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

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.

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

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. Wildtype and α9α10KO mice had similar ABR thresholds and acoustic startle response (ASR) amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than wildtypes in quiet and noise, but the noise:quiet amplitude ratio suggested α9α10KOs were more susceptible to masking effects for some stimuli. α9α10KO mice also had larger startle amplitudes in tone backgrounds than wildtypes. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, though 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.

Audiologic characterization using clinical physiological measures: Normative data from macaque monkeys.

Clinical auditory physiological measures (e.g., auditory brainstem responses, ABRs, and distortion product otoacoustic emissions, DPOAEs) provide diagnostic specificity for differentially diagnosing overt hearing impairments, but they remain limited in their ability to detect specific sites of lesion and subtle levels of cochlear damage. Studies in animal models may hold the key to improve differential diagnosis due to the ability to induce tightly controlled and histologically verifiable subclinical cochlear pathologies. Here, we present a normative set of traditional and clinically novel physiological measures using ABRs and DPOAEs measured in a large cohort of male macaque monkeys. Given the high similarities between macaque and human auditory anatomy, physiology, and susceptibility to hearing damage, this normative data set will serve as a crucial baseline to investigate novel physiological measures to improve diagnostics. DPOAE amplitudes were robust at f2 = 1.22, L1/L2 = 65/55, increased with frequency up to 10 kHz, and exhibited high test re-test reliability. DPOAE thresholds were lowest from 2-10 kHz and highest < 2 kHz. ABRs with a standard clinical electrode montage (vertex-to-mastoid, VM) produced Waves I-IV with a less frequently observed Wave-I, and lower thresholds. ABRs with a vertex-to-tympanic membrane (VT) electrode montage produced a more robust Wave-I, but absent Waves II-IV and higher thresholds. Further study with the VM montage revealed amplitudes that increased with stimulus level and were largest in response to click stimuli, with Wave-II showing the largest ABR amplitude, followed by -IV and -I, with high inter- and intra-subject variability. ABR wave latencies decreased with stimulus level and frequency. When stimulus presentation rate increased or stimuli were presented in close temporal proximity, ABR amplitude decreased, and latency increased. These findings expand upon existing literature of normative clinical physiological data in nonhuman primates and lay the groundwork for future studies investigating the effects of noise-induced pathologies in macaques.