The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

Douglas E. Vetter, Eleonora Katz, Stéphane F. Maison, Julia N. Taranda, Sevin Turcan, Jimena Ballestero, M. Charles Liberman, A. Bele N Elgoyhen, Jim Boulter

Research output: Contribution to journalArticle

Abstract

Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.

Original languageEnglish (US)
Pages (from-to)20594-20599
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number51
DOIs
StatePublished - Dec 18 2007
Externally publishedYes

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Nicotinic Receptors
Outer Auditory Hair Cells
Inner Auditory Hair Cells
Cholinergic Agents
Maintenance
Phenotype

Keywords

  • Cochlea
  • Electrophysiology
  • Inner hair cells
  • Outer hair cells

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system. / Vetter, Douglas E.; Katz, Eleonora; Maison, Stéphane F.; Taranda, Julia N.; Turcan, Sevin; Ballestero, Jimena; Liberman, M. Charles; Elgoyhen, A. Bele N; Boulter, Jim.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 51, 18.12.2007, p. 20594-20599.

Research output: Contribution to journalArticle

Vetter, Douglas E. ; Katz, Eleonora ; Maison, Stéphane F. ; Taranda, Julia N. ; Turcan, Sevin ; Ballestero, Jimena ; Liberman, M. Charles ; Elgoyhen, A. Bele N ; Boulter, Jim. / The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 51. pp. 20594-20599.
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abstract = "Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.",
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T1 - The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

AU - Vetter, Douglas E.

AU - Katz, Eleonora

AU - Maison, Stéphane F.

AU - Taranda, Julia N.

AU - Turcan, Sevin

AU - Ballestero, Jimena

AU - Liberman, M. Charles

AU - Elgoyhen, A. Bele N

AU - Boulter, Jim

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N2 - Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.

AB - Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice.

KW - Cochlea

KW - Electrophysiology

KW - Inner hair cells

KW - Outer hair cells

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