Keppeler, Daniel

[["dc.bibliographiccitation.firstpage","35"],["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.lastpage","36"],["dc.bibliographiccitation.volume","213"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Wrobel, C."],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Gossler, Christian"],["dc.contributor.author","Schwarz, U. T."],["dc.contributor.author","Ruther, P."],["dc.contributor.author","Schwaerzle, M."],["dc.contributor.author","Hessler, R."],["dc.contributor.author","Salditt, Tim"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-11-07T09:59:50Z"],["dc.date.available","2018-11-07T09:59:50Z"],["dc.date.issued","2015"],["dc.identifier.isi","000362554200073"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37681"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.title","In vivo application of optogenetics in the auditory system"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","eabb8086"],["dc.bibliographiccitation.issue","553"],["dc.bibliographiccitation.journal","Science Translational Medicine"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Schwaerzle, Michael"],["dc.contributor.author","Harczos, Tamas"],["dc.contributor.author","Jablonski, Lukasz"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Wolf, Bettina"],["dc.contributor.author","Ayub, Suleman"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Wrobel, Christian"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Abdellatif, Khaled"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Paul, Oliver"],["dc.contributor.author","Ruther, Patrick"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-03-17T06:28:44Z"],["dc.date.available","2021-03-17T06:28:44Z"],["dc.date.issued","2020-07-22"],["dc.description.abstract","When hearing fails, electrical cochlear implants (eCIs) provide the brain with auditory information. One important bottleneck of CIs is the poor spectral selectivity that results from the wide current spread from each of the electrode contacts. Optical CIs (oCIs) promise to make better use of the tonotopic order of spiral ganglion neurons (SGNs) inside the cochlea by spatially confined stimulation. Here, we established multichannel oCIs based on light-emitting diode (LED) arrays and used them for optical stimulation of channelrhodopsin (ChR)-expressing SGNs in rodents. Power-efficient blue LED chips were integrated onto microfabricated 15-μm-thin polyimide-based carriers comprising interconnecting lines to address individual LEDs by a stationary or mobile driver circuitry. We extensively characterized the optoelectronic, thermal, and mechanical properties of the oCIs and demonstrated stability over weeks in vitro. We then implanted the oCIs into ChR-expressing rats and gerbils, and characterized multichannel optogenetic SGN stimulation by electrophysiological and behavioral experiments. Improved spectral selectivity was directly demonstrated by recordings from the auditory midbrain. Long-term experiments in deafened ChR-expressing rats and in nontreated control animals demonstrated specificity of optogenetic stimulation. Behavioral studies on animals carrying a wireless oCI sound processor revealed auditory percepts. This study demonstrates hearing restoration with improved spectral selectivity by an LED-based multichannel oCI system."],["dc.identifier.doi","10.1126/scitranslmed.abb8086"],["dc.identifier.pmid","32718992"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80539"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/57"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1946-6242"],["dc.relation.issn","1946-6234"],["dc.relation.orgunit","Institut für Auditorische Neurowissenschaften"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.title","Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents"],["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.artnumber","4922"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Gradl, Regine"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Vaßholz, Malte"],["dc.contributor.author","Meyer, Alexander"],["dc.contributor.author","Hessler, Roland"],["dc.contributor.author","Achterhold, Klaus"],["dc.contributor.author","Gleich, Bernhard"],["dc.contributor.author","Dierolf, Martin"],["dc.contributor.author","Pfeiffer, Franz"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-04-23T14:35:20Z"],["dc.date.available","2020-04-23T14:35:20Z"],["dc.date.issued","2018"],["dc.description.abstract","We demonstrate that phase retrieval and tomographic imaging at the organ level of small animals can be advantageously carried out using the monochromatic radiation emitted by a compact x-ray light source, without further optical elements apart from source and detector. This approach allows to carry out microtomography experiments which - due to the large performance gap with respect to conventional laboratory instruments - so far were usually limited to synchrotron sources. We demonstrate the potential by mapping the functional soft tissue within the guinea pig and marmoset cochlea, including in the latter case an electrical cochlear implant. We show how 3d microanatomical studies without dissection or microscopic imaging can enhance future research on cochlear implants."],["dc.identifier.doi","10.1038/s41598-018-23144-5"],["dc.identifier.pmid","29563553"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15421"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/64329"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.orgunit","Fakultät für Physik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Propagation-based phase-contrast x-ray tomography of cochlea using a compact synchrotron