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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 5

Assessment of the spread of cochlear excitation during optogenetic, acoustic, and electrical stimulation with multielectrode array recordings in the IC.

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Assessment of the spread of cochlear excitation during optogenetic, acou...
(A) Surgical site with recording electrode inserted into the right ICC. SSS, superior sagittal sinus; TS, transverse sinus; CB, cerebellum. (B–D) False color–coded representative profiles of LFPs evoked by optical (B), acoustic (C), and electrical (D) stimulation, recorded with multielectrode arrays. Note that the absolute depth (ordinate) differs between B–D, because maximum responses were found in different IC layers. Dashed lines indicate stimulus duration. (E) Profiles of LFPs were transformed into CSD patterns via the second spatial derivative (42). (F–H) Illustrative CSD patterns after optical, acoustic, and electrical stimulation, respectively. Sinks are plotted in blue and sources in red. Significant sinks are outlined in black, with centroid and peak highlighted by black and white open circles. Note that multiple sinks were usually identified for electrical stimulation. (I) Schematic representation of the tonotopic map of a mouse IC (modified from ref. 37). Average recording depth (black squares) at which the sinks were identified was plotted at estimated electrode positions. A, acoustic; O, optical; E, electrical stimulation. (J–L) Characterization of sinks for the three different stimulation modalities. If several sinks were found, the sink with the largest total charge was used for further analysis. (J) Maximum spatial extents and recording depth at which the sink was found. (K) Peak latencies. (L) Total carried charge. The green bar indicates the charge carried by all sinks.
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