Hearing loss controlled by optogenetic stimulation of nonexcitable nonglial cells in the cochlea of the inner ear

Mitsuo P. Sato, Taiga Higuchi, Fumiaki Nin, Genki Ogata, Seishiro Sawamura, Takamasa Yoshida, Takeru Ota, Karin Hori, Shizuo Komune, Satoru Uetsuka, Samuel Choi, Masatsugu Masuda, Takahisa Watabe, Sho Kanzaki, Kaoru Ogawa, Hidenori Inohara, Shuichi Sakamoto, Hirohide Takebayashi, Katsumi Doi, Kenji F. TanakaHiroshi Hibino

Research output: Contribution to journalArticle

Abstract

Light-gated ion channels and transporters have been applied to a broad array of excitable cells including neurons, cardiac myocytes, skeletal muscle cells and pancreatic β-cells in an organism to clarify their physiological and pathological roles. Nonetheless, among nonexcitable cells, only glial cells have been studied in vivo by this approach. Here, by optogenetic stimulation of a different nonexcitable cell type in the cochlea of the inner ear, we induce and control hearing loss. To our knowledge, deafness animal models using optogenetics have not yet been established. Analysis of transgenic mice expressing channelrhodopsin-2 (ChR2) induced by an oligodendrocyte-specific promoter identified this channel in nonglial cells—melanocytes—of an epithelial-like tissue in the cochlea. The membrane potential of these cells underlies a highly positive potential in a K+-rich extracellular solution, endolymph; this electrical property is essential for hearing. Illumination of the cochlea to activate ChR2 and depolarize the melanocytes significantly impaired hearing within a few minutes, accompanied by a reduction in the endolymphatic potential. After cessation of the illumination, the hearing thresholds and potential returned to baseline during several minutes. These responses were replicable multiple times. ChR2 was also expressed in cochlear glial cells surrounding the neuronal components, but slight neural activation caused by the optical stimulation was unlikely to be involved in the hearing impairment. The acute-onset, reversible and repeatable phenotype, which is inaccessible to conventional gene-targeting and pharmacological approaches, seems to at least partially resemble the symptom in a population of patients with sensorineural hearing loss. Taken together, this mouse line may not only broaden applications of optogenetics but also contribute to the progress of translational research on deafness.

Original languageEnglish
Article number300
JournalFrontiers in Molecular Neuroscience
Volume10
DOIs
Publication statusPublished - Sep 21 2017

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Optogenetics
Cochlea
Inner Ear
Hearing Loss
Hearing
Deafness
Lighting
Neuroglia
Endolymph
Translational Medical Research
Gene Targeting
Sensorineural Hearing Loss
Melanocytes
Oligodendroglia
Ion Channels
Cardiac Myocytes
Membrane Potentials
Muscle Cells
Transgenic Mice
Skeletal Muscle

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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Hearing loss controlled by optogenetic stimulation of nonexcitable nonglial cells in the cochlea of the inner ear. / Sato, Mitsuo P.; Higuchi, Taiga; Nin, Fumiaki; Ogata, Genki; Sawamura, Seishiro; Yoshida, Takamasa; Ota, Takeru; Hori, Karin; Komune, Shizuo; Uetsuka, Satoru; Choi, Samuel; Masuda, Masatsugu; Watabe, Takahisa; Kanzaki, Sho; Ogawa, Kaoru; Inohara, Hidenori; Sakamoto, Shuichi; Takebayashi, Hirohide; Doi, Katsumi; Tanaka, Kenji F.; Hibino, Hiroshi.

In: Frontiers in Molecular Neuroscience, Vol. 10, 300, 21.09.2017.

Research output: Contribution to journalArticle

Sato, MP, Higuchi, T, Nin, F, Ogata, G, Sawamura, S, Yoshida, T, Ota, T, Hori, K, Komune, S, Uetsuka, S, Choi, S, Masuda, M, Watabe, T, Kanzaki, S, Ogawa, K, Inohara, H, Sakamoto, S, Takebayashi, H, Doi, K, Tanaka, KF & Hibino, H 2017, 'Hearing loss controlled by optogenetic stimulation of nonexcitable nonglial cells in the cochlea of the inner ear', Frontiers in Molecular Neuroscience, vol. 10, 300. https://doi.org/10.3389/fnmol.2017.00300
Sato, Mitsuo P. ; Higuchi, Taiga ; Nin, Fumiaki ; Ogata, Genki ; Sawamura, Seishiro ; Yoshida, Takamasa ; Ota, Takeru ; Hori, Karin ; Komune, Shizuo ; Uetsuka, Satoru ; Choi, Samuel ; Masuda, Masatsugu ; Watabe, Takahisa ; Kanzaki, Sho ; Ogawa, Kaoru ; Inohara, Hidenori ; Sakamoto, Shuichi ; Takebayashi, Hirohide ; Doi, Katsumi ; Tanaka, Kenji F. ; Hibino, Hiroshi. / Hearing loss controlled by optogenetic stimulation of nonexcitable nonglial cells in the cochlea of the inner ear. In: Frontiers in Molecular Neuroscience. 2017 ; Vol. 10.
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AU - Sawamura, Seishiro

AU - Yoshida, Takamasa

AU - Ota, Takeru

AU - Hori, Karin

AU - Komune, Shizuo

AU - Uetsuka, Satoru

AU - Choi, Samuel

AU - Masuda, Masatsugu

AU - Watabe, Takahisa

AU - Kanzaki, Sho

AU - Ogawa, Kaoru

AU - Inohara, Hidenori

AU - Sakamoto, Shuichi

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AU - Doi, Katsumi

AU - Tanaka, Kenji F.

AU - Hibino, Hiroshi

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