Ohn, Tzu-Lun

[["dc.bibliographiccitation.artnumber","290"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Urban, Nicolai T."],["dc.contributor.author","Ohn, Tzu-Lun"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Jean, Philippe"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Willig, Katrin I."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-04-23T11:48:23Z"],["dc.date.available","2018-04-23T11:48:23Z"],["dc.date.issued","2018"],["dc.description.abstract","Ca2+ influx triggers the release of synaptic vesicles at the presynaptic active zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is critical for understanding synaptic transmission. However, this has remained challenging to establish at the required resolution. Here, we employ confocal and stimulated emission depletion (STED) microscopy to quantify the number (20–330) and arrangement (mostly linear 70 nm × 100–600 nm clusters) of Ca2+ channels at AZs of mouse cochlear inner hair cells (IHCs). Establishing STED Ca2+ imaging, we analyze presynaptic Ca2+ signals at the nanometer scale and find confined elongated Ca2+ domains at normal IHC AZs, whereas Ca2+ domains are spatially spread out at the AZs of bassoon-deficient IHCs. Performing 2D-STED fluorescence lifetime analysis, we arrive at estimates of the Ca2+ concentrations at stimulated IHC AZs of on average 25 µM. We propose that IHCs form bassoon-dependent presynaptic Ca2+-channel clusters of similar density but scalable length, thereby varying the number of Ca2+ channels amongst individual AZs."],["dc.identifier.doi","10.1038/s41467-017-02612-y"],["dc.identifier.gro","3142361"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15588"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13498"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Quantitative optical nanophysiology of Ca2+ signaling at inner hair cell active zones"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E4716"],["dc.bibliographiccitation.issue","32"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E4725"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Ohn, Tzu-Lun"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Scharinger, Anja"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:53:13Z"],["dc.date.available","2017-09-07T11:53:13Z"],["dc.date.issued","2016"],["dc.description.abstract","For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca2+ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over ∼20 mV. Ca2+ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca2+ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca2+ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca2+ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca2+ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs."],["dc.identifier.doi","10.1073/pnas.1605737113"],["dc.identifier.gro","3145053"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2747"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0027-8424"],["dc.title","Hair cells use active zones with different voltage dependence of Ca2+influx to decompose sounds into complementary neural codes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]