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

Keppeler, D., Merino, R. M., de la Morena, D. L., Bali, B., Huet, A. T., Gehrt, A., et al. (2018). Ultrafast optogenetic stimulation of the auditory pathway by targeting-optimized Chronos. The EMBO Journal, 37(24): e99649. doi:10.15252/embj.201899649.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-7152-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-B80F-F
Genre: Journal Article

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 Creators:
Keppeler, D., Author
Merino, R. M., Author
de la Morena, D. L., Author
Bali, B., Author
Huet, A. T., Author
Gehrt, A., Author
Wrobel, C., Author
Subramanian, S., Author
Dombrowski, T., Author
Wolf, Fred1, Author              
Rankovic, V., Author
Neef, Andreas1, Author              
Moser, T., Author
Affiliations:
1Research Group Theoretical Neurophysics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063289              

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Free keywords: channelrhodopsin; cochlear implant; neural coding; spiral ganglion; trafficking
 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-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.

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Language(s): eng - English
 Dates: 2018-11-052018-12-14
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.15252/embj.201899649
 Degree: -

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Title: The EMBO Journal
Source Genre: Journal
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Pages: 15 Volume / Issue: 37 (24) Sequence Number: e99649 Start / End Page: - Identifier: -