The mammalian efferent vestibular system plays a crucial role in the high-frequency response and short-term adaptation of the vestibuloocular reflex

Abstract

Hübner PP, Khan SI, Migliaccio AA. The mammalian efferent vestibular system plays a crucial role in the high-frequency response and short-term adaptation of the vestibuloocular reflex. J Neurophysiol 114: 3154 -3165, 2015. First published September 30, 2015 doi:10.1152/jn.00307.2015.-Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in ␣9-knockout mice. These mice carry a missense mutation of the gene encoding the ␣9 nicotinic acetylcholine receptor (nAChR) subunit. The ␣9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 ␣9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5ϫ), gain-decrease adaptation (0.5ϫ), or no adaptation (baseline, 1ϫ). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2-10 Hz, 20 -100°/s) and transient (1,500 -6,000°/s 2 ) VOR in complete darkness. ␣9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (ϳ5% Ͻ1 Hz to ϳ25% Ͼ1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in ␣9-knockout mice (17%) compared with control mice (53%), a reduction of ϳ70%. Our results show that the loss of ␣9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity. efferent vestibular system; vestibular adaptation; vestibular plasticity; vestibuloocular reflex; ␣9-knockout mice DESPITE CONSIDERABLE EFFORT, the functional role of the mammalian efferent vestibular system (EVS) is poorly understood.

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

“…As such, under unstimulated normal conditions, efferent inputs could profoundly influence afferent activity. Consistent with the notion that efferents have a significant functional role, ␣9 KO mice (Eron et al, 2015;Hübner et al, 2015Hübner et al, , 2017 and calcitonin gene-related protein KO mice (Luebke et al, 2014) have deficiencies in the vestibulo-ocular reflex response, adaptation, and compensation.…”

“…This notion is supported by vestibular defects in two mouse models with efferent dysfunction. Calcitonin generelated protein (Luebke et al, 2014) and ␣9 (Hübner et al, 2015(Hübner et al, , 2017) KO mice show abnormalities in the development of the vestibulo-ocular reflex response as well as its adaptation and compensation. To date, no studies have attempted to silence the efferents to observe their direct effect on the function of afferents.…”

Nicotinic acetylcholine receptors regulate vestibular afferent gain and activation timing

“…An apparent population shift in the proportion of irregular and regular vestibular afferent fibers following unilateral labyrinthectomy was reported by Sadeghi et al (), and these investigators argued that efferent activity might have mediated such changes during compensation to the injury. Hübner et al () also suggested that the excessive activity of disinhibited type II hair cells in an α9 KO could mediate a shift to more regular discharge activity in dimorph afferents. An additional efferent mechanism may also contribute to a change in discharge regularity.…”

Moderne Schwindeldiagnostik

“…Die Ursache ist nicht vollständig geklärt. Es werden zentrale regulatorische Prozesse aber auch Modulationen der efferenten Nervenbahnen diskutiert [150][151][152][153]154]. Auch Vorschädigungen des VOR-Gain können bei der Bewertung der Ergebnisse des vKIT Schwierigkeiten bereiten.…”