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.
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
J Neurophysiol. 2015 Dec;114(6):3154-65. doi: 10.1152/jn.00307.2015. Epub 2015 Sep 30.
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.
尽管在解剖学上已有详尽描述，但哺乳动物传出前庭系统（EVS）的功能作用仍不清楚。与鱼类和爬行动物不同，哺乳动物的EVS似乎在预期主动头部运动时对初级传入活动的调节中不起作用。然而，它可能在调节需要可塑性的长期机制（如前庭适应）中发挥作用。我们测量了α9基因敲除小鼠的前庭眼反射（VOR）适应效果。这些小鼠携带编码α9烟碱型乙酰胆碱受体（nAChR）亚基的基因错义突变。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为胆碱能的EVS的外周输入。我们测量了26只α9基因敲除小鼠和27只cba129对照小鼠的VOR增益（眼速度/头速度）。小鼠被随机分为三组之一：增益增加适应组（1.5倍）、增益降低适应组（0.5倍）或无适应组（基线，1倍）。在适应训练（以0.5 Hz的水平旋转，峰值速度为20°/秒）后，我们在完全黑暗中测量了正弦波（0.2 - 10 Hz，20 - 100°/秒）和瞬态（1500 - 6000°/秒²）VOR。与对照小鼠相比，α9基因敲除小鼠的基线增益显著更低。这种差异随刺激频率增加（<1 Hz时约为5%，>1 Hz时约为25%）。此外，与对照小鼠（53%）相比，α9基因敲除小鼠的前庭适应（增益增加和增益降低适应组的VOR增益差异占增益增加的百分比）显著降低（17%），降低了约70%。我们的结果表明，α9 nAChRs的缺失对VOR有中度影响，但对VOR适应有严重影响，这表明EVS在前庭可塑性中起关键作用。
