Nouvian, Régis

[["dc.bibliographiccitation.firstpage","411"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","413"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Nouvian, Régis"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Bulankina, Anna V"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Sikorra, Stefan"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Binz, Thomas"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:44:19Z"],["dc.date.available","2017-09-07T11:44:19Z"],["dc.date.issued","2011"],["dc.description.abstract","SNARE proteins mediate membrane fusion. Neurosecretion depends on neuronal soluble NSF attachment protein receptors ( SNAREs; SNAP-25, syntaxin-1, and synaptobrevin-1 or synaptobrevin-2) and is blocked by neurotoxin-mediated cleavage or genetic ablation. We found that exocytosis in mouse inner hair cells (IHCs) was insensitive to neurotoxins and genetic ablation of neuronal SNAREs. mRNA, but no synaptically localized protein, of neuronal SNAREs was present in IHCs. Thus, IHC exocytosis is unconventional and may operate independently of neuronal SNAREs."],["dc.identifier.doi","10.1038/nn.2774"],["dc.identifier.gro","3142757"],["dc.identifier.isi","000288849400007"],["dc.identifier.pmid","21378973"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/196"],["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","Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins"],["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","278"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","292"],["dc.bibliographiccitation.volume","83"],["dc.contributor.author","Ruel, Jerome"],["dc.contributor.author","Emery, Sarah"],["dc.contributor.author","Nouvian, Regis"],["dc.contributor.author","Bersot, Tiphaine"],["dc.contributor.author","Amilhon, Benedicte"],["dc.contributor.author","Van Rybroek, Jana M."],["dc.contributor.author","Rebillard, Guy"],["dc.contributor.author","Lenoir, Marc"],["dc.contributor.author","Eybalin, Michel"],["dc.contributor.author","Delprat, Benjamin"],["dc.contributor.author","Sivakumaran, Theru A."],["dc.contributor.author","Giros, Bruno"],["dc.contributor.author","El Mestikawy, Salah"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Smith, Richard J. H."],["dc.contributor.author","Lesperance, Marci M."],["dc.contributor.author","Puel, Jean-Luc"],["dc.date.accessioned","2017-09-07T11:48:15Z"],["dc.date.available","2017-09-07T11:48:15Z"],["dc.date.issued","2008"],["dc.description.abstract","Autosomal-dominant sensorineural hearing loss is genetically heterogeneous, with a phenotype closely resembling presbycusis, the most common sensory defect associated with aging in humans. We have identified SLC17A8, which encodes the vesicular glutamate transporter-3 (VGLUT3), as the gene responsible for DFNA25, an autosomal-dominant form of progressive, high-frequency nonsyndromic deafness. In two unrelated families, a heterozygous missense mutation, c.632C -> T (p.A211V), was found to segregate with DFNA25 deafness and was not present in 267 controls. Linkage-disequilibrium analysis suggested that the families have a distant common ancestor. The A211 residue is conserved in VGLUT3 across species and in all human VGLUT subtypes (VGLUT1-3), suggesting an important functional role. In the cochlea, VGLUT3 accumulates glutamate in the synaptic vesicles of the sensory inner hair cells (IHCs) before releasing it onto receptors of auditory-nerve terminals. Null mice with a targeted deletion of Slc17a8 exon 2 lacked auditory-nerve responses to acoustic stimuli, although auditory brainstem responses could be elicited by electrical stimuli, and robust otoacoustic emissions were recorded. Ca2+-triggered synaptic-vesicle turnover was normal in IHCs of Slc17a8 null mice when probed by membrane capacitance measurements at 2 weeks of age. Later, the number of afferent synapses, spiral ganglion neurons, and lateral efferent endings below sensory IHCs declined. Ribbon synapses remaining by 3 months of age had a normal ultrastructural appearance. We conclude that deafness in Slc17a8-deficient mice is due to a specific defect of vesicular glutamate uptake and release and that VGLUT3 is essential for auditory coding at the IHC synapse."],["dc.identifier.doi","10.1016/j.ajhg.2008.07.008"],["dc.identifier.gro","3143258"],["dc.identifier.isi","000258418200013"],["dc.identifier.pmid","18674745"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/752"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIDCD NIH HHS [K23 DC000161, K23 DC00161, R01 DC003544, R01-DC003544]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0002-9297"],["dc.title","Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","153"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","Journal of Membrane Biology"],["dc.bibliographiccitation.lastpage","165"],["dc.bibliographiccitation.volume","209"],["dc.contributor.author","Nouvian, Regis"],["dc.contributor.author","Beutner, D."],["dc.contributor.author","Parsons, T. D."