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Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos
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, m...
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Published in: | The EMBO journal 2018-12, Vol.37 (24), p.n/a |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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.
Synopsis
Here we biophysically characterized and molecularly improved the fast gating blue‐light activated channelrhodopsin Chronos. Employing the potent viral vector AAV‐PHP.B we postnatally expressed the improved Chronos in cochlear neurons and achieved ultrafast neural control.
Biophysical characterization of the fast channelrhodopsin Chronos revealed a deactivation time constant of less than a millisecond at body temperature.
Molecular engineering of Chronos via adding trafficking sequences enhanced plasma membrane abundance of the opsin and use of postnatal AAV‐PHP.B carrying Chronos into the mouse cochlea enabled efficient expression in spiral ganglion neurons.
Chronos enabled synchronized optically driven firing in spiral ganglion neurons for stimulation rates of up to hundreds of Hz as required for future optical cochlear implants.
Graphical Abstract
Biophysical characterization and molecular engineering of the fast channelrhodopsin Chronos results in a new optogentics tool for controlling fast neural circuitries with high temporal fidelity. |
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ISSN: | 0261-4189 1460-2075 |
DOI: | 10.15252/embj.201899649 |