Strenzke, Nicola

[["dc.bibliographiccitation.artnumber","e2005114"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Cruces-Solís, Hugo"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Babaev, Olga"],["dc.contributor.author","Rubin, Jonathan"],["dc.contributor.author","Gür, Burak"],["dc.contributor.author","Krueger-Burg, Dilja"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","de Hoz, Livia"],["dc.date.accessioned","2020-11-24T10:40:59Z"],["dc.date.available","2020-11-24T10:40:59Z"],["dc.date.issued","2018"],["dc.description.abstract","Detecting regular patterns in the environment, a process known as statistical learning, is essential for survival. Neuronal adaptation is a key mechanism in the detection of patterns that are continuously repeated across short (seconds to minutes) temporal windows. Here, we found in mice that a subcortical structure in the auditory midbrain was sensitive to patterns that were repeated discontinuously, in a temporally sparse manner, across windows of minutes to hours. Using a combination of behavioral, electrophysiological, and molecular approaches, we found changes in neuronal response gain that varied in mechanism with the degree of sound predictability and resulted in changes in frequency coding. Analysis of population activity (structural tuning) revealed an increase in frequency classification accuracy in the context of increased overlap in responses across frequencies. The increase in accuracy and overlap was paralleled at the behavioral level in an increase in generalization in the absence of diminished discrimination. Gain modulation was accompanied by changes in gene and protein expression, indicative of long-term plasticity. Physiological changes were largely independent of corticofugal feedback, and no changes were seen in upstream cochlear nucleus responses, suggesting a key role of the auditory midbrain in sensory gating. Subsequent behavior demonstrated learning of predictable and random patterns and their importance in auditory conditioning. Using longer timescales than previously explored, the combined data show that the auditory midbrain codes statistical learning of temporally sparse patterns, a process that is critical for the detection of relevant stimuli in the constant soundscape that the animal navigates through."],["dc.identifier.doi","10.1371/journal.pbio.2005114"],["dc.identifier.pmid","30048446"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15664"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69155"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Auditory midbrain coding of statistical learning that results from discontinuous sensory stimulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e52069"],["dc.bibliographiccitation.issue","92"],["dc.bibliographiccitation.journal","Journal of Visualized Experiments"],["dc.contributor.author","Hernandez, Victor H."],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:45:27Z"],["dc.date.available","2017-09-07T11:45:27Z"],["dc.date.issued","2014"],["dc.description.abstract","Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects(1-6). Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea(7-9). Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of the cochlea has been used to evoke responses in the auditory nerve(10). Nevertheless it requires higher energies than electrical stimulation(10,11) and uncertainty remains as to the underlying mechanism(12). Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)(13) or virus-mediated expression of the ChR2-variant CatCh(14). We used micro-light emitting diodes (mu LEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation."],["dc.identifier.doi","10.3791/52069"],["dc.identifier.gro","3142038"],["dc.identifier.isi","000349303100063"],["dc.identifier.pmid","25350571"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3856"],["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","1940-087X"],["dc.title","Optogenetic Stimulation of the Auditory Nerve. Towards an Optical Cochlear Prosthetic"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2686"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","2702"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Maritzen, Tanja"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Revelo, Natalia H."],["dc.contributor.author","Al-Moyed, Hanan"],["dc.contributor.author","Meese, Sandra"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Panou, Iliana"],["dc.contributor.author","Bulut, Haydar"],["dc.contributor.author","Schu, Peter"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Rizzoli, Silvio"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Haucke, Volker"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:54:53Z"],["dc.date.available","2017-09-07T11:54:53Z"],["dc.date.issued","2015"],["dc.description.abstract","Active zones (AZs) of inner hair cells (IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. Here, we report that the endocytic adaptor protein 2 (AP-2) is required for release site replenishment and hearing. We show that hair cell-specific disruption of AP-2 slows IHC exocytosis immediately after fusion of the readily releasable pool of vesicles, despite normal abundance of membrane-proximal vesicles and intact endocytic membrane retrieval. Sound-driven postsynaptic spiking was reduced in a use-dependent manner, and the altered interspike interval statistics suggested a slowed reloading of release sites. Sustained strong stimulation led to accumulation of endosome-like vacuoles, fewer clathrin-coated endocytic intermediates, andvesicle depletion of the membrane-distal synaptic ribbon in AP-2-deficient IHCs, indicating a further role of AP-2 in clathrin-dependent vesicle reformation on a timescale of many seconds. Finally, we show that AP-2 sorts its IHC-cargo otoferlin. We propose that binding of AP-2 to otoferlin facilitates replenishment of release sites, for example, via speeding AZ clearance of exocytosed material, in addition to a role of AP-2 in synaptic vesicle reformation."],["dc.identifier.doi","10.15252/embj.201591885"],["dc.identifier.gro","3141791"],["dc.identifier.isi","000364337100008"],["dc.identifier.pmid","26446278"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1112"],["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","Disruption of adaptor protein 2μ (AP‐2μ) in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing"],["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","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"]]

