Amplification mode differs along the length of the mouse cochlea as revealed by connexin 26 deletion from specific gap junctions

Victoria A Lukashkina,Andrei N Lukashkin,Jian Zuo,Ian J Russell,Tetsuji Yamashita

doi:10.1038/s41598-017-04279-3

Victoria A Lukashkina, Andrei N Lukashkin + Show 3 more

Open Access

https://doi.org/10.1038/s41598-017-04279-3

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Abstract

The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters’ cells (DCs) and pillar cells (PCs), coupled by gap-junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving-voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses. However, the Cx26 cKO desensitizes mid-high-frequency DPOAEs and active BM responses and sensitizes low-mid-frequency neural excitation. This functional segregation may indicate that the flexible, apical turn cochlear partition facilitates transfer of OHC displacements (isotonic forces) for cochlear amplification and neural excitation. DC and PC Cx26 expression is essential for cochlear amplification in the stiff basal turn, possibly through maintaining cochlear partition mechanical impedance, thereby ensuring effective transfer of OHC isometric forces.

Highlights

Mechanical impedance matching in the mammalian cochlea[1, 2] enables the transfer of voltage-dependent, prestin-driven forces[3], between the outer hair cells (OHCs) and structures of the cochlear partition
Based on measurements of DPOAE audiograms, which provide a direct indicator of cochlear sensitivity at the level of the OHCs, there is no significant difference in cochlear sensitivity between connexin 26 (Cx26) conditional knockout (cKO) mice and their wild type littermates for f2 frequencies between 2 kHz, which is close to the low frequency range of cochlear mediated hearing in mice[30, 31], and ~25 kHz at stimulus (f2) levels of 50 dB sound pressure levels (SPLs) and below
Loss of expression of Cx26 in Deiters’ cells (DCs) and pillar cells (PCs) has no consequences for excitation and amplification of OHCs for frequencies below 25 kHz in the Cx26 cKO mouse cochlea, but it has profound consequences for cochlear amplification above this frequency place

Summary

Introduction

Mechanical impedance matching in the mammalian cochlea[1, 2] enables the transfer of voltage-dependent, prestin-driven forces[3], between the OHCs and structures of the cochlear partition. The impression gained, from mechanical measurements and the functional organisation of the cochlea is that OHC voltage dependent forces in the apex of the cochlea are translated into displacements or isotonic forces, while those in the high-frequency base are translated into stiffness changes or isometric forces[6]. This nonlinear frequency-dependent force, which boosts the sensitivity of cochlear responses to low-level sounds and compresses them at high levels, is known as the cochlear amplifier[12]. Deletion seriously impairs cochlear amplification in the basal high frequency region of the cochlea, but may augment amplification in the apical region of the cochlea and signal transfer from the sensory-motor OHCs to the sensory inner hair cells (IHCs)

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