Rankovic, Vladan

[["dc.bibliographiccitation.artnumber","e99649"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Merino, Ricardo Martins"],["dc.contributor.author","Lopez de la Morena, David"],["dc.contributor.author","Bali, Burak"],["dc.contributor.author","Huet, Antoine Tarquin"],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Wrobel, Christian"],["dc.contributor.author","Subramanian, Swati"],["dc.contributor.author","Dombrowski, Tobias"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2019-07-09T11:51:47Z"],["dc.date.available","2019-07-09T11:51:47Z"],["dc.date.issued","2018"],["dc.description.abstract","Optogenetic tools, providing non‐invasive control over selected cells, have the potential to revolutionize sensory prostheses for humans. Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. However, most channelrhodopsins do not support the high temporal fidelity pertinent to auditory coding because they require milliseconds to close after light‐off. Here, we biophysically characterized the fast channelrhodopsin Chronos and revealed a deactivation time constant of less than a millisecond at body temperature. In order to enhance neural expression, we improved its trafficking to the plasma membrane (Chronos‐ES/TS). Following efficient transduction of SGNs using early postnatal injection of the adeno‐associated virus AAV‐PHP.B into the mouse cochlea, fiber‐based optical stimulation elicited optical auditory brainstem responses (oABR) with minimal latencies of 1 ms, thresholds of 5 μJ and 100 μs per pulse, and sizable amplitudes even at 1,000 Hz of stimulation. Recordings from single SGNs demonstrated good temporal precision of light‐evoked spiking. In conclusion, efficient virus‐mediated expression of targeting‐optimized Chronos‐ES/TS achieves ultrafast optogenetic control of neurons."],["dc.identifier.doi","10.15252/embj.201899649"],["dc.identifier.pmid","30396994"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60011"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","submitted_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e202101338"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Life Science Alliance"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Bali, Burak"],["dc.contributor.author","Gruber-Dujardin, Eva"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2022-06-01T09:39:47Z"],["dc.date.available","2022-06-01T09:39:47Z"],["dc.date.issued","2022"],["dc.description.abstract","AAV-mediated optogenetic neural stimulation has become a clinical approach for restoring function in sensory disorders and feasibility for hearing restoration has been indicated in rodents. Nonetheless, long-term stability and safety of AAV-mediated channelrhodopsin (ChR) expression in spiral ganglion neurons (SGNs) remained to be addressed. Here, we used longitudinal studies on mice subjected to early postnatal administration of AAV2/6 carrying fast gating ChR f-Chrimson under the control of the human synapsin promoter unilaterally to the cochlea. f-Chrimson expression in SGNs in both ears and the brain was probed in animals aged 1 mo to 2 yr. f-Chrimson was observed in SGNs at all ages indicating longevity of ChR-expression. SGN numbers in the AAV-injected cochleae declined with age faster than in controls. Investigations were extended to the brain in which viral transduction was observed across the organ at varying degrees irrespective of age without observing viral spread-related pathologies. No viral DNA or virus-related histopathological findings in visceral organs were encountered. In summary, our study demonstrates life-long (24 mo in mice) expression of f-Chrimson in SGNs upon single AAV-dosing of the cochlea."],["dc.description.sponsorship","European Research Council"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Fondation Pour l’Audition"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.26508/lsa.202101338"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108563"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/481"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2575-1077"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Bali, Burak"],["dc.contributor.author","Lopez de la Morena, David"],["dc.contributor.author","Mittring, Artur"],["dc.contributor.author","Mager, Thomas"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Huet, Antoine Tarquin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-06-01T09:42:20Z"],["dc.date.available","2021-06-01T09:42:20Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we employed fast and very fast variants of the red‐light‐activated channelrhodopsin (ChR) Chrimson (f‐Chrimson and vf‐Chrimson) to study their utility for optogenetic stimulation of SGNs in mice. The light requirements were higher for vf‐Chrimson than for f‐Chrimson, even when optimizing membrane expression of vf‐Chrimson by adding potassium channel trafficking sequences. Optogenetic time and intensity coding by single putative SGNs were compared with coding of acoustic clicks. vf‐Chrimson enabled putative SGNs to fire at near‐physiological rates with good temporal precision up to 250 Hz of stimulation. The dynamic range of SGN spike rate coding upon optogenetic stimulation was narrower than for acoustic clicks but larger than reported for electrical stimulation. The dynamic range of spike timing, on the other hand, was more comparable for optogenetic and acoustic stimulation. In conclusion, f‐Chrimson and vf‐Chrimson are promising candidates for optogenetic stimulation of SGNs in auditory research and future cochlear implants."],["dc.description.abstract","Synopsis image Identifying suitable channelrhodopsins is crucial for future optogenetic restoration of sound encoding by optical cochlear implants. Here, fast and very fast light‐activated Chrimsons were compared for their utility to optogenetically encode timing and intensity information in the auditory nerve. Very fast Chrimson increases temporal fidelity but confers lower light sensitivity of optogenetic auditory nerve fiber stimulation compared with fast Chrimson. Adding trafficking sequences of the inwardly rectifying potassium channel 2.1 improved plasma membrane expression of very fast Chrimson enabling shorter stimulus durations The dynamic range, based on the discharge rate, of optogenetic auditory nerve fiber stimulation was narrower than that of acoustic stimulation. The dynamic range, based on temporal precision of spiking, of optogenetic auditory nerve fiber stimulation was broader than that based on discharge rate."],["dc.description.abstract","Identifying suitable channelrhodopsins is crucial for future optogenetic restoration of sound encoding by optical cochlear implants. Here, fast and very fast light‐activated Chrimson were compared for their utility to optogenetically encode timing and intensity information in the auditory nerve. image"],["dc.description.sponsorship","EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)"],["dc.description.sponsorship","Cluster of Excellence; Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells; (MBExC) Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)"],["dc.description.sponsorship","Leibniz Program"],["dc.description.sponsorship","Göttingen Promotionkolleg für Medizinstudierende"],["dc.identifier.doi","10.15252/emmm.202013391"],["dc.identifier.pmid","33960685"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85221"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/255"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1757-4684"],["dc.relation.issn","1757-4676"],["dc.relation.workinggroup","RG Mager (Advanced Optogenes)"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Utility of red‐light ultrafast optogenetic stimulation of the auditory pathway"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]