Engineering of functional auditory neurons from human induced pluripotent stem cells

Minjin Jeong; Lucas G. Vattino; Maja Djurisic; Kevin P. Rose; Hiroshi Hyakusoku; Svetolik Spasic; Xiao-Jie Ma; Hiroaki Mohri; Ronna Hertzano; Anne E. Takesian; Konstantina M. Stankovic

doi:10.1016/j.mmr.2026.100008

Your Location：

Home >

Browse articles >

Engineering of functional auditory neurons from human induced pluripotent stem cells

RESEARCH | Updated：2026-05-11

- Engineering of functional auditory neurons from human induced pluripotent stem cells
- Military Medical Research (2026)
- Affiliations：
  
  Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
  Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA
  Section on Omics and Translational Science of Hearing, Neurotology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
  Department of Otorhinolaryngology, Yokosuka Kyosai Hospital, Kanagawa 238-8558, Japan
  Department of Otolaryngology, Qilu Hospital of Shandong University, Jinan 250062, China
  Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94304, USA
  Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94304, USA
- Author bio：
  
  *Konstantina M. Stankovic, kstankovic@stanford.edu
- Funds：
- DOI：10.1016/j.mmr.2026.100008
  CLC：
- Received：07 July 2025，
  
  Accepted：06 March 2026，
  
  Published：2026-04
- Accepted：
Scan QR Code
Jeong M, Vattino LG, Djurisic M, Rose KP, Hyakusoku H, Spasic S, et al. Engineering of functional auditory neurons from human induced pluripotent stem cells. Mil Med Res. 2026;13(1):100008.
DOI：

Jeong M, Vattino LG, Djurisic M, Rose KP, Hyakusoku H, Spasic S, et al. Engineering of functional auditory neurons from human induced pluripotent stem cells. Mil Med Res. 2026;13(1):100008. DOI： 10.1016/j.mmr.2026.100008.

摘要

Abstract

Background:

Spiral ganglion neurons (SGNs) relay auditory sensory information from the cochlea to the brain. Their loss results in permanent hearing impairment in humans due to their limited regenerative capacity. Progress in hearing restoration has been constrained by the inaccessibility of human inner ear tissue and challenges in generating functionally mature human SGN-like neurons from stem cells

in vitro

Methods:

To generate human SGN-like neurons from human induced pluripotent stem cells (hiPSCs)

we recapitulated key signaling pathways involved in human inner ear development. On day (D) 11 of differentiation

nerve growth factor receptor-positive cells (precursors of pre-placodal ectoderm and neural crest) were isolated using magnetic sorting. From D18 to D25

cultures were treated with sonic hedgehogs to induce otic neural progenitors. Neuronal maturation was subsequently promoted by a cocktail of brain-derived neurotrophic factor

neurotrophin-3

and insulin-like growth factor-1

which supports SGN development. Cellular identity and functionality were assessed using single-cell RNA sequencing

immunocytochemistry

whole-cell patch-clamp electrophysiology

co-culture assays

and calcium ion (Ca

) imaging.

Results:

hiPSC-derived SGN-like neurons exhibited morphological

molecular

electrophysiological

and functional characteristics of SGNs

in vivo

. Neurons acquired bipolar morphology and were wrapped by glial cells. Transcriptomic analysis revealed that SGN-like neurons were distinct from other neuronal lineages and showed similarity to type I and type Ⅱ SGNs based on expression of synaptic and intrinsic excitability-related genes. Electrophysiological recordings revealed progressive hyperpolarization of resting membrane potential and emer

gence of overshooting action potentials

consistent with neuronal maturation. In co-culture systems

human SGN-like neurons formed functional synaptic connections with mouse cochlear hair cells and cochlear nucleus neurons

evidenced by Ca

transients and induction of the immediate early gene

c-Fos

Conclusions:

This study reports a robust and reproducible protocol for generating human SGN-like neurons from hiPSCs

providing a versatile platform for studying human auditory development

disease modeling

drug screening

and cell-based therapies for hearing restoration.

关键词

Keywords

references

Spoendlin H . The innervation of the organ of Corti . J Laryngol Otol . 1967 ; 81 ( 7 ): 717 - 38 .

