Anttonen, Tommi Miikael

[["dc.bibliographiccitation.artnumber","ENEURO.0047"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","eNeuro"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Anttonen, Tommi"],["dc.contributor.author","Herranen, Anni"],["dc.contributor.author","Virkkala, Jussi"],["dc.contributor.author","Kirjavainen, Anna"],["dc.contributor.author","Elomaa, Pinja"],["dc.contributor.author","Laos, Maarja"],["dc.contributor.author","Liang, Xingqun"],["dc.contributor.author","Ylikoski, Jukka"],["dc.contributor.author","Behrens, Axel"],["dc.contributor.author","Pirvola, Ulla"],["dc.date.accessioned","2019-01-24T11:54:14Z"],["dc.date.available","2019-01-24T11:54:14Z"],["dc.date.issued","2016"],["dc.description.abstract","Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury-induced hair cell loss, but with unsolved mechanisms. We have characterized the c-Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells, and the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by nontraumatic noise levels and none of the cells showing this activation were lost, c-Jun phosphorylation is a biomarker for cochlear stress rather than an indicator of a death-prone fate of hair cells. Preconditioning with a mild noise exposure before a stronger traumatizing noise exposure attenuated the cochlear c-Jun stress response, suggesting that the known protective effect of sound preconditioning on hearing is linked to suppression of c-Jun activation. Finally, mice with mutations in the c-Jun N-terminal phosphoacceptor sites showed partial, but significant, hair cell protection. These data identify the c-Jun stress response as a paracrine mechanism that mediates outer hair cell death."],["dc.identifier.doi","10.1523/ENEURO.0047-16.2016"],["dc.identifier.pmid","27257624"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57359"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","2373-2822"],["dc.title","c-Jun N-Terminal Phosphorylation: Biomarker for Cellular Stress Rather than Cell Death in the Injured Cochlea"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Jean, Philippe"],["dc.contributor.author","Anttonen, Tommi"],["dc.contributor.author","Michanski, Susann"],["dc.contributor.author","de Diego, Antonio M. G."],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Oestreicher, David"],["dc.contributor.author","Kroll, Jana"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Ashmore, Jonathan"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:25:48Z"],["dc.date.available","2021-04-14T08:25:48Z"],["dc.date.issued","2020"],["dc.description.abstract","Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers presynaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding."],["dc.identifier.doi","10.1038/s41467-020-17003-z"],["dc.identifier.pmid","32587250"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81736"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/383"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Pangršič Vilfan (Experimental Otology)"],["dc.relation.workinggroup","RG Wichmann (Molecular Architecture of Synapses)"],["dc.rights","CC BY 4.0"],["dc.title","Macromolecular and electrical coupling between inner hair cells in the rodent cochlea"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]