Reisinger, Ellen

[["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.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","15"],["dc.contributor.affiliation","Stalmann, Ursula; 1Auditory Systems Physiology Group, Department of Otolaryngology and Institute for Auditory Neuroscience, SFB 889 project A06, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Franke, Albert Justin; 1Auditory Systems Physiology Group, Department of Otolaryngology and Institute for Auditory Neuroscience, SFB 889 project A06, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Al-Moyed, Hanan; 2Molecular Biology of Cochlear Neurotransmission Group, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Strenzke, Nicola; 1Auditory Systems Physiology Group, Department of Otolaryngology and Institute for Auditory Neuroscience, SFB 889 project A06, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Reisinger, Ellen; 2Molecular Biology of Cochlear Neurotransmission Group, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Stalmann, Ursula"],["dc.contributor.author","Franke, Albert Justin"],["dc.contributor.author","Al-Moyed, Hanan"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Reisinger, Ellen"],["dc.date.accessioned","2021-09-01T06:38:17Z"],["dc.date.available","2021-09-01T06:38:17Z"],["dc.date.issued","2021"],["dc.date.updated","2022-02-09T13:20:49Z"],["dc.description.abstract","Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out ( Otof –/– ) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof –/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof –/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof –/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof –/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients."],["dc.description.abstract","Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out ( Otof –/– ) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof –/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof –/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof –/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof –/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients."],["dc.identifier.doi","10.3389/fncel.2021.677543"],["dc.identifier.eissn","1662-5102"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88902"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5102"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","40"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Westekemper, Katharina"],["dc.contributor.author","Ehrenreich, Ludwig"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Fischer, Julia"],["dc.date.accessioned","2017-09-07T11:47:41Z"],["dc.date.available","2017-09-07T11:47:41Z"],["dc.date.issued","2012"],["dc.description.abstract","BACKGROUND:Transgenic mice have become an important tool to elucidate the genetic foundation of the human language faculty. While learning is an essential prerequisite for the acquisition of human speech, it is still a matter of debate whether auditory learning plays any role in the development of species-specific vocalizations in mice. To study the influence of auditory input on call development, we compared the occurrence and structure of ultrasonic vocalizations from deaf otoferlin-knockout mice, a model for human deafness DFNB9, to those of hearing wild-type and heterozygous littermates.RESULTS:We found that the occurrence and structure of ultrasonic vocalizations recorded from deaf otoferlin-knockout mice and hearing wild-type and heterozygous littermates do not differ. Isolation calls from 16 deaf and 15 hearing pups show the same ontogenetic development in terms of the usage and structure of their vocalizations as their hearing conspecifics. Similarly, adult courtship 'songs' produced by 12 deaf and 16 hearing males did not differ in the latency to call, rhythm of calling or acoustic structure.CONCLUSION:The results indicate that auditory experience is not a prerequisite for the development of species-specific vocalizations in mice. Thus, mouse models are of only limited suitability to study the evolution of vocal learning, a crucial component in the development of human speech. Nevertheless, ultrasonic vocalizations of mice constitute a valuable readout in studies of the genetic foundations of social and communicative behavior."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1186/1471-2202-13-40"],["dc.identifier.gro","3150690"],["dc.identifier.pmid","22533376"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7598"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7474"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","1471-2202"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.subject","DFNB9; Evolution; Language; Mice; Ontogeny; Otoferlin; Speech; Vocal learning"],["dc.title","Mice do not require auditory input for the normal development of their ultrasonic vocalizations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2519"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","2535"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Al‐Moyed, Hanan"],["dc.contributor.author","Müller, Alexandra"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Pangrsic, Tina"],["dc.contributor.author","Yamanbaeva, Gulnara"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Pan, Kuan‐Ting"],["dc.contributor.author","Auge, Elisabeth"],["dc.contributor.author","Geiss‐Friedlander, Ruth"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Reisinger, Ellen"],["dc.date.accessioned","2017-09-07T11:52:19Z"],["dc.date.available","2017-09-07T11:52:19Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.15252/embj.201694564"],["dc.identifier.gro","3144895"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2570"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0261-4189"],["dc.title","Hair cell synaptic dysfunction, auditory fatigue and thermal sensitivity in otoferlin Ile515Thr mutants"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","869"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","U116"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Lasarow, Livia"],["dc.contributor.author","Reuter, Kirsten"],["dc.contributor.author","Takago, Hideki"],["dc.contributor.author","Schwander, Martin"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Tarantino, Lisa M."],["dc.contributor.author","Bailey, Janice S."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Mueller, Ulrich"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:45:58Z"],["dc.date.available","2017-09-07T11:45:58Z"],["dc.date.issued","2010"],["dc.description.abstract","Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an aspartate to glycine substitution in the C2F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca2+ signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones replenished vesicles at lower rates than wild-type ones and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer interstimulus intervals. We conclude that replenishment does not match the release of vesicles at mutant active zones in vivo and a sufficient standing RRP therefore cannot be maintained. We propose that otoferlin is involved in replenishing synaptic vesicles."],["dc.identifier.doi","10.1038/nn.2578"],["dc.identifier.gro","3142900"],["dc.identifier.isi","000279173900020"],["dc.identifier.pmid","20562868"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/355"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1097-6256"],["dc.title","Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]