Berglund AM , Ryugo DK . Hair cell innervation by spiral ganglion neurons in the mouse . J Comp Neurol . 1987 ; 255 ( 4 ): 560 - 70 .

Kiang NY , Watanabe T , Thomas EC , Clark LF . Stimulus coding in the cat's auditory nerve . Preliminary report. Ann Otol Rhinol Laryngol . 1962 ; 71 : 1009 - 26 .

Fekete DM , Rouiller EM , Liberman MC , Ryugo DK . The central projections of intracellularly labeled auditory nerve fibers in cats . J Comp Neurol . 1984 ; 229 ( 3 ): 432 - 50 .

Brown MC , Berglund AM , Kiang NY , Ryugo DK . Central trajectories of type Ⅱ spiral ganglion neurons . J Comp Neurol . 1988 ; 278 ( 4 ): 581 - 90 .

Schuknecht HF . Further observations on the pathology of presbycusis . Arch Otolaryngol . 1964 ; 80 : 369 - 82 .

Schuknecht HF , Gacek MR . Cochlear pathology in presbycusis . Ann Otol Rhinol Laryngol . 1993 ; 102 ( 1 Pt 2 ): 1 - 16 .

Kujawa SG , Liberman MC . Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth . J Neurosci . 2006 ; 26 ( 7 ): 2115 - 23 .

Hinojosa R , Lerner SA . Cochlear neural degeneration without hair cell loss in two patients with aminoglycoside ototoxicity . J Infect Dis . 1987 ; 156 ( 3 ): 449 - 55 .

Sagers JE , Landegger LD , Worthington S , Nadol JB , Stankovic KM . Human cochlear histopathology reflects clinical signatures of primary neural degeneration . Sci Rep . 2017 ; 7 ( 1 ): 4884 .

Brooks PM , Rose KP , MacRae ML , Rangoussis KM , Gurjar M , Hertzano R , et al . Pou3f4-expressing otic mesenchyme cells promote spiral ganglion neuron survival in the postnatal mouse cochlea . J Comp Neurol . 2020 ; 528 ( 12 ): 1967 - 85 .

Ruel J , Emery S , Nouvian R , Bersot T , Amilhon B , Van Rybroek JM , et al . Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice . Am J Hum Genet . 2008 ; 83 ( 2 ): 278 - 92 .

Johnsson LG . Sequence of degeneration of Corti's organ and its first-order neurons . Ann Otol Rhinol Laryngol . 1974 ; 83 ( 3 ): 294 - 303 .

Takeno S , Wake M , Mount RJ , Harrison RV . Degeneration of spiral ganglion cells in the chinchilla after inner hair cell loss induced by carboplatin . Audiol Neurootol . 1998 ; 3 ( 5 ): 281 - 90 .

Pauler M , Schuknecht HF , Thornton AR . Correlative studies of cochlear neuronal loss with speech discrimination and pure-tone thresholds . Arch Otorhinolaryngol . 1986 ; 243 ( 3 ): 200 - 6 .

Sone M , Schachern PA , Paparella MM . Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity . Hear Res . 1998 ; 115 ( 1-2 ): 217 - 23 .

Jr Nadol JB, . Patterns of neural degeneration in the human cochlea and auditory nerve: implications for cochlear implantation . Otolaryngol Head Neck Surg . 1997 ; 117 ( 3 Pt 1 ): 220 - 8 .

Jr Bahmad F , Merchant SN , Jr Nadol JB , Tranebjaerg L . Otopathology in Mohr-Tranebjaerg syndrome . Laryngoscope . 2007 ; 117 ( 7 ): 1202 - 8 .

Wu CC , Lin YH , Liu TC , Lin KN , Yang WS , Hsu CJ , et al . Identifying children with poor cochlear implantation outcomes using massively parallel sequencing . Medicine (Baltimore) . 2015 ; 94 ( 27 ): e1073 .

Meas SJ , Nishimura K , Scheibinger M , Dabdoub A . In vitro methods to cultivate spiral ganglion cells, and purification of cellular subtypes for induced neuronal reprogramming . Front Neurosci . 2018 ; 12 : 822 .

