Vestibular compensation after unilateral labyrinthectomy: Normal versus cerebellar dysfunctional mice
Vestibular compensation after unilateral labyrinthectomy: Normal versus cerebellar dysfunctional mice
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DOI：
10.2310/7070.2007.0050
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发表时间：
2007-12-01
期刊：
影响因子：
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通讯作者：
Cullen, Kathleen E.
中科院分区：
文献类型：
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作者：
Aleisa, Mohammad;Zeitouni, Anthony G.;Cullen, Kathleen E.
简介：前庭信息从一个迷路的损失产生显着的不对称的姿势和眼运动控制，解决随着时间的推移。最近的事态发展，在小鼠基因工程，这使得转基因和基因敲除突变小鼠的产生，提供了一个独特的机会，桥梁之间的差距差距的分子机制，补偿和behavior.Method：我们比较了补偿后，在野生型小鼠和小脑功能障碍小鼠（Lurcher突变体）的单侧小脑切除术。Lurcher突变体的特征在于离子型谷氨酸受体δ 2亚基基因中的点突变，其导致所有浦肯野细胞的丧失。为了进一步研究这个问题，我们的特点是前庭补偿的突变小鼠，完全缺乏小脑Purkinje cells.Results的应变：静态体征解决野生型小鼠在24小时内，但没有完全解决在Lurcher小鼠。动态体征通过前庭眼反射（VOR）和前庭颈反射（VCR）的定量分析进行评价。在0.5 Hz下评估的VOR表现出从第1天到第5天的增加，野生型小鼠在第20天达到对照水平。相比之下，Lurcher突变小鼠在同一时期表现出明显较少的补偿。突变小鼠的VOR补偿对高加速度推力的反应略强，但从未达到对照水平。同样，VCR收益表现出有限的补偿，并保持低于正常的突变mice.Conclusion：补偿动力学体征开始在第5天后，在正常小鼠单侧histothecombination。小脑功能障碍的突变小鼠不补偿静态体征，仅对动态体征显示有限的前庭补偿。我们的结论是，其他非小脑途径前庭补偿存在，我们的研究结果强调，这些需要进一步探讨。
Introduction: Loss of vestibular information from one labyrinth produces marked asymmetries of postural and ocular motor control, which resolve over time. Recent developments in mouse genetic engineering, which allow the generation of transgenic and knockout mutant mice, provide a unique opportunity to bridge the gap between the molecular mechanisms that underlie compensation and behaviour.Method: We compared compensation following unilateral labyrinthectomy in wild-type mice and a cerebellar-dysfunctional mouse (the Lurcher mutant). The Lurcher mutant is characterized by a point mutation in the ionotropic glutamate receptor delta2 subunit gene that results in loss of all Purkinje cells. To further investigate this question, we characterized vestibular compensation in a strain of mutant mice that completely lack cerebellar Purkinje cells.Results: Static signs resolved within 24 hours in wild-type mice but did not fully resolve in Lurcher mice. Dynamic signs were evaluated by the quantitative analysis of vestibulo-ocular (VOR) and vestibulocollic (VCR) reflexes. The VOR assessed at 0.5 Hz exhibited increasing gain from day 1 to day 5, reaching control levels by day 20 for the wild-type mice. In contrast, Lurcher mutant mice showed significantly less compensation over this same period. VOR compensation in the mutant mice was slightly more robust in response to high acceleration thrusts but again never reached control levels. Similarly, VCR gains showed limited compensation and remained subnormal in mutant mice.Conclusion: Compensation for dynamic signs starts at day 5 after unilateral labyrinthectomy in normal mice. Cerebellar dysfunctional mutant mice do not compensate for static signs and show limited vestibular compensation for dynamic signs only. We conclude that other noncerebellar pathways for vestibular compensation exist, and our findings emphasize the need for these to be further explored.