AUTHOR=Cederholm Jennie M. E. , Parley Kristina E. , Perera Chamini J. , von Jonquieres Georg , Pinyon Jeremy L. , Julien Jean-Pierre , Ryugo David K. , Ryan Allen F. , Housley Gary D. 

TITLE=Noise-induced hearing loss vulnerability in type III intermediate filament peripherin gene knockout mice

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.962227

DOI=10.3389/fneur.2022.962227

ISSN=1664-2295

ABSTRACT=<p>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 (<italic>Prph)</italic>. Immunolabeling showed that <italic>Prph</italic> 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 <italic>Prph</italic>KO, based on suppression of distortion product otoacoustic emissions (DPOAEs) <italic>via</italic> 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 <italic>Prph</italic>KO. Auditory brainstem response (ABR) measurements demonstrated that hearing sensitivity (thresholds and growth-functions) were indistinguishable between wildtype and <italic>Prph</italic>KO 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 <italic>Prph</italic>KO mice but not the wildtype mice, consistent with the attenuated contralateral suppression of the <italic>Prph</italic>KO. These data support the postulate that auditory neurons expressing <italic>Prph</italic> contribute to the sensory arm of the otoprotective MOC feedback circuit.</p>