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Published in: Journal of the Association for Research in Otolaryngology 1/2014

01-02-2014 | Research Article

Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy

Authors: Yasheng Yuan, Fuxin Shi, Yanbo Yin, Mingjie Tong, Hainan Lang, Daniel B. Polley, M. Charles Liberman, Albert S.B. Edge

Published in: Journal of the Association for Research in Otolaryngology | Issue 1/2014

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Abstract

Ouabain application to the round window can selectively destroy type-I spiral ganglion cells, producing an animal model of auditory neuropathy. To assess the long-term effects of this deafferentation on synaptic organization in the organ of Corti and cochlear nucleus, and to ask whether surviving cochlear neurons show any post-injury plasticity in the adult, we quantified the peripheral and central synapses of type-I neurons at posttreatment times ranging from 1 to 3 months. Measures of normal DPOAEs and greatly reduced auditory brainstem responses (ABRs) confirmed the neuropathy phenotype. Counts of presynaptic ribbons and postsynaptic glutamate receptor patches in the inner hair cell area decreased with post-exposure time, as did counts of cochlear nerve terminals in the cochlear nucleus. Although these counts provided no evidence of new synapse formation via branching from surviving neurons, the regular appearance of ectopic neurons in the inner hair cell area suggested that neurite extension is not uncommon. Correlations between pathophysiology and histopathology showed that ABR thresholds are very insensitive to even massive neural degeneration, whereas the amplitude of ABR wave 1 is a better metric of synaptic degeneration.
Literature
go back to reference Azarias G, Kruusmagi M, Connor S, Akkuratov EE, Liu XL, Lyons D, Brismar H, Broberger C, Aperia A (2012) A specific and essential role for Na,K-ATPase alpha3 in neurons co-expressing alpha1 and alpha3. J Biol Chem. Azarias G, Kruusmagi M, Connor S, Akkuratov EE, Liu XL, Lyons D, Brismar H, Broberger C, Aperia A (2012) A specific and essential role for Na,K-ATPase alpha3 in neurons co-expressing alpha1 and alpha3. J Biol Chem.
go back to reference Brown MC (1994) Antidromic responses of single units from the spiral ganglion. J Neurophysiol 71:1835–1847PubMed Brown MC (1994) Antidromic responses of single units from the spiral ganglion. J Neurophysiol 71:1835–1847PubMed
go back to reference Buran BN, Strenzke N, Neef A, Gundelfinger ED, Moser T, Liberman MC (2010) Onset coding is degraded in auditory nerve fibers from mutant mice lacking synaptic ribbons. J Neurosci 30:7587–7597PubMedCentralPubMedCrossRef Buran BN, Strenzke N, Neef A, Gundelfinger ED, Moser T, Liberman MC (2010) Onset coding is degraded in auditory nerve fibers from mutant mice lacking synaptic ribbons. J Neurosci 30:7587–7597PubMedCentralPubMedCrossRef
go back to reference Chen W, Jongkamonwiwat N, Abbas L, Eshtan SJ, Johnson SL, Kuhn S, Milo M, Thurlow JK, Andrews PW, Marcotti W, Moore HD, Rivolta MN (2012) Restoration of auditory-evoked responses by human ES-cell-derived otic progenitors. Nature 490:278–282PubMedCentralPubMedCrossRef Chen W, Jongkamonwiwat N, Abbas L, Eshtan SJ, Johnson SL, Kuhn S, Milo M, Thurlow JK, Andrews PW, Marcotti W, Moore HD, Rivolta MN (2012) Restoration of auditory-evoked responses by human ES-cell-derived otic progenitors. Nature 490:278–282PubMedCentralPubMedCrossRef
go back to reference Corrales CE, Pan L, Li H, Liberman MC, Heller S, Edge AS (2006) Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: growth of processes into the organ of Corti. J Neurobiol 66:1489–1500PubMedCentralPubMedCrossRef Corrales CE, Pan L, Li H, Liberman MC, Heller S, Edge AS (2006) Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: growth of processes into the organ of Corti. J Neurobiol 66:1489–1500PubMedCentralPubMedCrossRef
