.identifier.isi","000228327600039"],["dc.identifier.pmid","15829963"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1427"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0028-0836"],["dc.title","Hair cell synaptic ribbons are essential for synchronous auditory signalling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","707"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","HNO"],["dc.bibliographiccitation.lastpage","714"],["dc.bibliographiccitation.volume","60"],["dc.contributor.author","Meyer, Alexander C."],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-11-07T09:07:36Z"],["dc.date.available","2018-11-07T09:07:36Z"],["dc.date.issued","2012"],["dc.description.abstract","Inner hair cells encode sound into action potentials in the auditory nerve. Spiral ganglion neurons form the afferent innervation of inner hair cells via the hair cell synapse. The structure and function of this ribbon-type synapse is considered to have a major impact on the sound encoding process itself. In this study we have used conventional confocal microscopy as well as super-resolution techniques to investigate the synaptic organization in the inner hair cells of mice. Functionally relevant proteins of the afferent inner hair cell synapse were selectively marked using immunohistochemical methods and investigated with conventional confocal and super-resolution 4Pi- and stimulated emission depletion (STED) techniques. Synapse and innervation density was mapped over the entire tonotopic axis. We found inner hair cells in the region of best hearing to have about twice the number of afferent fibres compared to the apex or base of the cochlea. For the first time 4Pi and STED microscopic techniques were employed to resolve the fine structure of these synapses beyond the resolution of conventional light microscopy. With 4Pi a resolution of approximately 100 nm in the z-axis direction is feasible. In practice STED delivers an effective resolution between 150 and 30 nm, depending on the power of the lasers employed. Synapses at different tonotopic positions of the cochlea exhibit no relevant structural differences at this level of resolution. The 4Pi and STED microscopic techniques are capable of showing the structure of afferent synapses in the organ of Corti with unsurpassed resolution. These images contribute to our understanding of sound-encoding mechanisms in the inner ear."],["dc.identifier.doi","10.1007/s00106-011-2457-y"],["dc.identifier.isi","000307294000004"],["dc.identifier.pmid","22767188"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25836"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0017-6192"],["dc.title","Super-resolution optical microscopy of the organ of Corti. Investigations on the fine structure of the inner hair cell afferent synapse by the 4Pi and STED techniques"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","12933"],["dc.bibliographiccitation.issue","47"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","12944"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Pirih, Primoz"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:49:23Z"],["dc.date.available","2017-09-07T11:49:23Z"],["dc.date.issued","2007"],["dc.description.abstract","Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs). Postsynaptic recordings from this synapse in prehearing animals had delivered strong indications for synchronized release of several vesicles. The underlying mechanism, however, remains unclear. Here, we used presynaptic membrane capacitance measurements to test whether IHCs release vesicles in a statistically independent or dependent ( coordinated) manner. Exocytic changes of membrane capacitance (Delta C-m) were repeatedly stimulated in IHCs of prehearing and hearing mice by short depolarizations to preferentially recruit the readily releasable pool of synaptic vesicles. A compound Poisson model was devised to describe hair cell exocytosis and to test the analysis. From the trial-to-trial fluctuations of the Delta C-m we were able to estimate the apparent size of the elementary fusion event (C-app) at the hair cell synapse to be 96-223 aF in immature and 55-149 aF in mature IHCs. We also approximated the single vesicle capacitance in IHCs by measurements of synaptic vesicle diameters in electron micrographs. The results (immature, 48 aF; mature, 45 aF) were lower than the respective Capp estimates. This indicates that coordinated exocytosis of synaptic vesicles occurs at both immature and mature hair cell synapses. Approximately 35% of the release events in mature IHCs and similar to 50% in immature IHCs were predicted to involve coordinated fusion, when assuming a geometric distribution of elementary sizes. In summary, our presynaptic measurements indicate coordinated exocytosis but argue for a lesser degree of coordination than suggested by postsynaptic recordings."],["dc.identifier.doi","10.1523/JNEUROSCI.1996-07.2007"],["dc.identifier.gro","3143408"],["dc.identifier.isi","000251157200022"],["dc.identifier.pmid","18032667"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/919"],["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","Probing the mechanism of exocytosis at the hair cell ribbon synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2926"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","2931"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Schmitz, F."],["dc.contributor.author","Tabares, Lucia"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Villa-Polo, P. de la"],["dc.contributor.author","Castellano-Munoz, M."],["dc.contributor.author","Bulankina, Anna V."],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Fernandez-Chacon, R"],["dc.contributor.author","Suedhof, Thomas