Optogenetic stimulation of the auditory pathway
Victor H. Hernandez, … , Nicola Strenzke, Tobias Moser
Victor H. Hernandez, … , Nicola Strenzke, Tobias Moser
Published February 10, 2014
Citation Information: J Clin Invest. 2014;124(3):1114-1129. https://doi.org/10.1172/JCI69050.
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Optogenetic stimulation of the auditory pathway

Abstract

Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics.

Authors

Victor H. Hernandez, Anna Gehrt, Kirsten Reuter, Zhizi Jing, Marcus Jeschke, Alejandro Mendoza Schulz, Gerhard Hoch, Matthias Bartels, Gerhard Vogt, Carolyn W. Garnham, Hiromu Yawo, Yugo Fukazawa, George J. Augustine, Ernst Bamberg, Sebastian Kügler, Tim Salditt, Livia de Hoz, Nicola Strenzke, Tobias Moser

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Figure 2

Specificity of oABRs for ChR2-mediated activation of the auditory pathway.

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Specificity of oABRs for ChR2-mediated activation of the auditory pathwa...
(A) No oABRs upon projection of light onto the cochleostomy of a wild-type mouse. (B) No oABRs upon projection of light onto the cochlea prior to cochleostomy of a ChR2 transgenic mouse (stimulus artifacts are absent because of careful positioning of the cables connected to the needle electrodes) and oABRs present after cochleostomy. (C and D) oABRs before and after placing a mini-gelfoam containing the sodium channel blocker lidocaine (C, 20 minutes of gelfoam application) or TTX (D, 63 minutes of gelfoam application) onto the cochleostomy. (E) Loss of oABRs evoked by projection of light onto the cochleostomy (ChR2 mouse) after sacrificing with an overdose of ketamine (as evident from zero-line ECG). (F) oABRs of a ChR2 mouse before and after severing the facial nerve (CN VII). Inset shows the light-evoked facial electromyogram (EMG), before and after dissecting the nerve. Stimulus: blue light power LED; 4 mW/mm2 at the indicated duration at 1 Hz; 50 trials for all panels.