go back to reference Durrant JD, Wang J, Ding DL, Salvi RJ (1998) Are inner or outer hair cells the source of summating potentials recorded from the round window? J Acoust Soc Am 104:370–377PubMedCrossRef Durrant JD, Wang J, Ding DL, Salvi RJ (1998) Are inner or outer hair cells the source of summating potentials recorded from the round window? J Acoust Soc Am 104:370–377PubMedCrossRef
go back to reference Frank T, Rutherford MA, Strenzke N, Neef A, Pangrsic T, Khimich D, Fejtova A, Gundelfinger ED, Liberman MC, Harke B, Bryan KE, Lee A, Egner A, Riedel D, Moser T (2010) Bassoon and the synaptic ribbon organize Ca(2) + channels and vesicles to add release sites and promote refilling. Neuron 68:724–738PubMedCentralPubMedCrossRef Frank T, Rutherford MA, Strenzke N, Neef A, Pangrsic T, Khimich D, Fejtova A, Gundelfinger ED, Liberman MC, Harke B, Bryan KE, Lee A, Egner A, Riedel D, Moser T (2010) Bassoon and the synaptic ribbon organize Ca(2) + channels and vesicles to add release sites and promote refilling. Neuron 68:724–738PubMedCentralPubMedCrossRef
go back to reference Khimich D, Nouvian R, Pujol R, Tom Dieck S, Egner A, Gundelfinger ED, Moser T (2005) Hair cell synaptic ribbons are essential for synchronous auditory signaling. Nature 434:889–894PubMedCrossRef Khimich D, Nouvian R, Pujol R, Tom Dieck S, Egner A, Gundelfinger ED, Moser T (2005) Hair cell synaptic ribbons are essential for synchronous auditory signaling. Nature 434:889–894PubMedCrossRef
go back to reference Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss. J Neurosci 29:14077–14085PubMedCentralPubMedCrossRef Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss. J Neurosci 29:14077–14085PubMedCentralPubMedCrossRef
go back to reference Lang H, Schulte BA, Schmiedt RA (2005) Ouabain induces apoptotic cell death in type I spiral ganglion neurons, but not type II neurons. J Assoc Res Otolaryngol 6:63–74PubMedCentralPubMedCrossRef Lang H, Schulte BA, Schmiedt RA (2005) Ouabain induces apoptotic cell death in type I spiral ganglion neurons, but not type II neurons. J Assoc Res Otolaryngol 6:63–74PubMedCentralPubMedCrossRef
go back to reference Lang H, Schulte BA, Goddard JC, Hedrick M, Schulte JB, Wei L, Schmiedt RA (2008) Transplantation of mouse embryonic stem cells into the cochlea of an auditory-neuropathy animal model: effects of timing after injury. J Assoc Res Otolaryngol 9:225–240PubMedCentralPubMedCrossRef Lang H, Schulte BA, Goddard JC, Hedrick M, Schulte JB, Wei L, Schmiedt RA (2008) Transplantation of mouse embryonic stem cells into the cochlea of an auditory-neuropathy animal model: effects of timing after injury. J Assoc Res Otolaryngol 9:225–240PubMedCentralPubMedCrossRef
go back to reference Lang H, Li M, Kilpatrick LA, Zhu J, Samuvel DJ, Krug EL, Goddard JC (2011) Sox2 upregulation and glial cell proliferation following degeneration of spiral ganglion neurons in the adult mouse inner ear. J Assoc Res Otolaryngol 12:151–171PubMedCentralPubMedCrossRef Lang H, Li M, Kilpatrick LA, Zhu J, Samuvel DJ, Krug EL, Goddard JC (2011) Sox2 upregulation and glial cell proliferation following degeneration of spiral ganglion neurons in the adult mouse inner ear. J Assoc Res Otolaryngol 12:151–171PubMedCentralPubMedCrossRef
go back to reference Lawner BE, Harding GW, Bohne BA (1997) Time course of nerve-fiber regeneration in the noise-damaged mammalian cochlea. Int J Dev Neurosci 15:601–617PubMedCrossRef Lawner BE, Harding GW, Bohne BA (1997) Time course of nerve-fiber regeneration in the noise-damaged mammalian cochlea. Int J Dev Neurosci 15:601–617PubMedCrossRef
