The mammalian efferent vestibular system plays a crucial role in vestibulo-ocular reflex compensation after unilateral labyrinthectomy
The mammalian efferent vestibular system plays a crucial role in vestibulo-ocular reflex compensation after unilateral labyrinthectomy
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DOI：
10.1152/jn.01049.2015
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发表时间：
2017-04-01
影响因子：
2.5
通讯作者：
Migliaccio, Americo A.
中科院分区：
文献类型：
--
作者：
Hubner, Patrick P.;Khan, Serajul I.;Migliaccio, Americo A.
α 9-烟碱型乙酰胆碱受体（α 9-nAChR）亚单位在前庭和听觉外周中表达，并且其功能丧失可损害来自主要胆碱能传出前庭系统（EVS）的外周输入。最近的一项研究表明，α 9-nAChR在短期前庭眼反射（VOR）适应中起重要作用。我们假设α 9-nAChRs对其他形式的前庭可塑性也很重要，例如前庭器官损伤后VOR恢复所需的可塑性。我们测量了α 9基因敲除小鼠中VOR补偿的功效。这些小鼠具有编码nAChR的大部分基因（chrna 9）的缺失，从而缺乏α 9-nAChR。我们测量了20只α 9基因敲除小鼠和16只cba 129对照小鼠的VOR增益（眼速度/头速度）。我们在单侧椎板切除术（UL）前（基线）以及UL后1、5和28天，在完全黑暗中测量了正弦（0.2-10 Hz，20-100度/s）和瞬态（1，500 - 6，000度/s（2））VOR。在UL后第1天，cba 129小鼠保留了其对侧旋转的初始功能的50%，而α 9敲除小鼠仅保留了20%。28天后，与cba 129小鼠相比，α 9基因敲除小鼠的同侧和对侧旋转增益降低了50%。cba 129小鼠同病灶旋转功能恢复至基线水平的75%，对病灶旋转功能恢复至基线水平的90%。相比之下，类似于9敲除小鼠仅分别恢复了类似于30%和类似于50%的功能，使得VOR在两个方向上的旋转严重受损。我们的研究结果表明，损失的α 9-nAChR严重影响VOR补偿，这表明，补充中枢和外周EVS介导的适应机制可能会受到这种loss.New和值得注意的损失的α 9-烟碱乙酰胆碱受体（α 9- nAChR）的亚基利用传出前庭系统（EVS）已被证明显着影响前庭眼反射（VOR）的适应。在我们目前的研究中，我们已经表明，α 9-nAChRs的损失也影响VOR补偿，这表明哺乳动物EVS在前庭可塑性中起着重要的作用，一般来说，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。
The alpha 9-nicotinic acetylcholine receptor (alpha 9-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 alpha 9-nAChRs play an important role in short-term vestibulo-ocular reflex (VOR) adaptation. We hypothesize that alpha 9-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 alpha 9 knockout mice. These mice have deletion of most of the gene (chrna9) encoding the nAChR and thereby lack alpha 9-nAChRs. We measured the VOR gain (eye velocity/head velocity) in 20 alpha 9 knockout mice and 16 cba129 controls. We measured the sinusoidal (0.2-10 Hz, 20-100 degrees/s) and transient (1,500-6,000 degrees/s(2)) VOR in complete darkness before (baseline) unilateral labyrinthectomy (UL) and then 1, 5, and 28 days after UL. On day 1 after UL, cba129 mice retained similar to 50% of their initial function for contralesional rotations, whereas alpha 9 knockout mice only retained similar to 20%. After 28 days, alpha 9 knockout mice had similar to 50% lower gain for both ipsilesional and contralesional rotations compared with cba129 mice. Cba129 mice regained similar to 75% of their baseline function for ipsilesional and similar to 90% for contralesional rotations. In contrast, similar to 9 knockout mice only regained similar to 30% and similar to 50% function, respectively, leaving the VOR severely impaired for rotations in both directions. Our results show that loss of alpha 9-nAChRs severely affects VOR compensation, suggesting that complimentary central and peripheral EVS-mediated adaptive mechanisms might be affected by this loss.NEW & NOTEWORTHY Loss of the alpha 9-nicotinic acetylcholine receptor (alpha 9- 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 alpha 9-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.