4.8 Article

Optogenetic stimulation of the auditory pathway

期刊

JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 3, 页码 1114-1129

出版社

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI69050

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资金

  1. German Federal Ministry of Education and Research [01GQ0810]
  2. German Research Foundation through the Center for Nanoscale Microscopy and Molecular Physiology of the Brain [FZT 103, SFB889]
  3. National Research Foundation, Singapore
  4. World Class Institute (WCI) Program of the National Research Foundation of Korea (NRF)
  5. Ministry of Education, Science and Technology of Korea (MEST) [NRF WCI 2009-003]
  6. Grants-in-Aid for Scientific Research [25250001, 25670103, 25115712, 25115701] Funding Source: KAKEN

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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.

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