Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms

Common causes of hearing loss in humans - exposure to loud noise or ototoxic drugs and aging - often damage sensory hair cells, reflected as elevated thresholds on the clinical audiogram. Recent studies in animal models suggest, however, that well before this overt hearing loss can be seen, a more insidious, but likely more common, process is taking place that permanently interrupts synaptic communication between sensory inner hair cells and subsets of cochlear nerve fibers. The silencing of affected neurons alters auditory information processing, whether accompanied by threshold elevations or not, and is a likely contributor to a variety of perceptual abnormalities, including speech-in-noise difficulties, tinnitus and hyperacusis. Work described here will review structural and functional manifestations of this cochlear synaptopathy and will consider possible mechanisms underlying its appearance and progression in ears with and without traditional 'hearing loss' arising from several common causes in humans.

[1]  D. Šuta,et al.  Development of the acoustic startle response in rats and its change after early acoustic trauma , 2015, Behavioural Brain Research.

[2]  Leslie D. Liberman,et al.  Dynamics of cochlear synaptopathy after acoustic overexposure , 2015, Journal of the Association for Research in Otolaryngology.

[3]  M. Liberman,et al.  Age-Related Cochlear Synaptopathy: An Early-Onset Contributor to Auditory Functional Decline , 2013, The Journal of Neuroscience.

[4]  M. Liberman,et al.  Influence of Supporting Cells on Neuronal Degeneration After Hair Cell Loss , 2005, Journal of the Association for Research in Otolaryngology.

[5]  H. Dodson,et al.  Response of spiral ganglion neurones to cochlear hair cell destruction in the guinea pig , 2000, Journal of neurocytology.

[6]  H. Spoendlin Innervation densities of the cochlea. , 1972, Acta oto-laryngologica.

[7]  Anneliese Schrott-Fischer,et al.  Quantitative evaluation of myelinated nerve fibres and hair cells in cochleae of humans with age-related high-tone hearing loss , 1995, Hearing Research.

[8]  C. Berlin,et al.  N–Methyl–D–aspartate antagonists limit aminoglycoside antibiotic–induced hearing loss , 1996, Nature Medicine.

[9]  Hari M. Bharadwaj,et al.  Cochlear neuropathy and the coding of supra-threshold sound , 2014, Front. Syst. Neurosci..

[10]  S. Kujawa,et al.  Auditory sensitivity regulation via rapid changes in expression of surface AMPA receptors , 2007, Nature Neuroscience.

[11]  Paul Kruszka,et al.  Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss , 1997, International Journal of Developmental Neuroscience.

[12]  M. Liberman,et al.  Ultrastructural differences among afferent synapses on cochlear hair cells: Correlations with spontaneous discharge rate , 1996, The Journal of comparative neurology.

[13]  J. Nadol Application of electron microscopy to human otopathology. Ultrastructural findings in neural presbycusis, Menière's disease and Usher's syndrome. , 1988, Acta oto-laryngologica.

[14]  M. Liberman Single-neuron labeling in the cat auditory nerve. , 1982, Science.

[15]  B. Moore Dead Regions in the Cochlea: Conceptual Foundations, Diagnosis, and Clinical Applications , 2004, Ear and hearing.

[16]  Shi-ming Yang,et al.  Noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in mice , 2015, Acta oto-laryngologica.

[17]  Jing Wang,et al.  Neuroprotective effect of riluzole in acute noise-induced hearing loss , 2005, Neuroreport.

[18]  G. W. Harding,et al.  Degeneration in the cochlea after noise damage: primary versus secondary events. , 2000, The American journal of otology.

[19]  P. Rabinowitz,et al.  ACOEM Task Force on Occupational Hearing Loss , 2012 .

[20]  H. Schuknecht,et al.  An Experimental and Clinical Study of Deafness from Lesions of the Cochlear Nerve , 1955, The Journal of Laryngology & Otology.

[21]  H. Schuknecht,et al.  Cochlear Pathology in Presbycusis , 1993, The Annals of otology, rhinology, and laryngology.

[22]  Tobias Moser,et al.  Mechanisms underlying the temporal precision of sound coding at the inner hair cell ribbon synapse , 2006, The Journal of physiology.