Kurihara S , Fujioka M , Hirabayashi M , Yoshida T , Hosoya M , Nagase M , et al . Otic organoids containing spiral ganglion neuron-like cells derived from human-induced pluripotent stem cells as a model of drug-induced neuropathy . Stem Cells Transl Med . 2022 ; 11 ( 3 ): 282 - 96 .

Matsuoka AJ , Morrissey ZD , Zhang C , Homma K , Belmadani A , Miller CA , et al . Directed differentiation of human embryonic stem cells toward placode-derived spiral ganglion-like sensory neurons . Stem Cells Trans Med . 2017 ; 6 ( 3 ): 923 - 36 .

Gunewardene N , Bergen NV , Crombie D , Needham K , Dottori M , Nayagam BA . Directing human induced pluripotent stem cells into a neurosensory lineage for auditory neuron replacement . Biores Open Access . 2014 ; 3 ( 4 ): 162 - 75 .

Nayagam BA , Edge AS , Needham K , Hyakumura T , Leung J , Nayagam DA , et al . An in vitro model of developmental synaptogenesis using cocultures of human neural progenitors and cochlear explants . Stem Cells Dev . 2013 ; 22 ( 6 ): 901 - 12 .

Needham K , Hyakumura T , Gunewardene N , Dottori M , Nayagam BA . Electrophysiological properties of neurosensory progenitors derived from human embryonic stem cells . Stem Cell Res . 2014 ; 12 ( 1 ): 241 - 9 .

Shi F , Corrales CE , Liberman MC , Edge AS . BMP4 induction of sensory neurons from human embryonic stem cells and reinnervation of sensory epithelium . Eur J Neurosci . 2007 ; 26 ( 11 ): 3016 - 23 .

Heuer RA , Nella KT , Chang HT , Coots KS , Oleksijew AM , Roque CB , et al . Three-dimensional otic neuronal progenitor spheroids derived from human embryonic stem cells . Tissue Eng Part A . 2021 ; 27 ( 3-4 ): 256 - 69 .

Boddy SL , Romero-Guevara R , Ji AR , Unger C , Corns L , Marcotti W , et al . Generation of otic lineages from integration-free human-induced pluripotent stem cells reprogrammed by mRNAs . Stem Cells Int . 2020 ; 2020 : 3692937 .

Chen W , Jongkamonwiwat N , Abbas L , Eshtan SJ , Johnson SL , Kuhn S , et al . Restoration of auditory evoked responses by human ES-cell-derived otic progenitors . Nature . 2012 ; 490 ( 7419 ): 278 - 82 .

Jeong M , Ocwieja KE , Han D , Wackym PA , Zhang Y , Brown A , et al . Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction . Commun Med . 2021 ; 1 ( 1 ): 44 .

Jacobson AG . The determination and positioning of the nose, lens and ear. II. The role of the endoderm . J Exp Zool . 1963 ; 154 : 285 - 91 .

His W . Die Häute und Höhlen des Körpers: Academisches Programm . Schweighauser ; 1865 .

Sandell LL , Butler Tjaden NE , Barlow AJ , Trainor PA . Cochleovestibular nerve development is integrated with migratory neural crest cells . Dev Biol . 2014 ; 385 ( 2 ): 200 - 10 .

Liu Z , Owen T , Zhang L , Zuo J . Dynamic expression pattern of sonic hedgehog in developing cochlear spiral ganglion neurons . Dev Dyn . 2010 ; 239 ( 6 ): 1674 - 83 .

Riccomagno MM , Martinu L , Mulheisen M , Wu DK , Epstein DJ . Specification of the mammalian cochlea is dependent on Sonic hedgehog . Genes Dev . 2002 ; 16 ( 18 ): 2365 - 78 .

Trainor PA , Tam PP . Cranial paraxial mesoderm and neural crest cells of the mouse embryo: co-distribution in the craniofacial mesenchyme but distinct segregation in branchial arches . Development . 1995 ; 121 ( 8 ): 2569 - 82 .

Freyer L , Aggarwal V , Morrow BE . Dual embryonic origin of the mammalian otic vesicle forming the inner ear . Development . 2011 ; 138 ( 24 ): 5403 - 14 .

