Auditory Brainstem Response to Paired Click Stimulation as an Indicator of Peripheral Synaptic Health in Noise-Induced Cochlear Synaptopathy

Abstract

IntroductionA defect in the cochlear afferent synapse between the inner hair cells and spiral ganglion neurons, after noise exposure, without changes in the hearing threshold has been reported. Animal studies on auditory evoked potentials demonstrated changes in the auditory brainstem response (ABR) measurements of peak I amplitude and the loss of synapses, which affect the temporal resolution of complex sounds. Human studies of auditory evoked potential have reported ambiguous results regarding the relationship between peak I amplitude and noise exposure. Paired click stimuli have been used to investigate the temporal processing abilities of humans and animals. In this study, we investigated the utility of measuring auditory evoked potentials in response to paired click stimuli to assess the temporal processing function of ribbon synapses in noise-induced cochlear synaptopathy.Materials and MethodsTwenty-two Sprague Dawley rats were used in this study, and synaptopathy was induced by narrow-band noise exposure (16 kHz with 1 kHz bandwidth, 105 dB sound pressure level for 2 h). ABRs to tone and paired click stimuli were measured before and 1, 3, 7, and 14 days after noise exposure. For histological analyses, hair cells and ribbon synapses were immunostained and the synapses quantified. The relationships among ABR peak I amplitude, number of synapses, and ABR to paired click stimuli were examined.ResultsOur results showed that ABR thresholds increase 1 day after noise exposure but fully recover to baseline levels after 14 days. Further, we demonstrated test frequency-dependent decreases in peak I amplitude and the number of synapses after noise exposure. These decreases were statistically significant at frequencies of 16 and 32 kHz. However, the ABR recovery threshold to paired click stimuli increased, which represent deterioration in the ability of temporal auditory processing. Our results indicate that the ABR recovery threshold is highly correlated with ABR peak I amplitude after noise exposure. We also established a direct correlation between the ABR recovery threshold and histological findings.ConclusionThe result from this study suggests that in animal studies, the ABR to paired click stimuli along with peak I amplitude has potential as an assessment tool for hidden hearing loss.

Noise-Induced Hearing Loss in Gerbil: Round Window Assays of Synapse Loss

“…The phenomenon of noise-induced and/or age-related primary cochlear neural degeneration has been documented in mice (Kujawa and Liberman, 2009 ; Sergeyenko et al, 2013 ), guinea pigs (Lin et al, 2011 ; Furman et al, 2013 ), chinchillas (Hickox et al, 2017 ; Hickman et al, 2018 ), gerbils (Gleich et al, 2016 ), rats (Lee et al, 2021 ) and rhesus macaques (Valero et al, 2017 ), as well as in humans (Wu et al, 2019 , 2021 ). However, species and even strain differences in the permanence of noise-induced losses have been reported (Shi et al, 2013 ; Wang et al, 2015 ; Kaur et al, 2019 ; Hickman et al, 2020 ).…”

Hidden hearing loss: current concepts

“…There was a permanent decline in suprathreshold responses as measured by the amplitudes of auditory brainstem response (ABR) peak I. In addition, the decrease in synapse numbers was correlated with decreasing suprathreshold responses in the basal, high-frequency areas of the cochlea [18,19]. In humans, the neural coding difficulties associated with HHL are theorized to produce deficits in speech discrimination and intelligibility, especially in noisy environments [6].…”

Active role of glia‐like supporting cells in the organ of Corti: Membrane proteins and their roles in hearing

“…Temporary threshold shifts, due to exposure to intense sound, result in a decrease in hearing sensitivity that recovers over time, whereas in permanent threshold shifts, the decrease in sensitivity does not recover to pre-exposure levels (Ryan et al, 2016). The ABR is permanently reduced when ribbon synapses between IHCs and SGNs are damaged after exposure to continuous noise (Fernandez et al, 2020;Lee et al, 2019;Lee et al, 2020;Lee et al, 2021). Noise briefly upregulates the expression of GLAST and NKAα1, which reduce glutamate or potassium toxicity in the synaptic cleft to prevent cytotoxicity (Ma et al, 2021).…”