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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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Technical Advance Otology

Optogenetic stimulation of the auditory pathway

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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 4

Interaction of optogenetic and acoustic cochlear stimulation.

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Interaction of optogenetic and acoustic cochlear stimulation.
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(A) Following careful cochleostomy and positioning of a μLED, regular and light-masked acoustic thresholds were estimated by application of tone bursts of varying sound pressure levels (SPLs) and frequencies in the absence of optical stimulation (black) or following the cessation of an oABR that occurred at the onset of a concomitant 40-ms light stimulation (red). (B) Average aABR audiogram of four cochleostomized mice (best threshold not exceeding 70 dB) in the absence (black) and presence (red) of concomitant light; threshold increase upon light indicates masking due to a preceding optogenetic stimulation of the same population of neurons. (C) Tomography of an explanted mouse cochlea based on cone-beam in-line phase contrast at a compact laboratory x-ray source and a fast phase reconstruction procedure. Bony structures were segmented automatically; the basilar membrane (green), Rosenthal’s canal (blue), and cochleostomy (gray) were traced with semiautomatic segmentation. A spline curve was fitted to the basilar membrane and was used to identify the position of the cochleostomy relative to the tonotopic map of the cochlea (D, modified from ref. 36). See Methods for further description. (E) Light-on-tone masking assessed as the change in P1–N1 aABR amplitude with simultaneous μLED stimulation.
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ISSN: 0021-9738 (print), 1558-8238 (online)

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