[23]  M. Liberman,et al.  Auditory-nerve response from cats raised in a low-noise chamber. , 1978, The Journal of the Acoustical Society of America.

[24]  H. Spoendlin,et al.  Primary structural changes in the organ of Corti after acoustic overstimulation. , 1971, Acta oto-laryngologica.

[25]  Lijuan Shi,et al.  Silent Damage of Noise on Cochlear Afferent Innervation in Guinea Pigs and the Impact on Temporal Processing , 2012, PloS one.

[26]  G. W. Harding,et al.  Time course of nerve-fiber regeneration in the noise-damaged mammalian cochlea , 1997, International Journal of Developmental Neuroscience.

[27]  M. Liberman,et al.  Dynamics of Noise-Induced Cellular Injury and Repair in the Mouse Cochlea , 2002, Journal of the Association for Research in Otolaryngology.

[28]  Xiaowei Li,et al.  Coding Deficits in Noise-Induced Hidden Hearing Loss May Stem from Incomplete Repair of Ribbon Synapses in the Cochlea , 2016, Front. Neurosci..

[29]  Bernd Fritzsch,et al.  Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance. , 2004, Progress in brain research.

[30]  T. Yamasoba,et al.  Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application , 2008, Acta oto-laryngologica.

[31]  P. Ernfors,et al.  Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Ian M. Winter,et al.  Diversity of characteristic frequency rate-intensity functions in guinea pig auditory nerve fibres , 1990, Hearing Research.

[33]  M. Liberman,et al.  Acceleration of Age-Related Hearing Loss by Early Noise Exposure: Evidence of a Misspent Youth , 2006, The Journal of Neuroscience.

[34]  M. Liberman,et al.  Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss , 2015, Hearing Research.

[35]  N. Hakuba,et al.  Exacerbation of Noise-Induced Hearing Loss in Mice Lacking the Glutamate Transporter GLAST , 2000, The Journal of Neuroscience.

[36]  D. Furness,et al.  Comparative Distribution of Glutamate Transporters and Receptors in Relation to Afferent Innervation Density in the Mammalian Cochlea , 2003, The Journal of Neuroscience.

[37]  M. Liberman,et al.  Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss , 2009, The Journal of Neuroscience.

[38]  J. Llorens,et al.  Vestibular damage in chronic ototoxicity: a mini-review. , 2014, Neurotoxicology.

[39]  Sharon G. Kujawa,et al.  Longitudinal threshold changes in older men with audiometric notches , 2000, Hearing Research.

[40]  J. Buchwald,et al.  Far-field acoustic response: origins in the cat. , 1975, Science.

[41]  J. Puel,et al.  Excitotoxicity, Synaptic Repair, and Functional Recovery in the Mammalian Cochlea: A Review of Recent Findings , 1999, Annals of the New York Academy of Sciences.

[42]  D. Webster,et al.  Cochlear Nerve Projections following Organ of Corti Destruction , 1978, Otolaryngology.

[43]  M. Paparella,et al.  Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity , 1998, Hearing Research.

[44]  R. A. Schmiedt,et al.  Age-related loss of activity of auditory-nerve fibers. , 1996, Journal of neurophysiology.

[45]  M. Liberman,et al.  Aging after Noise Exposure: Acceleration of Cochlear Synaptopathy in “Recovered” Ears , 2015, The Journal of Neuroscience.

[46]  D. Robertson Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea , 1983, Hearing Research.

[47]  Sharon G. Kujawa,et al.  Age-Related Primary Cochlear Neuronal Degeneration in Human Temporal Bones , 2011, Journal of the Association for Research in Otolaryngology.

[48]  L. Johnsson,et al.  Sequence of Degeneration of Corti's Organ and its First-Order Neurons , 1974, The Annals of otology, rhinology, and laryngology.

[49]  Sandra Gordon-Salant,et al.  Hearing loss and aging: new research findings and clinical implications. , 2005, Journal of rehabilitation research and development.

[50]  J. Grose,et al.  Processing of Temporal Fine Structure as a Function of Age , 2010, Ear and hearing.

