TY - JOUR
T1 - Noise-induced hearing loss vulnerability in type III intermediate filament peripherin gene knockout mice
AU - Cederholm, Jennie M.E.
AU - Parley, Kristina E.
AU - Perera, Chamini J.
AU - von Jonquieres, Georg
AU - Pinyon, Jeremy L.
AU - Julien, Jean Pierre
AU - Ryugo, David K.
AU - Ryan, Allen F.
AU - Housley, Gary D.
N1 - Funding Information:
This work was supported by Australia grants from the National Health & Medical Research Council (NHMRC) APP1052463, APP1189113, and APP1188643 & U.S. Department of Veterans Affairs grants BX001205 and RX002704. The authors declare that this study also received funding from Alan and Lynne Rydge to the Hearing Research Lab at the Garvan Institute. They were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Publisher Copyright:
Copyright © 2022 Cederholm, Parley, Perera, von Jonquieres, Pinyon, Julien, Ryugo, Ryan and Housley.
PY - 2022/9/26
Y1 - 2022/9/26
N2 - In the post-natal mouse cochlea, type II spiral ganglion neurons (SGNs) innervating the electromotile outer hair cells (OHCs) of the ‘cochlear amplifier' selectively express the type III intermediate filament peripherin gene (Prph). Immunolabeling showed that Prph knockout (KO) mice exhibited disruption of this (outer spiral bundle) afferent innervation, while the radial fiber (type I SGN) innervation of the inner hair cells (~95% of the SGN population) was retained. Functionality of the medial olivocochlear (MOC) efferent innervation of the OHCs was confirmed in the PrphKO, based on suppression of distortion product otoacoustic emissions (DPOAEs) via direct electrical stimulation. However, “contralateral suppression” of the MOC reflex neural circuit, evident as a rapid reduction in cubic DPOAE when noise is presented to the opposite ear in wildtype mice, was substantially disrupted in the PrphKO. Auditory brainstem response (ABR) measurements demonstrated that hearing sensitivity (thresholds and growth-functions) were indistinguishable between wildtype and PrphKO mice. Despite this comparability in sound transduction and strength of the afferent signal to the central auditory pathways, high-intensity, broadband noise exposure (108 dB SPL, 1 h) produced permanent high frequency hearing loss (24–32 kHz) in PrphKO mice but not the wildtype mice, consistent with the attenuated contralateral suppression of the PrphKO. These data support the postulate that auditory neurons expressing Prph contribute to the sensory arm of the otoprotective MOC feedback circuit.
AB - In the post-natal mouse cochlea, type II spiral ganglion neurons (SGNs) innervating the electromotile outer hair cells (OHCs) of the ‘cochlear amplifier' selectively express the type III intermediate filament peripherin gene (Prph). Immunolabeling showed that Prph knockout (KO) mice exhibited disruption of this (outer spiral bundle) afferent innervation, while the radial fiber (type I SGN) innervation of the inner hair cells (~95% of the SGN population) was retained. Functionality of the medial olivocochlear (MOC) efferent innervation of the OHCs was confirmed in the PrphKO, based on suppression of distortion product otoacoustic emissions (DPOAEs) via direct electrical stimulation. However, “contralateral suppression” of the MOC reflex neural circuit, evident as a rapid reduction in cubic DPOAE when noise is presented to the opposite ear in wildtype mice, was substantially disrupted in the PrphKO. Auditory brainstem response (ABR) measurements demonstrated that hearing sensitivity (thresholds and growth-functions) were indistinguishable between wildtype and PrphKO mice. Despite this comparability in sound transduction and strength of the afferent signal to the central auditory pathways, high-intensity, broadband noise exposure (108 dB SPL, 1 h) produced permanent high frequency hearing loss (24–32 kHz) in PrphKO mice but not the wildtype mice, consistent with the attenuated contralateral suppression of the PrphKO. These data support the postulate that auditory neurons expressing Prph contribute to the sensory arm of the otoprotective MOC feedback circuit.
KW - cochlea
KW - contralateral suppression
KW - distortion product otoacoustic emission (DPOAE)
KW - medial olivocochlear (MOC) efferents
KW - type II spiral ganglion neurons
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U2 - 10.3389/fneur.2022.962227
DO - 10.3389/fneur.2022.962227
M3 - Article
C2 - 36226085
AN - SCOPUS:85139484935
SN - 1664-2295
VL - 13
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 962227
ER -