go back to reference Liberman MC, Chesney CP, Kujawa SG (1997) Effects of selective inner hair cell loss on DPOAE and CAP in carboplatin-treated chinchillas. Audit Neurosci 3:255–268 Liberman MC, Chesney CP, Kujawa SG (1997) Effects of selective inner hair cell loss on DPOAE and CAP in carboplatin-treated chinchillas. Audit Neurosci 3:255–268
go back to reference 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 31:801–808PubMedCentralPubMedCrossRef 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 31:801–808PubMedCentralPubMedCrossRef
go back to reference Lin HW, Furman AC, Kujawa SG, Liberman MC (2011) Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift. J Assoc Res Otolaryngol 12:605–616PubMedCentralPubMedCrossRef Lin HW, Furman AC, Kujawa SG, Liberman MC (2011) Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift. J Assoc Res Otolaryngol 12:605–616PubMedCentralPubMedCrossRef
go back to reference 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 16:4457–4467PubMed 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 16:4457–4467PubMed
go back to reference 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 10:37–49PubMedCentralPubMedCrossRef 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 10:37–49PubMedCentralPubMedCrossRef
go back to reference Meyer AC, Frank T, Khimich D, Hoch G, Riedel D, Chapochnikov NM, Yarin YM, Harke B, Hell SW, Egner A, Moser T (2009) Tuning of synapse number, structure, and function in the cochlea. Nat Neurosci 12:444–453PubMedCrossRef Meyer AC, Frank T, Khimich D, Hoch G, Riedel D, Chapochnikov NM, Yarin YM, Harke B, Hell SW, Egner A, Moser T (2009) Tuning of synapse number, structure, and function in the cochlea. Nat Neurosci 12:444–453PubMedCrossRef
go back to reference Mulders WH, Robertson D (2009) Hyperactivity in the auditory midbrain after acoustic trauma: dependence on cochlear activity. Neuroscience 164:733–746PubMedCrossRef Mulders WH, Robertson D (2009) Hyperactivity in the auditory midbrain after acoustic trauma: dependence on cochlear activity. Neuroscience 164:733–746PubMedCrossRef
go back to reference 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 202:63–73PubMedCrossRef 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 202:63–73PubMedCrossRef
go back to reference Opazo P, Sainlos M, Choquet D (2012) Regulation of AMPA receptor surface diffusion by PSD-95 slots. Curr Opin Neurobiol 22:453–460PubMedCrossRef Opazo P, Sainlos M, Choquet D (2012) Regulation of AMPA receptor surface diffusion by PSD-95 slots. Curr Opin Neurobiol 22:453–460PubMedCrossRef
go back to reference Pangrsic T, Lasarow L, Reuter K, Takago H, Schwander M, Riedel D, Frank T, Tarantino LM, Bailey JS, Strenzke N, Brose N, Muller U, Reisinger E, Moser T (2010) Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells. Nat Neurosci 13:869–876PubMedCrossRef Pangrsic T, Lasarow L, Reuter K, Takago H, Schwander M, Riedel D, Frank T, Tarantino LM, Bailey JS, Strenzke N, Brose N, Muller U, Reisinger E, Moser T (2010) Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells. Nat Neurosci 13:869–876PubMedCrossRef
go back to reference Pujol R, Puel JL (1999) Excitotoxicity, synaptic repair, and functional recovery in the mammalian cochlea: a review of recent findings. Ann N Y Acad Sci 884:249–254PubMedCrossRef Pujol R, Puel JL (1999) Excitotoxicity, synaptic repair, and functional recovery in the mammalian cochlea: a review of recent findings. Ann N Y Acad Sci 884:249–254PubMedCrossRef
