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

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 6

Effects of stimulus properties on oABRs.

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Effects of stimulus properties on oABRs. (A) oABRs of 8 mice elicited by...
(A) oABRs of 8 mice elicited by focusing the light of an external power LED (5 ms, 4 mW/mm2 at 1 or 5 Hz) onto the cochleostomy. Symbols indicate N1. Gray line values identify the same mice across A and C–E, and symbols additionally aid the identification of mice throughout C–F. (B) oABR stimulation of increasing irradiance (3-ms pulse duration at 1 Hz) of an exemplary mouse. (C) Increase of N1 amplitude with radiant exposure (irradiances as in B; pulse duration of 2, 3, or 5 ms at 1 Hz). Group average is indicated by black filled circles. (D) Increase in N1 amplitude (normalized for maximum amplitude) with stimulus duration. (E) Latency of oABRs (defined as N1 passing through 0.1 mV) as a function of irradiance. Group average is indicated by black filled circles. (F) Decrease in N1 amplitude (normalized for maximum amplitude) with stimulus rate (black filled circles indicate group average).