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:53:28Z"],["dc.date.available","2017-09-07T11:53:28Z"],["dc.date.issued","2006"],["dc.description.abstract","Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse - the electron-dense synaptic ribbon or synaptic body - has been recognized for decades, dissection of the synapse's molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years."],["dc.identifier.doi","10.1007/s00232-005-0854-4"],["dc.identifier.gro","3143759"],["dc.identifier.isi","000238293000006"],["dc.identifier.pmid","16773499"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11219"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1308"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIDCD NIH HHS [R01 DC3783, R01 DC003783]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.issn","0022-2631"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure and function of the hair cell ribbon synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4886"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","4895"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Bresee, Chris"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Nair, Ramya"],["dc.contributor.author","Reuter, Kirsten"],["dc.contributor.author","Bulankina, Anna"],["dc.contributor.author","Nouvian, Régis"],["dc.contributor.author","Koch, Manuel"],["dc.contributor.author","Bückers, Johanna"],["dc.contributor.author","Kastrup, Lars"],["dc.contributor.author","Roux, Isabelle"],["dc.contributor.author","Petit, Christine"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Brigande, John V."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:44:21Z"],["dc.date.available","2017-09-07T11:44:21Z"],["dc.date.issued","2011"],["dc.description.abstract","Cochlear inner hair cells (IHCs) use Ca(2+)-dependent exocytosis of glutamate to signal sound information. Otoferlin (Otof), a C(2) domain protein essential for IHC exocytosis and hearing, may serve as a Ca(2+) sensor in vesicle fusion in IHCs that seem to lack the classical neuronal Ca(2+) sensors synaptotagmin 1 (Syt1) and Syt2. Support for the Ca(2+) sensor of fusion hypothesis for otoferlin function comes from biochemical experiments, but additional roles in late exocytosis upstream of fusion have been indicated by physiological studies. Here, we tested the functional equivalence of otoferlin and Syt1 in three neurosecretory model systems: auditory IHCs, adrenal chromaffin cells, and hippocampal neurons. Long- term and short- term ectopic expression of Syt1 in IHCs of Otof(-/-) mice by viral gene transfer in the embryonic inner ear and organotypic culture failed to rescue their Ca(2+) influx- triggered exocytosis. Conversely, virally mediated overexpression of otoferlin did not restore phasic exocytosis in Syt1- deficient chromaffin cells or neurons but enhanced asynchronous release in the latter. We further tested exocytosis in Otof(-/-) hippocampal neurons and in Syt1(-/-) IHCs but found no deficits in vesicle fusion. Expression analysis of different synaptotagminisoforms indicated that Syt1andSyt2 are absentfrommatureIHCs. Ourdata argue againstasimple functional equivalence of the two C(2) domain proteins in exocytosis of IHC ribbon synapses, chromaffin cells, and hippocampal synapses."],["dc.identifier.doi","10.1523/JNEUROSCI.5122-10.2011"],["dc.identifier.gro","3142759"],["dc.identifier.isi","000288938200015"],["dc.identifier.pmid","21451027"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/198"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIDCD NIH HHS [P30 DC005983, R01 DC008595, R01DC8595]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0270-6474"],["dc.title","Probing the Functional Equivalence of Otoferlin and Synaptotagmin 1 in Exocytosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","705"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","716"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Reuter, Kirsten"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Lenz, Christine"],["dc.contributor.author","Nouvian, Regis"],["dc.contributor.author","Boumil, Rebecca