Utility of red‐light ultrafast optogenetic stimulation of the auditory pathway

2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Utility of red‐light ultrafast optogenetic stimulation of the auditory pathway​
Bali, B.; Lopez de la Morena, D.; Mittring, A.; Mager, T. ; Rankovic, V.; Huet, A. T. & Moser, T. ​ (2021) 
EMBO Molecular Medicine13(6).​ DOI: https://doi.org/10.15252/emmm.202013391 

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Authors
Bali, Burak; Lopez de la Morena, David; Mittring, Artur; Mager, Thomas ; Rankovic, Vladan; Huet, Antoine Tarquin; Moser, Tobias 
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.
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.
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
Issue Date
2021
Journal
EMBO Molecular Medicine 
Project
EXC 2067: Multiscale Bioimaging 
Working Group
RG Mager (Advanced Optogenes) 
RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding) 
External URL
https://mbexc.uni-goettingen.de/literature/publications/255
ISSN
1757-4676
eISSN
1757-4684
Language
English
Sponsor
EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
Cluster of Excellence; Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells; (MBExC) Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Leibniz Program
Göttingen Promotionkolleg für Medizinstudierende

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