Rankovic, Vladan

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Dörje, Nele M."],["dc.contributor.author","Bahader, Iman"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Thirumalai, Anupriya"],["dc.contributor.author","Weber, Thomas"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:29:50Z"],["dc.date.available","2021-04-14T08:29:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (\\u0026lt;5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches."],["dc.identifier.doi","10.3389/fnmol.2020.600051"],["dc.identifier.pmid","33488357"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83002"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/123"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["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.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Zabelskii, Dmitrii"],["dc.contributor.author","Alekseev, Alexey"],["dc.contributor.author","Kovalev, Kirill"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Balandin, Taras"],["dc.contributor.author","Soloviov, Dmytro"],["dc.contributor.author","Bratanov, Dmitry"],["dc.contributor.author","Savelyeva, Ekaterina"],["dc.contributor.author","Podolyak, Elizaveta"],["dc.contributor.author","Volkov, Dmytro"],["dc.contributor.author","Vaganova, Svetlana"],["dc.contributor.author","Astashkin, Roman"],["dc.contributor.author","Chizhov, Igor"],["dc.contributor.author","Yutin, Natalia"],["dc.contributor.author","Rulev, Maksim"],["dc.contributor.author","Popov, Alexander"],["dc.contributor.author","Eria-Oliveira, Ana-Sofia"],["dc.contributor.author","Rokitskaya, Tatiana"],["dc.contributor.author","Mager, Thomas"],["dc.contributor.author","Antonenko, Yuri"],["dc.contributor.author","Rosselli, Riccardo"],["dc.contributor.author","Armeev, Grigoriy"],["dc.contributor.author","Shaitan, Konstantin"],["dc.contributor.author","Vivaudou, Michel"],["dc.contributor.author","Büldt, Georg"],["dc.contributor.author","Rogachev, Andrey"],["dc.contributor.author","Rodriguez-Valera, Francisco"],["dc.contributor.author","Kirpichnikov, Mikhail"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Offenhäusser, Andreas"],["dc.contributor.author","Willbold, Dieter"],["dc.contributor.author","Koonin, Eugene"],["dc.contributor.author","Bamberg, Ernst"],["dc.contributor.author","Gordeliy, Valentin"],["dc.date.accessioned","2021-04-14T08:31:48Z"],["dc.date.available","2021-04-14T08:31:48Z"],["dc.date.issued","2020"],["dc.description.abstract","Phytoplankton is the base of the marine food chain as well as oxygen and carbon cycles and thus plays a global role in climate and ecology. Nucleocytoplasmic Large DNA Viruses that infect phytoplankton organisms and regulate the phytoplankton dynamics encompass genes of rhodopsins of two distinct families. Here, we present a functional and structural characterization of two proteins of viral rhodopsin group 1, OLPVR1 and VirChR1. Functional analysis of VirChR1 shows that it is a highly selective, Na+/K+-conducting channel and, in contrast to known cation channelrhodopsins, it is impermeable to Ca2+ ions. We show that, upon illumination, VirChR1 is able to drive neural firing. The 1.4 Å resolution structure of OLPVR1 reveals remarkable differences from the known channelrhodopsins and a unique ion-conducting pathway. Thus, viral rhodopsins 1 represent a unique, large group of light-gated channels (viral channelrhodopsins, VirChR1s). In nature, VirChR1s likely mediate phototaxis of algae enhancing the host anabolic processes to support virus reproduction, and therefore, might play a major role in global phytoplankton dynamics. Moreover, VirChR1s have unique potential for optogenetics as they lack possibly noxious Ca2+ permeability."],["dc.identifier.doi","10.1038/s41467-020-19457-7"],["dc.identifier.pmid","33177509"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83717"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/91"],["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 Mager (Advanced Optogenes)"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","CC BY 4.0"],["dc.title","Viral rhodopsins 1 are an unique family of light-gated cation channels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Oestreicher, David"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Pangrsic, Tina"],["dc.date.accessioned","2021-10-01T09:58:18Z"],["dc.date.available","2021-10-01T09:58:18Z"],["dc.date.issued","2021"],["dc.description.abstract","Clinical management of auditory synaptopathies like other genetic hearing disorders is currently limited to the use of hearing aids or cochlear implants. However, future gene therapy promises restoration of hearing in selected forms of monogenic hearing impairment, in which cochlear morphology is preserved over a time window that enables intervention. This includes non-syndromic autosomal recessive hearing impairment DFNB93, caused by defects in the CABP2 gene. Calcium-binding protein 2 (CaBP2) is a potent modulator of inner hair cell (IHC) voltage-gated calcium channels Ca V 1.3. Based on disease modeling in Cabp2 –/– mice, DFNB93 hearing impairment has been ascribed to enhanced steady-state inactivation of IHC Ca V 1.3 channels, effectively limiting their availability to trigger synaptic transmission. This, however, does not seem to interfere with cochlear development and does not cause early degeneration of hair cells or their synapses. Here, we studied the potential of a gene therapeutic approach for the treatment of DFNB93. We used AAV2/1 and AAV-PHP.eB viral vectors to deliver the Cabp2 coding sequence into IHCs of early postnatal Cabp2 –/– mice and assessed the level of restoration of hair cell function and hearing. Combining in vitro and in vivo approaches, we observed