Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.

Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization.

Furman AC, Kujawa SG, Liberman MC. Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates. J Neurophysiol 110: 577-586, 2013. First published April 17, 2013 doi:10.1152/jn.00164.2013.-Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4-to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortionproduct otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre-and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low-and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system. excitotoxicity; noise-induced hearing loss; auditory nerve AUDITORY NERVE (AN) fibers transmit signals from cochlear inner hair cells (IHCs) to their brainstem targets in the cochlear nucleus. Each AN fiber receives signals from a single IHC via a single ribbon synapse (Liberman 1980;Spoendlin 1969), but each hair cell is contacted by 10 -30 AN fibers depending on cochlear location and species (Bohne et al. 1982;Liberman et al. 1990;Stamataki et al. 2006). This multiple innervation is important in auditory processing, because the AN fibers contacting a single hair cell differ in spontaneous discharge rate (SR) and threshold to acoustic stimulation (Liberman 1978). The SR distribution recorded among AN fibers is fundamentally bimodal, and the low-SR (Ͻ20 sp/s) group has higher thresholds than the high-SR (Ͼ20 sp/s) group (Liberman 1978). In addition to increasing the dynamic range of the auditory periphery, the high-threshold, low-SR fibers are important for hearing in a noisy environment, by virtue of their resistance to masking by continuous background noise (Costalupes et al. 1984).Recent work in both mouse (Kujawa and Liberman 2009) and guinea pig (Lin et al. 2011) has shown that acoustic overexposures causing reversible threshold e...