Heuer JG , Fatemie-Nainie S , Wheeler EF , Bothwell M . Structure and developmental expression of the chicken NGF receptor . Dev Biol . 1990 ; 137 ( 2 ): 287 - 304 .

Abe H , Wataya H , Amano O , Kondo H . Localization of nerve growth factor receptor in developing inner ear of rats . Acta Otolaryngol . 1991 ; 111 ( 4 ): 691 - 8 .

Roccio M , Perny M , Ealy M , Widmer HR , Heller S , Senn P . Molecular characterization and prospective isolation of human fetal cochlear hair cell progenitors . Nat Commun . 2018 ; 9 ( 1 ): 4027 .

Szabó A , Mayor R . Mechanisms of neural crest migration . Annu Rev Genet . 2018 ; 52 : 43 - 63 .

Leung AW , Kent Morest D , Li JY . Differential BMP signaling controls formation and differentiation of multipotent preplacodal ectoderm progenitors from human embryonic stem cells . Dev Biol . 2013 ; 379 ( 2 ): 208 - 20 .

Mou K , Hunsberger CL , Cleary JM , Davis RL . Synergistic effects of BDNF and NT-3 on postnatal spiral ganglion neurons indexing terms: inner ear; cochlea; primary auditory neuron . J Comp Neurol . 1997 ; 386 : 529 - 39 .

Koundakjian EJ , Appler JL , Goodrich LV . Auditory neurons make stereotyped wiring decisions before maturation of their targets . J Neurosci . 2007 ; 27 ( 51 ): 14078 - 88 .

Hafidi A . Peripherin-like immunoreactivity in type Ⅱ spiral ganglion cell body and projections . Brain Res . 1998 ; 805 ( 1-2 ): 181 - 90 .

Spoendlin H . Degeneration behaviour of the cochlear nerve . Arch Klin Exp Ohren Nasen Kehlkopfheilkd . 1971 ; 200 ( 4 ): 275 - 91 .

Petitpré C , Faure L , Uhl P , Fontanet P , Filova I , Pavlinkova G , et al . Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification . Nat Commun . 2022 ; 13 ( 1 ): 3878 .

Sanders TR , Kelley MW . Specification of neuronal subtypes in the spiral ganglion begins prior to birth in the mouse . Proc Natl Acad Sci U S A . 2022 ; 119 ( 48 ): e2203935119 .

Locher H , Frijns JHM , van Iperen L , de Groot JCMJ , Huisman MA , Chuva de Sousa Lopes SM . Neurosensory development and cell fate determination in the human cochlea . Neural Dev . 2013 ; 8 : 20 .

Zuchero JB , Barres BA . Glia in mammalian development and disease . Development . 2015 ; 142 ( 22 ): 3805 - 9 .

Locher H , de Groot JC , van Iperen L , Huisman MA , Frijns JH , Chuva de Sousa Lopes SM . Distribution and development of peripheral glial cells in the human fetal cochlea . PLoS One . 2014 ; 9 ( 1 ): e88066 .

Rattay F , Potrusil T , Wenger C , Wise AK , Glueckert R , Schrott-Fischer A . Impact of morphometry, myelinization and synaptic current strength on spike conduction in human and cat spiral ganglion neurons . PLoS One . 2013 ; 8 ( 11 ): e79256 .

Rose KP , Manilla G , Milon B , Zalzman O , Song Y , Coate TM , et al . Spatially distinct otic mesenchyme cells show molecular and functional heterogeneity patterns before hearing onset . iScience . 2023 ; 26 ( 10 ): 107769 .

Durruthy-Durruthy R , Gottlieb A , Hartman BH , Waldhaus J , Laske RD , Altman R , et al . Reconstruction of the mouse otocyst and early neuroblast lineage at single-cell resolution . Cell . 2014 ; 157 ( 4 ): 964 - 78 .

Lu CC , Appler JM , Andres Houseman E , Goodrich LV . Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly . J Neurosci . 2011 ; 31 ( 30 ): 10903 - 18 .

Raft S , Nowotschin S , Liao J , Morrow BE . Suppression of neural fate and control of inner ear morphogenesis by Tbx1 . Development . 2004 ; 131 ( 8 ): 1801 - 12 .