high transduction efficiency, and restoration of IHC Ca V 1.3 function resulting in improved hearing of Cabp2 –/– mice. These preclinical results prove the feasibility of DFNB93 gene therapy."],["dc.description.abstract","Clinical management of auditory synaptopathies like other genetic hearing disorders is currently limited to the use of hearing aids or cochlear implants. However, future gene therapy promises restoration of hearing in selected forms of monogenic hearing impairment, in which cochlear morphology is preserved over a time window that enables intervention. This includes non-syndromic autosomal recessive hearing impairment DFNB93, caused by defects in the CABP2 gene. Calcium-binding protein 2 (CaBP2) is a potent modulator of inner hair cell (IHC) voltage-gated calcium channels Ca V 1.3. Based on disease modeling in Cabp2 –/– mice, DFNB93 hearing impairment has been ascribed to enhanced steady-state inactivation of IHC Ca V 1.3 channels, effectively limiting their availability to trigger synaptic transmission. This, however, does not seem to interfere with cochlear development and does not cause early degeneration of hair cells or their synapses. Here, we studied the potential of a gene therapeutic approach for the treatment of DFNB93. We used AAV2/1 and AAV-PHP.eB viral vectors to deliver the Cabp2 coding sequence into IHCs of early postnatal Cabp2 –/– mice and assessed the level of restoration of hair cell function and hearing. Combining in vitro and in vivo approaches, we observed high transduction efficiency, and restoration of IHC Ca V 1.3 function resulting in improved hearing of Cabp2 –/– mice. These preclinical results prove the feasibility of DFNB93 gene therapy."],["dc.identifier.doi","10.3389/fnmol.2021.689415"],["dc.identifier.pmid","34489639"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90035"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/418"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.publisher","Frontiers Media S.A."],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Pangršič Vilfan (Experimental Otology)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Cabp2-Gene Therapy Restores Inner Hair Cell Calcium Currents and Improves Hearing in a DFNB93 Mouse Model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["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.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Huet, Antoine Tarquin"],["dc.contributor.author","Dombrowski, Tobias"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Thirumalai, Anupriya"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:27:59Z"],["dc.date.available","2021-04-14T08:27:59Z"],["dc.date.issued","2021"],["dc.description.abstract","Optogenetic stimulation of type I spiral ganglion neurons (SGNs) promises an alternative to the electrical stimulation by current cochlear implants (CIs) for improved hearing restoration by future optical CIs (oCIs). Most of the efforts in using optogenetic stimulation in the cochlea so far used early postnatal injection of viral vectors carrying blue-light activated channelrhodopsins (ChRs) into the cochlea of mice. However, preparing clinical translation of the oCI requires (i) reliable and safe transduction of mature SGNs of further species and (ii) use of long-wavelength light to avoid phototoxicity. Here, we employed a fast variant of the red-light activated channelrhodopsin Chrimson (f-Chrimson) and different AAV variants to implement optogenetic SGN stimulation in Mongolian gerbils. We compared early postnatal (p8) and adult (\\u0026gt;8 weeks) AAV administration, employing different protocols for injection of AAV-PHP.B and AAV2/6 into the adult cochlea. Success of the optogenetic manipulation was analyzed by optically evoked auditory brainstem response (oABR) and immunohistochemistry of mid-modiolar cryosections of the cochlea. In order to most efficiently evaluate the immunohistochemical results a semi-automatic procedure to identify transduced cells in confocal images was developed. Our results indicate that the rate of SGN transduction is significantly lower for AAV administration into the adult cochlea compared to early postnatal injection. SGN transduction upon AAV administration into the adult cochlea was largely independent of the chosen viral vector and injection approach. The higher the rate of SGN transduction, the lower were oABR thresholds and the larger were oABR amplitudes. Our results highlight the need to optimize viral vectors and virus administration for efficient optogenetic manipulation of SGNs in the adult cochlea for successful clinical translation of SGN-targeting gene therapy and of the oCI."],["dc.identifier.doi","10.3389/fnmol.2021.635897"],["dc.identifier.pmid","33776648"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82465"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/305"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["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"]]

