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The alpha10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system.

http://www.ncbi.nlm.nih.gov/pubmed/18077337

Although homomeric channels assembled from the alpha9 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 alpha9 and alpha10 subunits. To gain insight into alpha10 subunit function in vivo, we examined olivo cochlear innervation and function in alpha10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in alpha10(+/+) and alpha10(+/-) mice, with no detectable responses to ACh in alpha10(-/-) mice. In contrast, a proportion of alpha10(-/-) outer hair cells showed small ACh-evoked currents. In alpha10(-/-) mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual alpha9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, alpha10(-/-) 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 alpha9(-/-) and alpha10(-/-) mice have overlapping but nonidentical phenotypes. Moreover, alpha10 nAChR subunits are required for normal olivocochlear activity because alpha9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in alpha10(-/-) mutant mice.

Pubmed ID: 18077337 RIS Download

Mesh terms: Animals | Cochlea | Electric Stimulation | Electrophysiology | Hair Cells, Auditory | Mice | Mice, Knockout | Olivary Nucleus | Receptors, Nicotinic | Synapses

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Associated grants

  • Agency: NIDCD NIH HHS, Id: P30 DC 05209
  • Agency: NIDCD NIH HHS, Id: P30 DC005209
  • Agency: NIDCD NIH HHS, Id: P30 DC005209-06
  • Agency: NINDS NIH HHS, Id: P30 NS047243
  • Agency: NIDCD NIH HHS, Id: R01 DC000188
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-26
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-27
  • Agency: NIDCD NIH HHS, Id: R01 DC006258
  • Agency: NIDCD NIH HHS, Id: R01 DC0188
  • Agency: NIDCD NIH HHS, Id: R01 DC6258
  • Agency: NINDS NIH HHS, Id: R21 NS050419

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