Noise-induced cochlear synaptopathy in rhesus monkeys ( Macaca mulatta )

Abstract

Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 hrs. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12-27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50-75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents.

Supra-threshold psychoacoustics and envelope-following response relations: normal-hearing, synaptopathy and cochlear gain loss

“…The role of cochlear synaptopathy (i.e., the loss of inner-hair-cell auditory-nerve fiber synapses due to noise exposure or aging; or hidden hearing loss) for supra-threshold hearing has been heavily contested in recent human studies [1, 2, 3, 4] even though animal studies show clear histological evidence for synaptopathy [5, 6, 7]. It is not clear whether the cause of the missing correlations between subcortical EEG measures, as a non-invasive tool to quantify synaptopathy, and the suprathreshold psychoacoustic tasks stems from methodological confounds.…”

The Derived-Band Envelope Following Response and its Sensitivity to Sensorineural Hearing Deficits

“…The original model implementation introduced the same number of synapses between inner-hair-cells (IHCs) and AN fibers for all simulated characteristic frequencies (CF), whereas human and rhesus monkey innervation patterns show a bell-shaped pattern across CF. To make the model more realistic, the averaged synaptic counts of four control rhesus monkeys (seven ears) and nine frequencies (Valero et al, 2017) were mapped to corresponding fractional distances of the human cochlea using the monkey place-frequency map (Greenwood, 1990). Fractional distances from the base of cochlea, d i , were calculated according to the measured frequency points : The obtained d i s were substituted into the analogous Greenwood map equation for humans, yielding the corresponding frequency points : To calibrate the model with the applied AN pattern, a 70 dB-nHL click-train containing both stimulus polarities was presented at a rate of 11 Hz.…”

“…Recent animal studies have shown that overexposure to noise, ageing and ototoxicity can lead to an irreversible loss of AN synapses, i.e. cochlear synaptopathy (CS), and delayed degeneration of cochlear neurons, while leaving the cochlear sensory hair cells intact (Kujawa and Liberman, 2009; Lin et al, 2011; Liu et al, 2012; Furman et al, 2013; Lobarinas et al, 2017; Valero et al, 2017). Even if the noise exposure dose only causes a temporary threshold shift (Kujawa and Liberman, 2009), noise-induced AN fibers degeneration can progress through the lifespan and yield an increased sensitivity of the ear to age-induced hearing dysfunction (Fernandez et al, 2015).…”

Neural signatures of disordered multi-talker speech perception in adults with normal hearing

“…The mechanism for poor encoding of sTFS cues remains to be determined, though one possibility is that 36 it reflects a loss of cochlear afferent neurons that synapse onto inner hair cells. Auditory nerve fiber loss 37 has been observed in cochlear regions with normal thresholds in many animal species as well as post-38 mortem analysis of human temporal bone specimens (Wu et al, 2018;Valero et al, 2017;Viana et al, 39 2015;Furman, Kujawa and Liberman, 2013;Kujawa and Liberman, 2009). In humans, recent findings 40 suggest that appreciable auditory nerve fiber loss begins in early adulthood, well before degeneration is 41 noted in cochlear sensory cells or spiral ganglion cell bodies (Wu et al, 2018).…”