Matern MS , Durruthy-Durruthy R , Birol O , Darmanis S , Scheibinger M , Groves AK , et al . Transcriptional dynamics of delaminating neuroblasts in the mouse otic vesicle . Cell Rep . 2023 ; 42 ( 6 ): 112545 .

Gleeson JG , Lin PT , Flanagan LA , Walsh CA . Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons . Neuron . 1999 ; 23 ( 2 ): 257 - 71 .

Sun Y , Wang L , Zhu T , Wu B , Wang G , Luo Z , et al . Single-cell transcriptomic landscapes of the otic neuronal lineage at multiple early embryonic ages . Cell Rep . 2022 ; 38 ( 12 ): 110542 .

Lorenzen SM , Duggan A , Osipovich AB , Magnuson MA , Garcia-Anoveros J . Insm1 promotes neurogenic proliferation in delaminated otic progenitors . Mech Dev . 2015 ; 138 Pt 3 : 233 - 45 .

Nayagam BA , Muniak MA , Ryugo DK . The spiral ganglion: connecting the peripheral and central auditory systems . Hear Res . 2011 ; 278 ( 1-2 ): 2 - 20 .

Puel JL . Chemical synaptic transmission in the cochlea . Prog Neurobiol . 1995 ; 47 ( 6 ): 449 - 76 .

Ryan AF , Schwartz IR . Preferential glutamine uptake by cochlear hair cells: implications for the afferent cochlear transmitter . Brain Res . 1984 ; 290 ( 2 ): 376 - 9 .

Niedzielski AS , Wenthold RJ . Expression of AMPA, kainate, and NMDA receptor subunits in cochlear and vestibular ganglia . J Neurosci . 1995 ; 15 ( 3 Pt 2 ): 2338 - 53 .

Rutherford MA , Bhattacharyya A , Xiao M , Cai HM , Pal I , Rubio ME . GluA3 subunits are required for appropriate assembly of AMPAR GluA2 and GluA4 subunits on cochlear afferent synapses and for presynaptic ribbon modiolar-pillar morphology . Elife . 2023 ; 12 .

Paoletti P , Bellone C , Zhou Q . NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease . Nat Rev Neurosci . 2013 ; 14 ( 6 ): 383 - 400 .

Maison SF , Casanova E , Holstein GR , Bettler B , Liberman MC . Loss of GABAB receptors in cochlear neurons: threshold elevation suggests modulation of outer hair cell function by type II afferent fibers . J Assoc Res Otolaryngol . 2009 ; 10 ( 1 ): 50 - 63 .

Conrad LJ , Grandi FC , Carlton AJ , Jeng JY , de Tomasi L , Zarecki P , et al . The upregulation of K + and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells . J Physiol . 2024 ; 602 ( 20 ): 5329 - 51 .

Shrestha BR , Chia C , Wu L , Kujawa SG , Liberman MC , Goodrich LV . Sensory neuron diversity in the inner ear is shaped by activity . Cell . 2018 ; 174 ( 5 ): 1229 - 46.e17 .

Liu W , Glueckert R , Kinnefors A , Schrott-Fischer A , Bitsche M , Rask-Andersen H . Distribution of P75 neurotrophin receptor in adult human cochlea--an immunohistochemical study . Cell Tissue Res . 2012 ; 348 ( 3 ): 407 - 15 .

Petitpré C , Wu H , Sharma A , Tokarska A , Fontanet P , Wang Y , et al . Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system . Nature Commun . 2018 ; 9 ( 1 ): 1 - 13 .

Reid MA , Flores-Otero J , Davis RL . Firing patterns of type Ⅱ spiral ganglion neurons in vitro . J Neurosci . 2004 ; 24 ( 3 ): 733 - 42 .

Crozier RA , Davis RL . Unmasking of spiral ganglion neuron firing dynamics by membrane potential and neurotrophin-3 . J Neurosci . 2014 ; 34 ( 29 ): 9688 - 702 .

Huang H , Trussell LO . KCNQ5 channels control resting properties and release probability of a synapse . Nat Neurosci . 2011 ; 14 ( 7 ): 840 - 7 .

