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","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.journal","The Journal of Physiological Sciences"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Pangsric, Tina"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Brandt, Andreas"],["dc.contributor.author","Meyer, Alexander C."],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Striessnig, Joerg"],["dc.contributor.author","Gregg, Ronald R."],["dc.contributor.author","Petit, Christine"],["dc.contributor.author","Schwaller, Beat"],["dc.contributor.author","Khimich, Darina"],["dc.date.accessioned","2018-11-07T08:34:55Z"],["dc.date.available","2018-11-07T08:34:55Z"],["dc.date.issued","2009"],["dc.format.extent","30"],["dc.identifier.isi","000271023100099"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17937"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Tokyo"],["dc.relation.issn","1880-6546"],["dc.title","Molecular Physiology Of The Hair Cell Ribbon Synapse"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]