[["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Klein, Eric"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Jablonski, Lukasz"],["dc.contributor.author","Harczos, Tamas"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Paul, Oliver"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Ruther, Patrick"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:25:11Z"],["dc.date.available","2021-04-14T08:25:11Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Electrical cochlear implants (eCIs) partially restore hearing and enable speech comprehension to more than half a million users, thereby re‐connecting deaf patients to the auditory scene surrounding them. Yet, eCIs suffer from limited spectral selectivity, resulting from current spread around each electrode contact and causing poor speech recognition in the presence of background noise. Optogenetic stimulation of the auditory nerve might overcome this limitation as light can be conveniently confined in space. Here, we combined virus‐mediated optogenetic manipulation of cochlear spiral ganglion neurons (SGNs) and microsystems engineering to establish acute multi‐channel optical cochlear implant (oCI) stimulation in adult Mongolian gerbils. oCIs based on 16 microscale thin‐film light‐emitting diodes (μLEDs) evoked tonotopic activation of the auditory pathway with high spectral selectivity and modest power requirements in hearing and deaf gerbils. These results prove the feasibility of μLED‐based oCIs for spectrally selective activation of the auditory nerve."],["dc.description.abstract","Synopsis image Electrical cochlear implants effectiveness in individuals remains limited by the spread of the electric current in the cochlea. This study explores the potential of optogenetics for hearing restoration through combining optogenetic manipulation of the auditory nerve with microsystems engineering. μLED‐based optical cochlear implants (oCI) enable stimulation of the rodent auditory nerve. The strength of induced responses scales with the number of recruited emitters. μLED‐evoked neural responses are tonotopic and spectrally selective. The combination of gene therapy and microsystems engineering enables optical activation of the auditory nerve with higher spectral precision in gerbils."],["dc.description.abstract","Electrical cochlear implants effectiveness in individuals remains limited by the spread of the electric current in the cochlea. This study explores the potential of optogenetics for hearing restoration through combining optogenetic manipulation of the auditory nerve with microsystems engineering. image"],["dc.description.sponsorship","H2020 European Research Council (ERC) http://dx.doi.org/10.13039/100010663"],["dc.description.sponsorship","Bundesministerium für Bildung und Forschung (BMBF) http://dx.doi.org/10.13039/501100002347"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.15252/emmm.202012387"],["dc.identifier.pmid","32596983"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81549"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/52"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1757-4684"],["dc.relation.issn","1757-4676"],["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 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","μLED‐based optical cochlear implants for spectrally selective activation of the auditory nerve"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1962"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2019-07-09T11:51:25Z"],["dc.date.available","2019-07-09T11:51:25Z"],["dc.date.issued","2019"],["dc.description.abstract","Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) and partially restore hearing to half a million CI users. However, wide current spread from intracochlear electrodes limits spatial selectivity (i.e. spectral resolution) of electrical CIs. Optogenetic stimulation might become an alternative, since light can be confined in space, promising artificial sound encoding with increased spectral selectivity. Here we compare spectral selectivity of optogenetic, electric, and acoustic stimulation by multi-channel recordings in the inferior colliculus (IC) of gerbils. When projecting light onto tonotopically distinct SGNs, we observe corresponding tonotopically ordered IC activity. An activity-based comparison reveals that spectral selectivity of optogenetic stimulation is indistinguishable from acoustic stimulation for modest intensities. Moreover, optogenetic stimulation outperforms bipolar electric stimulation at medium and high intensities and monopolar electric stimulation at all intensities. In conclusion, we demonstrate better spectral selectivity of optogenetic over electric SGN stimulation, suggesting the potential for improved hearing restoration by optical CIs."],["dc.identifier.doi","10.1038/s41467-019-09980-7"],["dc.identifier.pmid","31036812"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16124"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59945"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/H2020/670759/EU//OptoHear"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Near physiological spectral selectivity of cochlear optogenetics"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1750"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Mager, Thomas"],["dc.contributor.author","Lopez de la Morena, David"],["dc.contributor.author","Senn, Verena"],["dc.contributor.author","Schlotte, Johannes"],["dc.contributor.author","D´Errico, Anna"],["dc.contributor.author","Feldbauer, Katrin"],["dc.contributor.author","Wrobel, Christian"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Bodensiek, Kai"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Browne, Lorcan"],["dc.contributor.author","Huet, Antoine"],["dc.contributor.author","Jüttner, Josephine"],["dc.contributor.author","Wood, Phillip G"],["dc.contributor.author","Letzkus, Johannes J."],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Bamberg, Ernst"],["dc.date.accessioned","2018-07-12T06:58:57Z"],["dc.date.available","2018-07-12T06:58:57Z"],["dc.date.issued","2018"],["dc.description.abstract","Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration."],["dc.identifier.doi","10.1038/s41467-018-04146-3"],["dc.identifier.pmid","29717130"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15178"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","2041-1723"],["dc.relation.eissn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]