Hübner Patrick P, Khan Serajul I, Migliaccio Americo A
Balance and Vision Laboratory, Neuroscience Research Australia, Sydney, New South Wales, Australia.
University of New South Wales, Sydney, New South Wales, Australia; and.
J Neurophysiol. 2017 Apr 1;117(4):1553-1568. doi: 10.1152/jn.01049.2015. Epub 2017 Jan 11.
The α9-nicotinic acetylcholine receptor (α9-nAChR) subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic efferent vestibular system (EVS). A recent study has shown that α9-nAChRs play an important role in short-term vestibulo-ocular reflex (VOR) adaptation. We hypothesize that α9-nAChRs could also be important for other forms of vestibular plasticity, such as that needed for VOR recovery after vestibular organ injury. We measured the efficacy of VOR compensation in α9 knockout mice. These mice have deletion of most of the gene () encoding the nAChR and thereby lack α9-nAChRs. We measured the VOR gain (eye velocity/head velocity) in 20 α9 knockout mice and 16 cba129 controls. We measured the sinusoidal (0.2-10 Hz, 20-100°/s) and transient (1,500-6,000°/s) VOR in complete darkness before (baseline) unilateral labyrinthectomy (UL) and then 1, 5, and 28 days after UL. On after UL, cba129 mice retained ~50% of their initial function for contralesional rotations, whereas α9 knockout mice only retained ~20%. After 28 days, α9 knockout mice had ~50% lower gain for both ipsilesional and contralesional rotations compared with cba129 mice. Cba129 mice regained ~75% of their baseline function for ipsilesional and ~90% for contralesional rotations. In contrast, α9 knockout mice only regained ~30% and ~50% function, respectively, leaving the VOR severely impaired for rotations in both directions. Our results show that loss of α9-nAChRs severely affects VOR compensation, suggesting that complimentary central and peripheral EVS-mediated adaptive mechanisms might be affected by this loss. Loss of the α9-nicotinic acetylcholine receptor (α9-nAChR) subunit utilized by the efferent vestibular system (EVS) has been shown to significantly affect vestibulo-ocular reflex (VOR) adaptation. In our present study we have shown that loss of α9-nAChRs also affects VOR compensation, suggesting that the mammalian EVS plays an important role in vestibular plasticity, in general, and that VOR compensation is a more distributed process than previously thought, relying on both central and peripheral changes.
α9烟碱型乙酰胆碱受体（α9-nAChR）亚基在前庭和听觉外周表达，其功能丧失可能会损害主要由胆碱能传出前庭系统（EVS）提供的外周输入。最近的一项研究表明，α9-nAChRs在短期前庭眼反射（VOR）适应中起重要作用。我们假设α9-nAChRs对于其他形式的前庭可塑性也可能很重要，例如前庭器官损伤后VOR恢复所需的可塑性。我们测量了α9基因敲除小鼠中VOR补偿的效能。这些小鼠缺失了编码nAChR的大部分基因（），因此缺乏α9-nAChRs。我们测量了20只α9基因敲除小鼠和16只cba129对照小鼠的VOR增益（眼速度/头速度）。我们在完全黑暗中测量了单侧迷路切除术（UL）前（基线）、UL后1天、5天和28天的正弦（0.2 - 10 Hz，20 - 100°/s）和瞬态（1500 - 6000°/s）VOR。在UL后，cba129小鼠对侧旋转保留了约50%的初始功能，而α9基因敲除小鼠仅保留了约20%。28天后，与cba129小鼠相比，α9基因敲除小鼠同侧和对侧旋转的增益均降低了约50%。Cba129小鼠同侧旋转恢复了约75%的基线功能，对侧旋转恢复了约90%。相比之下，α9基因敲除小鼠分别仅恢复了约30%和50%的功能，导致VOR在两个方向的旋转中严重受损。我们的结果表明，α9-nAChRs的缺失严重影响VOR补偿，这表明互补的中枢和外周EVS介导的适应性机制可能会受到这种缺失的影响。传出前庭系统（EVS）所利用的α9烟碱型乙酰胆碱受体（α9-nAChR）亚基的缺失已被证明会显著影响前庭眼反射（VOR）适应。在我们目前的研究中，我们表明α9-nAChRs的缺失也会影响VOR补偿，这表明哺乳动物的EVS总体上在前庭可塑性中起重要作用，并且VOR补偿是一个比以前认为的更分散的过程，依赖于中枢和外周的变化。
