Idoux Erwin, Tagliabue Michele, Beraneck Mathieu
Center for Neurophysics, Physiology, Pathology, CNRS UMR 8119, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Centre National D'Etudes Spatiales, Paris, France.
Front Neurol. 2018 Nov 12;9:918. doi: 10.3389/fneur.2018.00918. eCollection 2018.
Motion sickness occurs when the vestibular system is subjected to conflicting sensory information or overstimulation. Despite the lack of knowledge about the actual underlying mechanisms, several drugs, among which scopolamine, are known to prevent or alleviate the symptoms. Here, we aim at better understanding how motion sickness affects the vestibular system, as well as how scopolamine prevents motion sickness at the behavioral and cellular levels. We induced motion sickness in adult mice and tested the vestibulo-ocular responses to specific stimulations of the semi-circular canals and of the otoliths, with or without scopolamine, as well as the effects of scopolamine and muscarine on central vestibular neurons recorded on brainstem slices. We found that both motion sickness and scopolamine decrease the efficacy of the vestibulo-ocular reflexes and propose that this decrease in efficacy might be a protective mechanism to prevent later occurrences of motion sickness. To test this hypothesis, we used a behavioral paradigm based on visuo-vestibular interactions which reduces the efficacy of the vestibulo-ocular reflexes. This paradigm also offers protection against motion sickness, without requiring any drug. At the cellular level, we find that depending on the neuron, scopolamine can have opposite effects on the polarization level and firing frequency, indicating the presence of at least two types of muscarinic receptors in the medial vestibular nucleus. The present results set the basis for future studies of motion sickness counter-measures in the mouse model and offers translational perspectives for improving the treatment of affected patients.
当前庭系统接收到相互矛盾的感觉信息或受到过度刺激时，就会发生晕动病。尽管对实际的潜在机制尚缺乏了解，但已知几种药物，其中包括东莨菪碱，可预防或减轻症状。在此，我们旨在更好地了解晕动病如何影响前庭系统，以及东莨菪碱在行为和细胞水平上如何预防晕动病。我们在成年小鼠中诱发晕动病，并测试了在有或没有东莨菪碱的情况下，前庭眼反射对半规管和耳石特定刺激的反应，以及东莨菪碱和毒蕈碱对脑干切片上记录的中枢前庭神经元的影响。我们发现晕动病和东莨菪碱都会降低前庭眼反射的功效，并提出这种功效降低可能是一种预防晕动病再次发生的保护机制。为了验证这一假设，我们使用了一种基于视觉 - 前庭相互作用的行为范式，该范式降低了前庭眼反射的功效。这种范式也能提供抗晕动病的保护作用，而无需任何药物。在细胞水平上，我们发现根据神经元的不同，东莨菪碱可对极化水平和放电频率产生相反的影响，这表明在内侧前庭核中至少存在两种类型的毒蕈碱受体。目前的研究结果为未来在小鼠模型中研究晕动病对策奠定了基础，并为改善受影响患者的治疗提供了转化前景。
