Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise

J Acoust Soc Am. 2024 May 1;155(5):3183-3194. doi: 10.1121/10.0025985.

Abstract

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation*
  • Animals
  • Auditory Pathways / physiology
  • Auditory Pathways / physiopathology
  • Auditory Perception / physiology
  • Auditory Threshold*
  • Behavior, Animal
  • Cochlea / physiology
  • Cochlea / physiopathology
  • Evoked Potentials, Auditory, Brain Stem*
  • Female
  • Hearing
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Noise* / adverse effects
  • Olivary Nucleus / physiology
  • Perceptual Masking
  • Phenotype
  • Receptors, Nicotinic* / deficiency
  • Receptors, Nicotinic* / genetics
  • Reflex, Startle*

Substances

  • Chrna9 protein, mouse
  • Receptors, Nicotinic
  • Chrna10 protein, mouse