[51]  M. Liberman,et al.  Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates. , 2013, Journal of neurophysiology.

[52]  L. Rüttiger,et al.  Advances in the neurobiology of hearing disorders: Recent developments regarding the basis of tinnitus and hyperacusis , 2013, Progress in Neurobiology.

[53]  Barbara G Shinn-Cunningham,et al.  Normal hearing is not enough to guarantee robust encoding of suprathreshold features important in everyday communication , 2011, Proceedings of the National Academy of Sciences.

[54]  S. Lerner,et al.  Cochlear neural degeneration without hair cell loss in two patients with aminoglycoside ototoxicity. , 1987, The Journal of infectious diseases.

[55]  D. McAlpine,et al.  Tinnitus with a Normal Audiogram: Physiological Evidence for Hidden Hearing Loss and Computational Model , 2011, The Journal of Neuroscience.

[56]  M. Liberman,et al.  Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma , 2014, eLife.

[57]  R. Salvi,et al.  Reversible and irreversible damage to cochlear afferent neurons by kainic acid excitotoxicity , 2001, The Journal of comparative neurology.

[58]  M B Sachs,et al.  Nonlinearities in auditory-nerve fiber responses to bandlimited noise. , 1980, The Journal of the Acoustical Society of America.

[59]  M. Liberman,et al.  Toward a Differential Diagnosis of Hidden Hearing Loss in Humans , 2016, PloS one.

[60]  H. Boukari,et al.  XBP1 mitigates aminoglycoside-induced endoplasmic reticulum stress and neuronal cell death , 2015, Cell Death and Disease.

[61]  Bradford J. May,et al.  Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice , 2006, Hearing Research.

[62]  M. Tymianski,et al.  Calcium, ischemia and excitotoxicity. , 2010, Cell calcium.

[63]  T Kawase,et al.  Spatial organization of the auditory nerve according to spontaneous discharge rate , 1992, The Journal of comparative neurology.

[64]  John S. Oghalai,et al.  Mechanisms of Hearing Loss after Blast Injury to the Ear , 2013, PloS one.

[65]  Haobing Wang,et al.  Opposing Gradients of Ribbon Size and AMPA Receptor Expression Underlie Sensitivity Differences among Cochlear-Nerve/Hair-Cell Synapses , 2011, The Journal of Neuroscience.

[66]  Jean-Luc Puel,et al.  Contribution of auditory nerve fibers to compound action potential of the auditory nerve. , 2014, Journal of neurophysiology.

[67]  R. Salvi,et al.  Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla , 2004, Brain Research.

[68]  T. Parsons,et al.  Structure and Function of the Hair Cell Ribbon Synapse , 2006, The Journal of Membrane Biology.

[69]  Hari M. Bharadwaj,et al.  Auditory Brainstem Response Latency in Noise as a Marker of Cochlear Synaptopathy , 2016, The Journal of Neuroscience.

[70]  G. Rebillard,et al.  Physiology, pharmacology and plasticity at the inner hair cell synaptic complex , 2007, Hearing Research.

[71]  J. Puel Chemical synaptic transmission in the cochlea , 1995, Progress in Neurobiology.

[72]  Leslie D. Liberman,et al.  Olivocochlear Innervation Maintains the Normal Modiolar-Pillar and Habenular-Cuticular Gradients in Cochlear Synaptic Morphology , 2014, Journal of the Association for Research in Otolaryngology.

[73]  Noise-Induced Inner Hair Cell Ribbon Loss Disturbs Central Arc Mobilization: A Novel Molecular Paradigm for Understanding Tinnitus , 2013, Molecular Neurobiology.

[74]  Robert A Levine,et al.  Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. , 2010, Journal of neurophysiology.

[75]  E D Young,et al.  Effects of continuous noise backgrounds on rate response of auditory nerve fibers in cat. , 1984, Journal of neurophysiology.

[76]  S. Pyott,et al.  The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery , 2016, Hearing Research.

[77]  S. Amara,et al.  Excitatory amino acid transporters: a family in flux. , 1999, Annual review of pharmacology and toxicology.

