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

Daniel Keppeler, Ricardo Martins Merino, David Lopez de la Morena, Burak Bali, Antoine Tarquin Huet, Anna Gehrt, Christian Wrobel, Swati Subramanian, Tobias Dombrowski, Fred Wolf, Vladan Rankovic, Andreas Neef (+1 others)
<span title="2018-11-05">2018</span> <i title="EMBO"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/xcjlfiweh5bfpiome6ieuwel2a" style="color: black;">EMBO Journal</a> </i> &nbsp;
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
more &raquo; ... hannelrhodopsin 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-PHPB 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.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.15252/embj.201899649">doi:10.15252/embj.201899649</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/30396994">pmid:30396994</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC6293277/">pmcid:PMC6293277</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/5p5z3bkbnzfr3ibxwk4xh2aygi">fatcat:5p5z3bkbnzfr3ibxwk4xh2aygi</a> </span>
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