[["dc.bibliographiccitation.firstpage","1114"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","1129"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Hernandez, Victor H."],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Reuter, Kirsten"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Schulz, Alejandro Mendoza"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Bartels, Matthias"],["dc.contributor.author","Vogt, Gerhard"],["dc.contributor.author","Garnham, Carolyn W."],["dc.contributor.author","Yawo, Hiromu"],["dc.contributor.author","Fukazawa, Yugo"],["dc.contributor.author","Augustine, George J."],["dc.contributor.author","Bamberg, Ernst"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Salditt, Tim"],["dc.contributor.author","Hoz, Livia de"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:46:28Z"],["dc.date.available","2017-09-07T11:46:28Z"],["dc.date.issued","2014"],["dc.description.abstract","Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics."],["dc.identifier.doi","10.1172/JCI69050"],["dc.identifier.gro","3142178"],["dc.identifier.isi","000332347700030"],["dc.identifier.pmid","24509078"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5399"],["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","1558-8238"],["dc.relation.issn","0021-9738"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Optogenetic stimulation of the auditory pathway"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["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","512"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","527"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Schulz, Alejandro Mendoza"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Caro, Juan Maria Sanchez"],["dc.contributor.author","Wetzel, Friederike"],["dc.contributor.author","Dresbach, Thomas"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:46:28Z"],["dc.date.available","2017-09-07T11:46:28Z"],["dc.date.issued","2014"],["dc.description.abstract","Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse."],["dc.identifier.doi","10.1002/embj.201385887"],["dc.identifier.gro","3142175"],["dc.identifier.isi","000332391600012"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5366"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E3141"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E3149"],["dc.bibliographiccitation.volume","112"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Oshima-Takago, Tomoko"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Yamanbaeva, Gulnara"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Michel, Katrin"],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Schoch, Susanne"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:43:46Z"],["dc.date.available","2017-09-07T11:43:46Z"],["dc.date.issued","2015"],["dc.description.abstract","Ca2+ influx triggers the fusion of synaptic vesicles at the presynaptic active zone (AZ). Here we demonstrate a role of Ras-related in brain 3 (Rab3)-interacting molecules 2 alpha and beta (RIM2 alpha and RIM2 beta) in clustering voltage-gated Ca(V)1.3 Ca2+ channels at the AZs of sensory inner hair cells (IHCs). We show that IHCs of hearing mice express mainly RIM2 alpha, but also RIM2 beta and RIM3., which all localize to the AZs, as shown by immunofluorescence microscopy. Immunohistochemistry, patch-clamp, fluctuation analysis, and confocal Ca2+ imaging demonstrate that AZs of RIM2 alpha-deficient IHCs cluster fewer synaptic Ca(V)1.3 Ca2+ channels, resulting in reduced synaptic Ca2+ influx. Using superresolution microscopy, we found that Ca2+ channels remained clustered in stripes underneath anchored ribbons. Electron tomography of high-pressure frozen synapses revealed a reduced fraction of membrane-tethered vesicles, whereas the total number of membrane-proximal vesicles was unaltered. Membrane capacitance measurements revealed a reduction of exocytosis largely in proportion with the Ca2+ current, whereas the apparent Ca2+ dependence of exocytosis was unchanged. Hair cell-specific deletion of all RIM2 isoforms caused a stronger reduction of Ca2+ influx and exocytosis and significantly impaired the encoding of sound onset in the postsynaptic spiral ganglion neurons. Auditory brainstem responses indicated a mild hearing impairment on hair cell-specific deletion of all RIM2 isoforms or global inactivation of RIM2 alpha. We conclude that RIM2 alpha and RIM2 beta promote a large complement of synaptic Ca2+ channels at IHC AZs and are required for normal hearing."],["dc.identifier.doi","10.1073/pnas.1417207112"],["dc.identifier.gro","3141887"],["dc.identifier.isi","000356251800010"],["dc.identifier.pmid","26034270"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2178"],["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","0027-8424"],["dc.title","Rab3-interacting molecules 2α and 2β promote the abundance of voltage-gated CaV1.3 Ca2+ channels at hair cell active zones"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]