Abstract
Recent work shows that acoustic overexposures causing only transient threshold elevation, and no hair cell loss, nevertheless can cause irreversible loss of the synapses between inner hair cells and cochlear nerve fibers (Kujawa and Liberman 2009). This cochlear synaptopathy, which is selective for the subset of sensory fibers with high thresholds and low spontaneous rates (Furman et al. 2013), appeared fully developed at 24-h post-exposure and showed no recovery by 8 weeks. However, prior studies of this synaptopathy counted only pre-synaptic ribbons, did not examine post-exposure times less than 24 h, and did not analyze the spatial patterns of degeneration around the hair cell circumference. Here, we immunostained for pre-synaptic ribbons, post-synaptic terminals and glutamate receptor patches, as well as the hair cell cytoplasm in noise-exposed and control mice to address the dynamics and spatial organization of the synaptopathic process as a function of post-exposure time from 0 h to 2 weeks. Our analysis showed that the loss of synaptic elements is nearly complete immediately after the 2-h exposure, that there is a reversible downregulation of gluR expression in the peripheral terminals which may be part of a protective mechanism, that there may be reversible reorganization of synaptic locations immediately after exposure, and that the spatial patterns are consistent with the idea that low-SR fibers are mainly found on the modiolar face of the hair cell and are the most vulnerable to noise-induced degeneration.
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Bourien J, Tang Y, Batrel C, Huet A, Lenoir M, Ladrech S, Desmadryl G, Nouvian R, Puel JL, Wang J (2014) Contribution of auditory nerve fibers to compound action potential of the auditory nerve. J Neurophysiol 112:1025–1039
Chen Z, Peppi M, Kujawa SG, Sewell WF (2009) Regulated expression of surface AMPA receptors reduces excitotoxicity in auditory neurons. J Neurophysiol 102:1152–1159
Chen Q, Mahendrasingam S, Tickle JA, Hackney CM, Furness DN, Fettiplace R (2012) The development, distribution and density of the plasma membrane calcium ATPase 2 calcium pump in rat cochlear hair cells. Eur J Neurosci 36:2302–2310
Fried MP, Dudek SE, Bohne BA (1976) Basal turn cochlear lesions following exposure to low-frequency noise. Trans Am Acad Ophthalmol Tolaryngol 82:285–298
Furman AC, Kujawa SG, Liberman MC (2013) Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates. J Neurophys 110:577–586
Kujawa SG, Liberman MC (2006) Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth. J Neurosci 26:2115–2123
Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss. J Neurosci 29:14077–14085
Kujawa SG, Micucci S, Liberman MC (2011) Noise-induced primary neural degeneration: effects of spectrum, duration, intensity and survival. In: Midwinter Meeting of the Association for Research in Otolaryngology, p 56
Liberman MC (1978) Auditory-nerve response from cats raised in a low-noise chamber. J Acoust Soc Am 63:442–455
Liberman MC (1980) Morphological differences among radial afferent fibers in the cat cochlea: an electron-microscopic study of serial sections. Hear Res 3:45–63
Liberman MC (1982) Single-neuron labeling in the cat auditory nerve. Science 216:1239–1241
Liberman MC, Kiang NY (1978) Acoustic trauma in cats. Cochlear pathology and auditory-nerve activity. Acta Otolaryngol 358:1–63
Liberman MC, Mulroy MJ (1982) Acute and chronic effects of acoustic trauma: cochlear pathology and auditory nerve pathophysiology. In: New perspectives on noise-induced hearing loss (Hamernik RP, Henderson D, Salvi R, eds), pp 105–136.
Liberman MC, Dodds LW, Pierce S (1990) Afferent and efferent innervation of the cat cochlea: quantitative analysis with light and electron microscopy. J Comp Neurol 301:443–460
Liberman LD, Wang H, Liberman MC (2011) Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve/hair-cell synapses. J Neurosci : Off J Soc Neurosci 31:801–808
Lobarinas E, Salvi R, Ding D (2013) Insensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas. Hear Res 302:113–120
Matsubara A, Laake JH, Davanger S, Usami S, Ottersen OP (1996) Organization of AMPA receptor subunits at a glutamate synapse: a quantitative immunogold analysis of hair cell synapses in the rat organ of Corti. J Neurosci : Off J Soc Neurosci 16:4457–4467
McLean WJ, Smith KA, Glowatzki E, Pyott SJ (2009) Distribution of the Na, K-ATPase alpha subunit in the rat spiral ganglion and organ of corti. J Assoc Res Otolaryngol 10:37–49
Muller M, von Hunerbein K, Hoidis S, Smolders JW (2005) A physiological place-frequency map of the cochlea in the CBA/J mouse. Hear Res 202:63–73
Narayan SS, Ruggero MA (2000) Basilar membrane mechanics at the hook region of the chinchilla cochlea. In: Recent developments in auditory mechanics (Wada H, Takasaka T, Ikeda K, Ohyama K, Koike T, eds), pp 95–101: World Scientific Press.
Robertson D (1983) Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea. Hear Res 9:263–278
Schmiedt RA, Schulte BA (1992) Physiologic and histopathologic changes in quiet- and noise-aged gerbil cochleas. In: Dancer AL, Henderson D, Salvi RJ, Hamernik RP (eds) Noise induced hearing loss. Mosby, St. Louis, pp 246–258
Schuknecht HF, Woellner RC (1955) An experimental and clinical study of deafness from lesions of the cochlear nerve. J Laryngology Otology 69:75–97
Sergeyenko Y, Lall K, Liberman MC, Kujawa SG (2013) Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline. J Neurosci : Off J Soc Neurosci 33:13686–13694
Sheets L, Kindt KS, Nicolson T (2012) Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells. J Neurosci 32:17273–17286
Spoendlin H (1971) Primary structural changes in the organ of Corti after acoustic overstimulation. Acta Otolaryngol 71:166–176
Stamataki S, Francis HW, Lehar M, May BJ, Ryugo DK (2006) Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice. Hear Res 221:104–118
Wang Y, Hirose K, Liberman MC (2002) Dynamics of noise-induced cellular injury and repair in the mouse cochlea. J Assoc Res Otolaryngol 3:248–268
Yin Y, Liberman LD, Maison SF, Liberman MC (2014) Olivocochlear innervation maintains the normal modiolar-pillar and habenular-cuticular gradients in cochlear synaptic morphology. J Assoc Res Otolaryngol 15:571–583
Yoshida N, Hequembourg SJ, Atencio CA, Rosowski JJ, Liberman MC (2000) Acoustic injury in mice: 129/SvEv is exceptionally resistant to noise-induced hearing loss. Hear Res 141:97–106
Yuan Y, Shi F, Yin Y, Tong M, Lang H, Polley DB, Liberman MC, Edge AS (2014) Ouabain-induced cochlear nerve degeneration: synaptic loss and plasticity in a mouse model of auditory neuropathy. J Assoc Res Otolaryngol 15:31–43
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This research was supported by grants from the NIDCD: R01 DC 0188 and P30 DC 05209.
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Appendix 1
F and p values from the ANOVA analyses used to assess statistical significance. Only those pairwise comparisons found to be significant at the p < 0.01 level, as indicated by asterisks in the Figures, are listed here (GIF 184 kb)
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Liberman, L.D., Liberman, M.C. Dynamics of cochlear synaptopathy after acoustic overexposure. JARO 16, 205–219 (2015). https://doi.org/10.1007/s10162-015-0510-3
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DOI: https://doi.org/10.1007/s10162-015-0510-3