Abstract
The functional role of the mammalian efferent vestibular system (EVS) is not fully understood. One proposal is that the mammalian EVS plays a role in the long-term calibration of central vestibular pathways, for example during development. Here to test this possibility, we studied vestibular function in mice lacking a functional α9 subunit of the nicotinic acetylcholine receptor (nAChR) gene family, which mediates efferent activation of the vestibular periphery. We focused on an α9 (−/−) model with a deletion in exons 1 and 2. First, we quantified gaze stability by testing vestibulo-ocular reflex (VOR, 0.2–3 Hz) responses of both α9 (−/−) mouse models in dark and light conditions. VOR gains and phases were comparable for both α9 (−/−) mutants and wild-type controls. Second, we confirmed the lack of an effect from the α9 (−/−) mutation on central visuo-motor pathways/eye movement pathways via analyses of the optokinetic reflex (OKR) and quick phases of the VOR. We found no differences between α9 (−/−) mutants and wild-type controls. Third and finally, we investigated postural abilities during instrumented rotarod and balance beam tasks. Head movements were quantified using a 6D microelectromechanical systems (MEMS) module fixed to the mouse’s head. Compared to wild-type controls, we found head movements were strikingly altered in α9 (−/−) mice, most notably in the pitch axis. We confirmed these later results in another α9 (−/−) model, with a deletion in the exon 4 region. Overall, we conclude that the absence of the α9 subunit of nAChRs predominately results in an impairment of posture rather than gaze.
Highlights
The mammalian efferent vestibular system (EVS) projects from the brainstem to the inner ear and is theoretically well placed to modulate the afferent output of the peripheral vestibular organs
We tested the vestibular function of mice lacking the α9 subunit of nicotinic acetylcholine receptors
We first quantified vestibular function by measuring the eye movements generated by the vestibulo-ocular reflex (VOR), which functions to ensure gaze stability during head motion
Summary
The mammalian efferent vestibular system (EVS) projects from the brainstem to the inner ear and is theoretically well placed to modulate the afferent output of the peripheral vestibular organs (reviewed in Cullen and Wei, 2021). The. Posture in α-9 KO Mice primary neurotransmitter of the efferent system is acetylcholine, a diverse expression of other neuromodulators including calcitonin gene-related peptide (CGRP), 5 triphosphate (ATP), GABA, and neuronal nitric oxide synthase (nNos) are present at the synapse (Yamashita et al, 1993; Soto and Vega, 2010, and reviewed in Holt et al, 2010). Vestibular hair cells are characterized by α9 and α10 containing nAChRs (Hiel et al, 1996; Anderson et al, 1997; Elgoyhen et al, 2001; Luebke et al, 2005; Morley et al, 2017). Α9/10 nAChRs open calcium-dependent potassium (SK) channels, which hyperpolarizes the hair cell to inhibit neurotransmitter release (Kong et al, 2008; Turcan et al, 2010; Im, 2012)
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