Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

Abstract

This study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 hours a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into 4 groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by ABR and CAP recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed one day, one week, and one month after noise exposure. After MTMI noise exposure, the amplitudes of auditory brainstem response (ABR) I and III waves were suppressed. The compound action potential (CAP) threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss, which is partially reversible after leaving the noise environment; and MTMI noise induced hidden hearing loss is associated with inner hair cell ribbon synapses.

Disruption of Glutamate Release and Uptake-Related Protein Expression After Noise-Induced Synaptopathy in the Cochlea

“…It seems that the latency of wave I was delayed after noise exposure ( Figure 2A ). Through statistical analysis, no significant difference was found in latency of wave I on day 30 (data not show), which is consistent with previous studies ( Kujawa and Liberman, 2015 ; Liberman et al, 2015 ; Fernandez et al, 2020 ; Kohrman et al, 2020 ; Wei et al, 2020 ; Song et al, 2021 ).…”

“…ABR thresholds and wave I amplitudes of Vglut3 WT animals recovered better than Vglut3 +/− mice exposed to 94 dB SPL noise, indicating that Vglut3 or glutamate release contributed to hearing recovery ( Kim et al, 2019 ). Glutamate release may also help to construct synapses ( Akil et al, 2012 ; Shi et al, 2013 ; Song et al, 2021 ). Synaptic remodeling was not observed on day 7 in the base region, and it is possible that the base region is more susceptible to noise and the development of ribbon synaptopathy.…”

“…In the inner ear, the mechanical vibration of sound wave was transformed into the electric signals by cochlear hair cells ( Wang et al, 2017 ; Liu Y. et al, 2019 ; Qi et al, 2019 , 2020 ; Zhang Y. et al, 2020 ); while spiral ganglion neurons mainly function as the neural auditory transduction cells ( Sun et al, 2016 ; Guo et al, 2019 , 2021 ; Liu W. et al, 2019b ; Zhao et al, 2019 ). Noise induced hearing loss includes damage of cochlear hair cells ( Liu et al, 2016 ; He et al, 2017 , 2021 ; Zhou et al, 2020 ; Cheng et al, 2021 ; Fu et al, 2021 ), cochlear supporting cells ( Lu et al, 2017 ; Cheng et al, 2019 ; Tan et al, 2019 ; Zhang S. et al, 2019 , 2020 ; Zhang Y. et al, 2020 ; Chen et al, 2021 ), spiral ganglion neurons ( Guo et al, 2016 , 2020 , 2021 ; Sun et al, 2016 ; Liu et al, 2021 ) and ribbon synaptopathy ( Furman et al, 2013 ; Shi et al, 2013 ; Kujawa and Liberman, 2015 ; Liberman et al, 2015 ; Bakay et al, 2018 ; Fernandez et al, 2020 ; Kohrman et al, 2020 ; Tserga et al, 2020a ; Wei et al, 2020 ; Song et al, 2021 ). It has been reported that the wave I amplitude of the auditory brainstem response (ABR) is permanently reduced and ribbon synapses between inner hair cells (IHCs) and spiral ganglion nerves are damaged after exposure to short-duration medium intensity noise ( Liberman et al, 2015 ; Fernandez et al, 2020 ; Wei et al, 2020 ).…”

Animal-to-Human Translation Difficulties and Problems With Proposed Coding-in-Noise Deficits in Noise-Induced Synaptopathy and Hidden Hearing Loss

“…Lately, however, evidence has accumulated in favor of the idea that noise-induced synaptic loss is largely or partially reversible. A recovery of synaptic counts has been found in guinea pigs ( Liu et al, 2012 ; Shi et al, 2013 ; Song et al, 2021 ), rats ( Ruttiger et al, 2013 ; Singer et al, 2013 ; Bing et al, 2015 ), and other strains of mice ( Shi et al, 2015 ; Kaur et al, 2019 ; Kim et al, 2019 ). Moreover, functional deficits in ANF units have been found to develop with recovery of the synaptic count ( Song et al, 2016 ).…”

Hidden hearing loss: current concepts

“…A decreased response to suprathreshold sounds has been linked to the loss of certain synaptic connections between the inner hair cells and the acoustic nerve in the cochlea, leading to the belief that noise-induced synaptopathy may lead to hidden hearing loss [10,11]. These synapses are located in the basal part of IHCs and consist of a presynaptic specialization known as a ‘ribbon’ that contains neurotransmitter vesicles and release apparatus, as well as a postsynaptic zone with ∝-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors [12,13 ▪▪ ]. Particularly, synapses of nerve fibres with a slow spontaneous rate, which are essential for coding sound in background noise, are severely impaired with a brief high-intensity acoustic impulses and cannot recover, which lead to the degeneration of these nerve fibres [14 ▪ ].…”