M."],["dc.contributor.author","Frankel, Wayne N."],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:46:53Z"],["dc.date.available","2017-09-07T11:46:53Z"],["dc.date.issued","2014"],["dc.description.abstract","Synaptic vesicle recycling sustains high rates of neurotransmission at the ribbon-type active zones (AZs) of mouse auditory inner hair cells (IHCs), but its modes and molecular regulation are poorly understood. Electron microscopy indicated the presence of clathrin-mediated endocytosis (CME) and bulk endocytosis. The endocytic proteins dynamin, clathrin, and amphiphysin are expressed and broadly distributed in IHCs. We used confocal vglut1-pHluorin imaging and membrane capacitance (C-m) measurements to study the spatial organization and dynamics of IHC exocytosis and endocytosis. Viral gene transfer expressed vglut1-pHluorin in IHCs and targeted it to synaptic vesicles. The intravesicular pH was similar to 6.5, supporting only a modest increase of vglut1-pHluorin fluorescence during exocytosis and pH neutralization. Ca2+ influx triggered an exocytic increase of vglut1-pHluorin fluorescence at the AZs, around which it remained for several seconds. The endocytic C-m decline proceeded with constant rate (linear component) after exocytosis of the readily releasable pool (RRP). When exocytosis exceeded three to four RRP equivalents, IHCs additionally recruited a faster C-m decline (exponential component) that increased with the amount of preceding exocytosis and likely reflects bulk endocytosis. The dynamin inhibitor Dyngo-4a and the clathrin blocker pitstop 2 selectively impaired the linear component of endocytic C-m decline. A missense mutation of dynamin 1 (fitful) inhibited endocytosis to a similar extent as Dyngo-4a. We propose that IHCs use dynamin-dependent endocytosis via CME to support vesicle cycling during mild stimulation but recruit bulk endocytosis to balance massive exocytosis."],["dc.identifier.doi","10.1523/JNEUROSCI.3313-13.2014"],["dc.identifier.gro","3142198"],["dc.identifier.isi","000329916600004"],["dc.identifier.pmid","24431429"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5621"],["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","Modes and Regulation of Endocytic Membrane Retrieval in Mouse Auditory 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","277"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","289"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Roux, Isabelle"],["dc.contributor.author","Safieddine, Saaid"],["dc.contributor.author","Nouvian, Regis"],["dc.contributor.author","Grati, M."],["dc.contributor.author","Simmler, Marie-Christine"],["dc.contributor.author","Bahloul, Isabelle"],["dc.contributor.author","Perfettini, Isabelle"],["dc.contributor.author","Le Gall, Morgane"],["dc.contributor.author","Rostaing, Philippe"],["dc.contributor.author","Hamard, Ghislaine"],["dc.contributor.author","Triller, Antoine"],["dc.contributor.author","Avan, Paul"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Petit, Christine"],["dc.date.accessioned","2017-09-07T11:52:30Z"],["dc.date.available","2017-09-07T11:52:30Z"],["dc.date.issued","2006"],["dc.description.abstract","The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synapto-genesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca2+ and displays Ca2+,-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca2+ current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca2+ sensor triggering membrane fusion at the IHC ribbon synapse."],["dc.identifier.doi","10.1016/j.cell.2006.08.040"],["dc.identifier.gro","3143609"],["dc.identifier.isi","000241827100016"],["dc.identifier.pmid","17055430"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1142"],["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","0092-8674"],["dc.title","Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory 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","535"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","542"],["dc.bibliographiccitation.volume","584"],["dc.contributor.author","Nouvian, Regis"],["dc.date.accessioned","2018-11-07T10:57:47Z"],["dc.date.available","2018-11-07T10:57:47Z"],["dc.date.issued","2007"],["dc.description.abstract","Hearing relies on fast and sustained neurotransmitter release from inner hair cells (IHCs) onto the afferent auditory nerve fibres. The temperature