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

Abstract

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.

Role of the Intermediate Filament Protein Peripherin in Health and Disease

“…Peripherin is expressed in both type I and type II SGNs during development, but its expression becomes restricted to type II SGNs shortly after birth [ 66 ]. In peripherin knock-out mice, the type II SGNs were disrupted and the OHCs lost their innervation, causing a greater vulnerability to acoustic overstimulation [ 67 ]. The reduced synaptic transmission of the type II SGNs, after unilateral cochlear ablation, resulted in decreased peripherin mRNA in the inferior colliculus [ 68 ].…”

Damage-evoked signals in cochlear neurons and supporting cells

“…Previous work has examined the hypothesis that type II cochlear afferents may be not only acoustic sensors (1)(2)(3), but additionally respond to tissue damage as potential inner ear nociceptors (4)(5)(6). Their role in activation of the medial olivocochlear (MOC) neurons remains to be delineated fully (7)(8)(9), although type II afferents are unlikely to provide the dynamic range and frequency selectivity of the MOC efferents (10,11). Of equal importance, it is known that local damage in cochlear explants can trigger intercellular calcium signals that propagate through surrounding epithelia (12,13).…”