[78]  R. Bridges,et al.  The excitatory amino acid transporters: pharmacological insights on substrate and inhibitor specificity of the EAAT subtypes. , 2005, Pharmacology & therapeutics.

[79]  R. Harrison,et al.  Degeneration of Spiral Ganglion Cells in the Chinchilla afterInner H air Cell Loss Induced by Carboplatin , 1998, Audiology and Neurotology.

[80]  H. Versnel,et al.  Neurotrophins and their role in the cochlea , 2012, Hearing Research.

[81]  Paul A. Fuchs,et al.  Transmitter release at the hair cell ribbon synapse , 2002, Nature Neuroscience.

[82]  P. Smith,et al.  Are vestibular hair cells excited to death by aminoglycoside antibiotics? , 2000, Journal of vestibular research : equilibrium & orientation.

[83]  J. Kaltenbach,et al.  Hyperactivity in the dorsal cochlear nucleus after intense sound exposure and its resemblance to tone-evoked activity: a physiological model for tinnitus , 2000, Hearing Research.

[84]  J. Puel,et al.  Synaptic regeneration and functional recovery after excitotoxic injury in the guinea pig cochlea. , 1995, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[85]  Lijuan Shi,et al.  Ribbon Synapse Plasticity in the Cochleae of Guinea Pigs after Noise-Induced Silent Damage , 2013, PloS one.

[86]  Q. Ruan,et al.  Topographic and quantitative evaluation of gentamicin-induced damage to peripheral innervation of mouse cochleae. , 2014, Neurotoxicology.

[87]  Mitsuru Sugawara,et al.  Survival of Adult Spiral Ganglion Neurons Requires erbB Receptor Signaling in the Inner Ear , 2004, The Journal of Neuroscience.

[88]  S. Kujawa,et al.  Regulated expression of surface AMPA receptors reduces excitotoxicity in auditory neurons. , 2009, Journal of neurophysiology.

[89]  M. Liberman,et al.  Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure , 2016, Scientific Reports.

[90]  Xiaowei Li,et al.  Coding deficits in hidden hearing loss induced by noise: the nature and impacts , 2016, Scientific Reports.

[91]  D. Hur,et al.  Secondary Apoptosis of Spiral Ganglion Cells Induced by Aminoglycoside: Fas–Fas Ligand Signaling Pathway , 2008, The Laryngoscope.

[92]  Leslie D. Liberman,et al.  Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue , 2015, Hearing Research.

[93]  N. Danbolt Glutamate uptake , 2001, Progress in Neurobiology.

[94]  Christopher J. Plack,et al.  Perceptual Consequences of “Hidden” Hearing Loss , 2014, Trends in hearing.

[95]  Chongyu Ren,et al.  Effects of Repeated “Benign” Noise Exposures in Young CBA Mice: Shedding Light on Age-related Hearing Loss , 2012, Journal of the Association for Research in Otolaryngology.

[96]  Jean-Luc Puel,et al.  Excitotoxicity and repair of cochlear synapses after noise‐trauma induced hearing loss , 1998, Neuroreport.

[97]  R. Salvi,et al.  Insensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas , 2013, Hearing Research.

[98]  M. Liberman,et al.  Is noise-induced cochlear neuropathy key to the generation of hyperacusis or tinnitus? , 2014, Journal of neurophysiology.

[99]  M. Liberman Morphological differences among radial afferent fibers in the cat cochlea: An electron-microscopic study of serial sections , 1980, Hearing Research.

[100]  T. Brozoski,et al.  Primary afferent dendrite degeneration as a cause of tinnitus , 2007, Journal of neuroscience research.

[101]  A. Thornton,et al.  Low‐Frequency Sensorineural Loss: Clinical Evaluation and Implications for Hearing Aid Fitting , 1994, Ear and hearing.

[102]  J. Eggermont,et al.  Ringing Ears: The Neuroscience of Tinnitus , 2010, The Journal of Neuroscience.

[103]  Hari M. Bharadwaj,et al.  Individual Differences Reveal Correlates of Hidden Hearing Deficits , 2015, The Journal of Neuroscience.