Rudy B , McBain CJ . Kv3 channels: voltage-gated K + channels designed for high-frequency repetitive firing . Trends Neurosci . 2001 ; 24 ( 9 ): 517 - 26 .

Ottschytsch N , Raes A , Van Hoorick D , Snyders DJ . Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome . Proc Natl Acad Sci U S A . 2002 ; 99 ( 12 ): 7986 - 91 .

Markowitz AL , Kalluri R . Gradients in the biophysical properties of neonatal auditory neurons align with synaptic contact position and the intensity coding map of inner hair cells . Elife . 2020 ; 9 : e55378 .

Mo ZL , Davis RL . Heterogeneous voltage dependence of inward rectifier currents in spiral ganglion neurons . J Neurophysiol . 1997 ; 78 ( 6 ): 3019 - 27 .

Kim YH , Holt JR . Functional contributions of HCN channels in the primary auditory neurons of the mouse inner ear . J Gen Physiol . 2013 ; 142 ( 3 ): 207 - 23 .

Bando Y , Hirano T , Tagawa Y . Dysfunction of KCNK potassium channels impairs neuronal migration in the developing mouse cerebral cortex . Cereb Cortex . 2014 ; 24 ( 4 ): 1017 - 29 .

Kaczmarek LK . Modulation of potassium conductances optimizes fidelity of auditory information . Proc Natl Acad Sci U S A . 2023 ; 120 ( 12 ): e2216440120 .

Tong M , Brugeaud A , Edge AS . Regenerated synapses between postnatal hair cells and auditory neurons . J Assoc Res Otolaryngol . 2013 ; 14 ( 3 ): 321 - 9 .

Spoendlin H . The innervation of the cochlear receptor . In: Moller A , editor. Basic Mechanisms in Hearing . New York, NY : Academic Press ; 1973 . p. 185 - 234 .

Hickman TT , Hashimoto K , Liberman LD , Liberman MC . Cochlear synaptic degeneration and regeneration after noise: effects of age and neuronal subgroup . Front Cell Neurosci . 2021 ; 15 : 684706 .

Katsumi S , Sahin MI , Lewis RM , Iyer JS , Landegger LD , Stankovic KM . Intracochlear perfusion of tumor necrosis factor-alpha induces sensorineural hearing loss and synaptic degeneration in guinea pigs . Front Neurol . 2019 ; 10 : 1353 .

Zhang-Hooks Y , Agarwal A , Mishina M , Bergles DE . NMDA receptors enhance spontaneous activity and promote neuronal survival in the developing cochlea . Neuron . 2016 ; 89 ( 2 ): 337 - 50 .

De Faveri F , Ceriani F , Marcotti W . In vivo spontaneous Ca 2+ activity in the pre-hearing mammalian cochlea . Nat Commun . 2025 ; 16 ( 1 ): 29 .

Lippe WR . Rhythmic spontaneous activity in the developing avian auditory system . J Neurosci . 1994 ; 14 ( 3 Pt 2 ): 1486 - 95 .

Tritsch NX , Yi E , Gale JE , Glowatzki E , Bergles DE . The origin of spontaneous activity in the developing auditory system . Nature . 2007 ; 450 ( 7166 ): 50 - 5 .

Sonntag M , Englitz B , Kopp-Scheinpflug C , Rubsamen R . Early postnatal development of spontaneous and acoustically evoked discharge activity of principal cells of the medial nucleus of the trapezoid body: an in vivo study in mice . J Neurosci . 2009 ; 29 ( 30 ): 9510 - 20 .

Babola TA , Li S , Gribizis A , Lee BJ , Issa JB , Wang HC , et al . Homeostatic control of spontaneous activity in the developing auditory system . Neuron . 2018 ; 99 ( 3 ): 511 - 24.e5 .

Liu Q , Lee E , Davis RL . Heterogeneous intrinsic excitability of murine spiral ganglion neurons is determined by Kv1 and HCN channels . Neuroscience . 2014 ; 257 : 96 - 110 .

Xia Z , Dudek H , Miranti CK , Greenberg ME . Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism . J Neurosci . 1996 ; 16 ( 17 ): 5425 - 36 .

