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Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos

dc.contributor.authorKeppeler, Daniel
dc.contributor.authorMerino, Ricardo Martins
dc.contributor.authorLopez de la Morena, David
dc.contributor.authorBali, Burak
dc.contributor.authorHuet, Antoine Tarquin
dc.contributor.authorGehrt, Anna
dc.contributor.authorWrobel, Christian
dc.contributor.authorSubramanian, Swati
dc.contributor.authorDombrowski, Tobias
dc.contributor.authorWolf, Fred
dc.contributor.authorRankovic, Vladan
dc.contributor.authorNeef, Andreas
dc.contributor.authorMoser, Tobias
dc.date.accessioned2019-06-12T07:37:42Z
dc.date.available2019-06-12T07:37:42Z
dc.date.issued2018de
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/16193
dc.description.abstractOptogenetic 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.de
dc.language.isoengde
dc.rightsopenAccess
dc.subjectChannelrhodopsin; Cochlear Implant; Neural Coding; Spiral Ganglion; Traffickingde
dc.subject.ddc610
dc.titleUltrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronosde
dc.typejournalArticlede
dc.identifier.doi10.15252/embj.201899649
dc.type.versionsubmittedVersionde
dc.relation.pISSN0261-4189
dc.relation.eISSN1460-2075
dc.bibliographicCitation.volume37de
dc.bibliographicCitation.issue24de
dc.type.subtypejournalArticle
dc.identifier.pmid30396994
dc.bibliographicCitation.articlenumbere99649de
dc.description.statuspeerReviewedde
dc.bibliographicCitation.journalThe EMBO Journalde


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