Preserved Vestibular Function in Mice with Loss of α-9 Subunit of the α-9/10 Nicotinic Acetylcholine Receptor (α-9/10 nAChR)

Abstract

Background: The α-9/10 nicotinic acetylcholine receptor is known to be the primary channel through which both vestibular and auditory efferents mediate the inhibition of their respective peripheral hair cells and afferents. With respect to the auditory system, the deletion of the α-9 subunit results in abnormalities in the development of properly functioning cochlear hair cells. Given the high degree of similarity between the au- ditory and the vestibular systems, we hypothesize that α-9 knockout mice should have impaired vestibular hair cell development and consequently compromised vestibular-mediated functions.

Methods: In order to characterize vestibular function in α-9 knockout alert mice, we quantified the vestibu- lo-ocular reflex (VOR) through both gain and phase. Additionally, the optokinetic nystagmus (OKN) was sim- ilarly assessed as a control. VOR in light (VORl) was also quantified to further evaluate VOR and OKN efficacy. Furthermore, as information from the vestibular system mediates postural regulation and head stabilization, we assessed these properties through rotor rod and balance beam paradigms.

Results: Surprisingly, the loss of the α-9 subunit in knockout mice did not result in any attenuation in VOR gain nor deviations in phase compared to wild type. OKN and VORl’s gain and phase values remain similarly unchanged, confirming preserved function within the vestibular nucleus. Descending vestibulospinal infor- mation seems to be unaltered as well, as no significant difference was observed in postural testing.

Limitations: The α-9 knockout mice used specifically had exon 1 and exon 2 of the α-9 gene targeted, which could potentially limit generalizability. Also, frequencies greater than 3Hz were not tested.

Conclusions: Our findings demonstrate that α-9 knockout mice still maintain normal vestibular function.