dependence of Ca2+ current and transmitter release at the IHCs ribbon synapse has not been investigated thus far. To assess the influence of temperature on calcium-triggered exocytosis, patch-clamp recordings of voltage-gated L-type Ca2+ influx and exocytic membrane capacitance changes were performed at room (25 degrees C) and physiological (35-37 degrees C) temperatures. An increase in temperature within this range increased the L-type Ca2+ current amplitude of IHCs (Q(10) = 1.3) and accelerates the activation kinetics. Fast exocytosis, probed by 20 ms depolarization, was enhanced at physiological temperature with a Q(10) of 2.1. The amplitude of fast release was elevated disproportionately to the increase in Ca2+ influx. In contrast, the rate of sustained exocytosis (exocytic rate between 20 and 100 ms of depolarization) did not show a significant increase at physiological temperature. Altogether, these data indicate that the efficiency of fast exocytosis is higher at physiological temperature than at room temperature and suggest that the number of readily releasable vesicles available at the active zone is higher at physiological temperature."],["dc.identifier.doi","10.1113/jphysiol.2007.139675"],["dc.identifier.isi","000250651300019"],["dc.identifier.pmid","17717016"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50332"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3751"],["dc.title","Temperature enhances exocytosis efficiency at the mouse inner hair cell ribbon synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","642"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","652"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Kharkovets, Tatjana"],["dc.contributor.author","Dedek, Karin"],["dc.contributor.author","Maier, Hannes"],["dc.contributor.author","Schweizer, Michaela"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Nouvian, Régis"],["dc.contributor.author","Vardanyan, Vitya"],["dc.contributor.author","Leuwer, Rudolf"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Jentsch, Thomas J."],["dc.date.accessioned","2017-09-07T11:53:24Z"],["dc.date.available","2017-09-07T11:53:24Z"],["dc.date.issued","2006"],["dc.description.abstract","KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2 dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is strongly expressed in vestibular hair cells, vestibular function appeared normal. Auditory function was only slightly impaired initially. It then declined over several weeks in Kcnq4(-/-) mice and over several months in mice carrying the dominant negative allele. This progressive hearing loss was paralleled by a selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the I-K,I- n current of OHCs. The ensuing depolarization of OHCs impaired sound amplification. Inner hair cells and their afferent synapses remained mostly intact. These cells were only slightly depolarized and showed near-normal presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly caused by a slow degeneration of OHCs resulting from chronic depolarization."],["dc.identifier.doi","10.1038/sj.emboj.7600951"],["dc.identifier.gro","3143740"],["dc.identifier.isi","000235803100019"],["dc.identifier.pmid","16437162"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1287"],["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","0261-4189"],["dc.title","Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2253"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","2267"],["dc.bibliographiccitation.volume","42"],["dc.contributor.author","Huet, Antoine"],["dc.contributor.author","Batrel, Charlène"],["dc.contributor.author","Dubernard, Xavier"],["dc.contributor.author","Kleiber, Jean-Charles"],["dc.contributor.author","Desmadryl, Gilles"],["dc.contributor.author","Venail, Frédéric"],["dc.contributor.author","Liberman, M. Charles"],["dc.contributor.author","Nouvian, Régis"],["dc.contributor.author","Puel, Jean-Luc"],["dc.contributor.author","Bourien, Jérôme"],["dc.date.accessioned","2022-05-02T08:09:30Z"],["dc.date.available","2022-05-02T08:09:30Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1523/JNEUROSCI.0858-21.2022"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107394"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation.eissn","1529-2401"],["dc.relation.issn","0270-6474"],["dc.title","Peristimulus Time Responses Predict Adaptation and Spontaneous Firing of Auditory-Nerve Fibers: From Rodents Data to Humans"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]