C."],["dc.date.accessioned","2017-09-07T11:53:17Z"],["dc.date.available","2017-09-07T11:53:17Z"],["dc.date.issued","2006"],["dc.description.abstract","Cysteine string protein (CSP) alpha is an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40-type cochaperones. Previous studies showed that deletion of CSP alpha in mice leads to massive lethal neurodegeneration but did not clarify how the neurodegeneration affects specific subpopulations of neurons. Here, we analyzed the effects of the CSP alpha deficiency on tonically active ribbon synapses of the retina and the inner ear. We show that CSP alpha-deficient photoreceptor terminals undergo dramatic and rapidly progressive neurodegeneration that starts before eye opening and initially does not affect other retinal synapses. These changes are associated with progressive blindness. In contrast, ribbon synapses of auditory hair cells did not exhibit presynaptic impairments in CSP alpha-deficient mice. Hair cells, but not photoreceptor cells or central neurons, express CSP beta, thereby accounting for the lack of a hair-cell phenotype in CSP alpha knockout mice. Our data demonstrate that tonically active ribbon synapses in retina are particularly sensitive to the deletion of CSP alpha and that expression of at least one CSP isoform is essential to protect such tonically active synapses from neurodegeneration."],["dc.identifier.doi","10.1073/pnas.0510060103"],["dc.identifier.gro","3143736"],["dc.identifier.isi","000235554900080"],["dc.identifier.pmid","16477021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1283"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","CSP alpha-deficiency causes massive and rapid photoreceptor degeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11577"],["dc.bibliographiccitation.issue","50"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","11585"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Brandt, Andreas"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:53:40Z"],["dc.date.available","2017-09-07T11:53:40Z"],["dc.date.issued","2005"],["dc.description.abstract","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."],["dc.identifier.doi","10.1523/JNEUROSCI.3411-05.2005"],["dc.identifier.gro","3143772"],["dc.identifier.isi","000233942200011"],["dc.identifier.pmid","16354915"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1322"],["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","Few Ca(V)1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["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"]]

[["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","1849"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","1860"],["dc.bibliographiccitation.volume","141"],["dc.contributor.author","Nemzou, R. M."],["dc.contributor.author","Bulankina, A. V."],["dc.contributor.author","Khimich, D."],["dc.contributor.author","Giese, A."],["dc.contributor.author","Moser, T."],["dc.date.accessioned","2017-09-07T11:53:36Z"],["dc.date.available","2017-09-07T11:53:36Z"],["dc.date.issued","2006"],["dc.description.abstract","Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. Normal development and function of inner hair cells require the expression of a subunit 1.3 forming L-type voltage-gated Ca(2+) channel (Ca(v)1.3). Here, we used immunohistochemistry and reverse transcri ption-polymerase chain reaction to study the synaptic organization and expression of large conductance Ca(2+)-activated potassium channels in IHCs of mice lacking the Ca(v)1.3 Ca(2+) channel (Ca(v)1.3(-/-)). Despite the near complete block of evoked afferent synaptic transmission, hair cell ribbon synapses were formed and remained preserved for at least 4 weeks after birth. Moreover, these \"silent\" afferent synapses held major components of the synaptic machinery such as Bassoon, Piccolo, and CSP. Hence, the block of exocytosis might be solely attributed to the lack of Ca(2+) influx through Ca(v)1.3 channels. Later on, Ca(v)1.3 deficient IHCs subsequently lost their afferent synapses. This was probably due to a secondary degeneration of the postsynaptic spiral ganglion neurons. In line with a prolonged efferent synaptic transmission onto Ca(v)1.3 deficient IHCs, which normally ceases around onset of hearing, we found juxtaposed immunoreactive spots of efferent presynaptic synaptophysin and postsynaptic (IHCs) small conductance Ca(2+)-activated potassium channels (SK channels) up to six weeks after birth. Finally, we show a substantial reduction of mRNA for the a subunit of the large conductance Ca(2+)-activated potassium channel (BK) in the apical cochlea, suggesting a reduced transcription of its gene in Ca(v)1.3 deficient IHCs. Ca(v)1.3 deficient IHCs lacked the apical spot-like immunoreactivity of clustered BK channels, which normally contribute to the temporal precision of hair cell afferent synaptic transmission. In summary, these data indicate that the Ca(v)1.3 channels are crucially involved in regulation of the expression of BK and SK channels. Ca(v)1.3 channels seem not to be essential for ribbon synapse formation, but are required for the maintenance of ribbon synapses and spiral ganglion neurons. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neuroscience.2006.05.057"],["dc.identifier.gro","3143764"],["dc.identifier.isi","000240222000019"],["dc.identifier.pmid","16828974"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1314"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0306-4522"],["dc.title","Synaptic organization in cochlear inner hair cells deficient for the Ca(V)1.3 (alpha 1D) subunit of L-type Ca(2+) channels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]