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 8

AAV2/6-mediated expression of CatCh renders murine SGNs light sensitive.

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AAV2/6-mediated expression of CatCh renders murine SGNs light sensitive....
(A) Viral construct scheme. (B) Illustration of injection site on an embryo. Black, gray, and blue arrowheads indicate the fourth ventricle, primary head vein, and location of otocyst, respectively. (C) Cochlear section of a P7, AAV2/6-HSYN-CatCh-YFP–injected mouse; immunolabeling for Na/K-ATPase α3 subunit (red) and YFP (green) shows expression of CatCh in SGNs of the basal turn. Scale bar: 200 μm. (D) Magnification of C showing CatCh expression in SGN membranes. Scale bar: 20 μm. (E) Organ of Corti immunostaining shows extension of CatCh expression (YFP in green) in SGNs to the point where their neurites contact IHCs (calretinin in red). Scale bar: 20 μm. (F) Transduction of SGNs along the cochlear turns in positive animals (38% of injected animals were negative and are not shown). Markers for animals are maintained in the inset: oABR N1 amplitude correlates with transduction efficiency. (G) oABRs in response to 200-μs laser stimulation via an optical fiber inserted into the round window. (H) Precise and reliable spiking in a putative SGN in a CatCh-transfected mouse at stimulation rates up to at least 60 Hz (5-ms light pulses). (I) Quantification of first spiking response (indicated by arrows in H). Reliability of spiking (proportion of trials eliciting a spike during the stimulation time window) (top), mean first spike latencies (FSLs) (bottom left), and FSL variance (bottom right) in response to 5- to 10-ms flashes at different intensities. Grayscale values indicate seven different light-responsive neurons in the region of the AN and cochlear nucleus.