Morley, B. | bioRxiv Science

bioRxiv2023

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 (9KOs) 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 (910KOs) may exhibit more severe MOC-related phenotypes. Like 9KOs, 910KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in 910KO mice. Wildtype and 910KO mice had similar ABR thresholds and acoustic startle response (ASR) amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. 910KO mice had larger ABR Wave I amplitudes than wildtypes in quiet and noise, but the noise:quiet amplitude ratio suggested 910KOs were more susceptible to masking effects for some stimuli. 910KO mice also had larger startle amplitudes in tone backgrounds than wildtypes. Overall, 910KO 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.

neuroscience↗

bioRxiv2020

Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation before hearing onset. Effects of the evolving peripheral firing pattern on spontaneous activity in the central auditory system are not well understood. Here, we describe the wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the medial olivochlear (MOC) system. Knocking out the 9/10 nicotinic acetylcholine receptor, a requisite part of the efferent cholinergic pathway, abolishes these bilateral correlations. Pharmacological and chemogenetic experiments confirm that the MOC system is necessary and sufficient to produce the bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, our results demonstrate how ascending and descending pathways collectively shape spontaneous activity patterns in the auditory system and reveal the essential role of the MOC efferent system in linking otherwise independent streams of bilateral spontaneous activity during the prehearing period.

neuroscience↗