Vanhoutte P , Barnier JV , Guibert B , Pagès C , Besson MJ , Hipskind RA , et al . Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices . Mol Cell Biol . 1999 ; 19 ( 1 ): 136 - 46 .

Leake PA , Snyder RL . Topographic organization of the central projections of the spiral ganglion in cats . J Comp Neurol . 1989 ; 281 ( 4 ): 612 - 29 .

Pickles JO . Auditory pathways: anatomy and physiology . Handb Clin Neurol . 2015 ; 129 : 3 - 25 .

World Health Organization . Deafness and hearing loss . 2023 . Available from: https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss .

Dougherty KA . Differential developmental refinement of the intrinsic electrophysiological properties of CA1 pyramidal neurons from the rat dorsal and ventral hippocampus . Hippocampus . 2020 ; 30 ( 3 ): 233 - 49 .

Perez-García P , Pardillo-Díaz R , Geribaldi-Doldán N , Gómez-Oliva R , Domínguez-García S , Castro C , et al . Refinement of active and passive membrane properties of layer V pyramidal neurons in rat primary motor cortex during postnatal development . Front Molec Neurosci . 2021 ; 14 : 754393 .

Ruel J , Chen C , Pujol R , Bobbin RP , Puel JL . AMPA-preferring glutamate receptors in cochlear physiology of adult guinea-pig . J Physiol . 1999 ; 518 ( Pt 3 )( Pt 3 ): 667 - 80 .

Reijntjes DOJ , Pyott SJ . The afferent signaling complex: regulation of type I spiral ganglion neuron responses in the auditory periphery . Hear Res . 2016 ; 336 : 1 - 16 .

Wu JS , Vyas P , Glowatzki E , Fuchs PA . Opposing expression gradients of calcitonin-related polypeptide alpha (Calca/Cgrpα) and tyrosine hydroxylase (Th) in type Ⅱ afferent neurons of the mouse cochlea . J Comp Neurol . 2018 ; 526 ( 3 ): 425 - 38 .

Hanani M , Spray DC . Emerging importance of satellite glia in nervous system function and dysfunction . Nat Rev Neurosci . 2020 ; 21 ( 9 ): 485 - 98 .

Hosoya M , Fujioka M , Murayama AY , Okano H , Ogawa K . The common marmoset as suitable nonhuman alternative for the analysis of primate cochlear development . FEBS J . 2021 ; 288 ( 1 ): 325 - 53 .

Coate TM , Raft S , Zhao X , Ryan AK , 3rd Crenshaw EB, , Kelley MW . Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a Pou3f4/EphA4 signaling pathway . Neuron . 2012 ; 73 ( 1 ): 49 - 63 .

Whitlon DS , Grover M , Dunne SF , Richter S , Luan CH , Richter CP . Novel high content screen detects compounds that promote neurite regeneration from cochlear spiral ganglion neurons . Sci Rep . 2015 ; 5 ( 1 ): 15960 .

Bommakanti K , Iyer JS , Stankovic KM . Cochlear histopathology in human genetic hearing loss: state of the science and future prospects . Hear Res . 2019 ; 382 : 107785 .

Seyyedi M , Viana LM , Jr Nadol JB . Within-subject comparison of word recognition and spiral ganglion cell count in bilateral cochlear implant recipients . Otol Neurotol . 2014 ; 35 ( 8 ): 1446 - 50 .

Jr Nadol JB , Young YS , Glynn RJ . Survival of spiral ganglion cells in profound sensorineural hearing loss: implications for cochlear implantation . Ann Otol Rhinol Laryngol . 1989 ; 98 ( 6 ): 411 - 6 .

Orvis J , Gottfried B , Kancherla J , Adkins RS , Song Y , Dror AA , et al . gEAR: gene expression analysis resource portal for community-driven, multi-omic data exploration . Nat Methods . 2021 ; 18 ( 8 ): 843 - 4 .

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Direct current pulse elicits basilar membrane vibration in guinea pigs

Changes of the content and distribution of cochlear actin in iron-deficient growing rats

Related Author

No data

Related Institution

No data

⁰