Optogenetics reveals roles for supporting cells in force transmission to and from outer hair cells in the mouse cochlea

Victoria A Lukashkina, Snezana Levic, Patricio Simões, Zhenhang Xu, Yuju Li, Trevor Haugen, Jian Zuo, Andrei N Lukashin, Ian J Russell

Research output: Contribution to journalArticlepeer-review


Outer hair cells (OHCs) of the organ of Corti (OoC), acting as bidirectional cellular mechanoelectrical- transducers, generate, receive, and exchange forces with other major elements of the cochlear partition, including the sensory inner hair cells (IHCs). Force exchange is mediated via a supporting cell scaffold, including Deiters' (DC) and outer pillar cells (OPC), to enable the sensitivity and exquisite frequency selectivity of the mammalian cochlea and to transmit its responses to the auditory nerve. To selectively activate DCs and OPCs in male and female mice, we conditionally expressed in them a hyperpolarizing halorhodopsin (HOP), a light-gated inward chloride ion pump and measured extracellular receptor potentials (ERPs) and their DC component (ERPDCs) from the Cortilymph, which fills the OoC fluid spaces, and compared the responses with similar potentials from HOP littermates. The compound action potentials (CAP) of the auditory nerve were measured as an indication of IHC activity and transmission of cochlear responses to the CNS. HOP light-activated hyperpolarization of DCs and OPCs suppressed cochlear amplification through changing timing of its feedback, altered basilar membrane (BM) responses to tones at all measured levels and frequencies, and reduced IHC excitation. HOP-activation findings reported here complement recent studies that revealed channelrhodopsin activation depolarized DCs and OPCs and effectively bypassed, rather than blocked, the control of OHC mechanical and electrical responses to sound and their contribution to timed and directed electromechanical feedback to the mammalian cochlea. Moreover, our findings identify DCs and OPCs as potential targets for the treatment of noise-induced hearing loss. Outer hair cells provide electromechanical feedback to the organ of Corti, mediated via a cellular scaffold of Deiters' and outer pillar cells, that enables the sensitivity and fine frequency tuning of the cochlea. The role of this scaffold was explored by expressing the halorhodopsin HOP in Deiters' and pillar cells of male and female mice which became hyperpolarized when illuminated. HOP light-activated hyperpolarization suppressed cochlear amplification, altered basilar membrane responses to tones, including those at levels and frequencies not subject to amplification, and attenuated neural excitation. The findings indicate supporting cells in mediating force transmission between outer hair cells and the organ of Corti and as targets for hearing loss treatments. [Abstract copyright: Copyright © 2023 the authors.]
Original languageEnglish
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Publication statusPublished - 1 Dec 2023

Bibliographical note

Funding: UK Medical Research Council, MR/W028956/1


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