go back to reference Pujol R, Lenoir M, Robertson D, Eybalin M, Johnstone BM (1985) Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells. Hear Res 18:145–151PubMedCrossRef Pujol R, Lenoir M, Robertson D, Eybalin M, Johnstone BM (1985) Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells. Hear Res 18:145–151PubMedCrossRef
go back to reference Santarelli R, Del Castillo I, Rodriguez-Ballesteros M, Scimemi P, Cama E, Arslan E, Starr A (2009) Abnormal cochlear potentials from deaf patients with mutations in the otoferlin gene. J Assoc Res Otolaryngol 10:545–556PubMedCentralPubMedCrossRef Santarelli R, Del Castillo I, Rodriguez-Ballesteros M, Scimemi P, Cama E, Arslan E, Starr A (2009) Abnormal cochlear potentials from deaf patients with mutations in the otoferlin gene. J Assoc Res Otolaryngol 10:545–556PubMedCentralPubMedCrossRef
go back to reference Schmiedt RA, Okamura HO, Lang H, Schulte BA (2002) Ouabain application to the round window of the gerbil cochlea: a model of auditory neuropathy and apoptosis. J Assoc Res Otolaryngol 3:223–233PubMedCrossRef Schmiedt RA, Okamura HO, Lang H, Schulte BA (2002) Ouabain application to the round window of the gerbil cochlea: a model of auditory neuropathy and apoptosis. J Assoc Res Otolaryngol 3:223–233PubMedCrossRef
go back to reference 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 221:104–118PubMedCrossRef 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 221:104–118PubMedCrossRef
go back to reference Stankovic K, Rio C, Xia A, Sugawara M, Adams JC, Liberman MC, Corfas G (2004) Survival of adult spiral ganglion neurons requires erbB receptor signaling in the inner ear. J Neurosci 24:8651–8661PubMedCrossRef Stankovic K, Rio C, Xia A, Sugawara M, Adams JC, Liberman MC, Corfas G (2004) Survival of adult spiral ganglion neurons requires erbB receptor signaling in the inner ear. J Neurosci 24:8651–8661PubMedCrossRef
go back to reference Starr A, Picton TW, Sininger Y, Hood LJ, Berlin CI (1996) Auditory neuropathy. Brain 119(Pt 3):741–753PubMedCrossRef Starr A, Picton TW, Sininger Y, Hood LJ, Berlin CI (1996) Auditory neuropathy. Brain 119(Pt 3):741–753PubMedCrossRef
go back to reference Taberner AM, Liberman MC (2005) Response properties of single auditory nerve fibers in the mouse. J Neurophysiol 93:557–569PubMedCrossRef Taberner AM, Liberman MC (2005) Response properties of single auditory nerve fibers in the mouse. J Neurophysiol 93:557–569PubMedCrossRef
go back to reference Vogler DP, Robertson D, Mulders WH (2011) Hyperactivity in the ventral cochlear nucleus after cochlear trauma. J Neurosci 31:6639–6645PubMedCrossRef Vogler DP, Robertson D, Mulders WH (2011) Hyperactivity in the ventral cochlear nucleus after cochlear trauma. J Neurosci 31:6639–6645PubMedCrossRef
go back to reference Wang Q, Green SH (2011) Functional role of neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro. J Neurosci 31:7938–7949PubMedCentralPubMedCrossRef Wang Q, Green SH (2011) Functional role of neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro. J Neurosci 31:7938–7949PubMedCentralPubMedCrossRef
go back to reference Zhou J, Nannapaneni N, Shore S (2007) Vesicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus. J Comp Neurol 500:777–787PubMedCrossRef Zhou J, Nannapaneni N, Shore S (2007) Vesicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus. J Comp Neurol 500:777–787PubMedCrossRef
Metadata
Title
Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy
Authors
Yasheng Yuan
Fuxin Shi
Yanbo Yin
Mingjie Tong
Hainan Lang
Daniel B. Polley
M. Charles Liberman
Albert S.B. Edge
Publication date
01-02-2014
Publisher
Springer US
Published in
Journal of the Association for Research in Otolaryngology / Issue 1/2014
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI
https://doi.org/10.1007/s10162-013-0419-7

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