Format

Send to

Choose Destination
EMBO J. 2018 Dec 14;37(24). pii: e99649. doi: 10.15252/embj.201899649. Epub 2018 Nov 5.

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

Keppeler D1,2, Merino RM2,3,4,5, Lopez de la Morena D1,2,6, Bali B1,2,7, Huet AT1,3,6, Gehrt A1,8, Wrobel C1,8, Subramanian S1,2, Dombrowski T1, Wolf F4,5,8,9,10, Rankovic V11,7, Neef A12,4,10, Moser T11,2,3,5,6,8,13.

Author information

1
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
2
Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, Göttingen, Germany.
3
Biophysics of Neural Computation Group, Bernstein Center for Computational Neuroscience Göttingen, Göttingen, Germany.
4
Neurophysics Group, Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany.
5
Max Planck Institute for Experimental Medicine, Göttingen, Germany.
6
Auditory Neuroscience and Optogenetics Laboratory, German Primate Center, Göttingen, Germany.
7
Restorative Cochlear Genomics Group, German Primate Center, Göttingen, Germany.
8
Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
9
Bernstein Center for Computational Neuroscience, Göttingen, Germany.
10
Campus Institute for Dynamics of Biological Networks, Göttingen, Germany.
11
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany vrankovic@dpz.eu andreas@nld.ds.mpg.de tmoser@gwdg.de.
12
Biophysics of Neural Computation Group, Bernstein Center for Computational Neuroscience Göttingen, Göttingen, Germany vrankovic@dpz.eu andreas@nld.ds.mpg.de tmoser@gwdg.de.
13
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.

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.

KEYWORDS:

channelrhodopsin; cochlear implant; neural coding; spiral ganglion; trafficking

PMID:
30396994
PMCID:
PMC6293277
[Available on 2019-12-14]
DOI:
10.15252/embj.201899649
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center