title: The mammalian efferent vestibular system plays a crucial role in the high-frequency response and short-term adaptation of the vestibuloocular reflex.
abstract: 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 α9-knockout mice. These mice carry a missense mutation of the gene encoding the α9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 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 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5×), gain-decrease adaptation (0.5×), or no adaptation (baseline, 1×). 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. α9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (∼ 5% <1 Hz to ∼ 25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ∼ 70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity.
authors.affiliation: Balance and Vision Laboratory, Neuroscience Research Australia, Sydney, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, Australia; and.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Hübner
authors.affiliation: Balance and Vision Laboratory, Neuroscience Research Australia, Sydney, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, Australia; and.
authors.forename: Serajul I
authors.initials: SI
authors.lastname: Khan
authors.affiliation: Balance and Vision Laboratory, Neuroscience Research Australia, Sydney, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, Australia; and Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland a.migliaccio@neura.edu.au.
authors.forename: Americo A
authors.initials: AA
authors.lastname: Migliaccio
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005133:Eye Movements; D005260:Female; D008297:Male; D051379:Mice; D009476:Neurons, Efferent / Q000378:metabolism / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D012027:Reflex, Vestibulo-Ocular; D014722:Vestibule, Labyrinth / Q000166:cytology / Q000502:physiology*
chemical_list: D011978:Receptors, Nicotinic; C443079:nAChR alpha9
keywords: efferent vestibular system; vestibular adaptation; vestibular plasticity; vestibuloocular reflex; α9-knockout mice