source"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","205401"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Journal of Physics D: Applied Physics"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Gossler, Christian"],["dc.contributor.author","Bierbrauer, Colin"],["dc.contributor.author","Moser, Ruediger"],["dc.contributor.author","Kunzer, Michael"],["dc.contributor.author","Holc, Katarzyna"],["dc.contributor.author","Pletschen, Wilfried"],["dc.contributor.author","Koehler, Klaus"],["dc.contributor.author","Wagner, Joachim"],["dc.contributor.author","Schwaerzle, Michael"],["dc.contributor.author","Ruther, Patrick"],["dc.contributor.author","Paul, Oliver"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Schwarz, Ulrich T."],["dc.date.accessioned","2017-09-07T11:46:14Z"],["dc.date.available","2017-09-07T11:46:14Z"],["dc.date.issued","2014"],["dc.description.abstract","Currently available cochlear implants are based on electrical stimulation of the spiral ganglion neurons. Optical stimulation with arrays of micro-sized light-emitting diodes (mu LEDs) promises to increase the number of distinguishable frequencies. Here, the development of a flexible GaN-based micro-LED array as an optical cochlear implant is reported for application in a mouse model. The fabrication of 15 mu m thin and highly flexible devices is enabled by a laser-based layer transfer process of the GaN-LEDs from sapphire to a polyimide-on-silicon carrier wafer. The fabricated 50 x 50 mu m(2) LEDs are contacted via conducting paths on both p- and n-sides of the LEDs. Up to three separate channels could be addressed. The probes, composed of a linear array of the said mu LEDs bonded to the flexible polyimide substrate, are peeled off the carrier wafer and attached to flexible printed circuit boards. Probes with four mu LEDs and a width of 230 mu m are successfully implanted in the mouse cochlea both in vitro and in vivo. The LEDs emit 60 mu W at 1 mA after peel-off, corresponding to a radiant emittance of 6 mW mm(-2)."],["dc.identifier.doi","10.1088/0022-3727/47/20/205401"],["dc.identifier.gro","3142121"],["dc.identifier.isi","000335517500011"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4777"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Iop Publishing Ltd"],["dc.relation.eissn","1361-6463"],["dc.relation.issn","0022-3727"],["dc.title","GaN-based micro-LED arrays on flexible substrates for optical cochlear implants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:27:00Z"],["dc.date.available","2021-04-14T08:27:00Z"],["dc.date.issued","2020"],["dc.description.abstract","Cochlear implants (CIs) are considered the most successful neuroprosthesis as they enable speech comprehension in the majority of half a million CI users suffering from sensorineural hearing loss. By electrically stimulating the auditory nerve, CIs constitute an interface re-connecting the brain and the auditory scene, providing the patient with information regarding the latter. However, since electric current is hard to focus in conductive environments such as the cochlea, the precision of electrical sound encoding—and thus quality of artificial hearing—is limited. Recently, optogenetic stimulation of the cochlea has been suggested as an alternative approach for hearing restoration. Cochlear optogenetics promises increased spectral selectivity of artificial sound encoding, hence improved hearing, as light can conveniently be confined in space to activate the auditory nerve within smaller tonotopic ranges. In this review, we discuss the latest experimental and technological developments of cochlear optogenetics and outline the remaining challenges on the way to clinical translation."],["dc.identifier.doi","10.15252/emmm.201911618"],["dc.identifier.pmid","32227585"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82138"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/190"],["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","CC BY 4.0"],["dc.title","Towards the optical cochlear implant: optogenetic approaches for hearing restoration"],["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","European Biophysics Journal"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Hernandez, Victor H."],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Wrobel, C."],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Gossler, C."],["dc.contributor.author","Schwaerzle, M."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Salditt, Tim"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Ruther, P."],["dc.contributor.author","Schwarz, U. T."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-11-07T09:55:33Z"],["dc.date.available","2018-11-07T09:55:33Z"],["dc.date.issued","2015"],["dc.identifier.isi","000380001400775"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36770"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.eventlocation","Dresden, GERMANY"],["dc.title","Employing optogenetics for auditory neuroscience and cochlear implants"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","eaao0540"],["dc.bibliographiccitation.issue","449"],["dc.bibliographiccitation.journal","Science Translational Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Wrobel, Christian"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Huet, Antoine"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2020-12-10T18:36:47Z"],["dc.date.available","2020-12-10T18:36:47Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1126/scitranslmed.aao0540"],["dc.identifier.eissn","1946-6242"],["dc.identifier.issn","1946-6234"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76736"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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"]]