The role of regularity and synchrony of cerebellar Purkinje cells for pathological nystagmus
The role of regularity and synchrony of cerebellar Purkinje cells for pathological nystagmus
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DOI：
10.1111/j.1749-6632.2011.06149.x
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发表时间：
2011-01-01
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影响因子：
--
通讯作者：
Strupp, Michael
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文献类型：
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作者：
Glasauer, Stefan;Roessert, Christian;Strupp, Michael
以往的理论认为，钾通道阻滞剂4-氨基吡啶(4-AP)对下拍性眼球震颤(DBN)或发作性共济失调2型(EA2)患者的有利作用是由于小脑浦肯野细胞(PC)兴奋性的增加。最近用治疗剂量的4-AP在EA2小鼠模型上的实验结果挑战了4-AP不改变PC的放电频率而是它们的规律性的理论。基于眼球运动和小脑回路的数学模型，我们表明，在PC放电过程中，如果没有同步性，规律性的变化是没有影响的。与同步放电一起，规律性的增加可能导致总体抑制的减少，并可能将抑制逆转为由于印记而产生的兴奋反应，这是同步神经抑制的一种新效应。这两种作用不太可能是4-AP成功治疗小脑疾病的致病机制。
Previous theories assumed that the beneficial effect of the potassium channel blocker 4-aminopyridine (4-AP) for patients suffering from downbeat nystagmus (DBN) or episodic ataxia type 2 (EA2) is due to an increase of excitability of cerebellar Purkinje cells (PC). Recent experimental results using therapeutic doses of 4-AP with a mouse model of EA2 challenged the theory showing that 4-AP does not change the firing rate of PC but their regularity. Based on a mathematical model of the ocular motor and cerebellar circuitry, we show that changes in regularity have no effect without synchrony in PC firing. Together with synchronous firing, an increase in regularity may lead to a decrease in overall inhibition and may invert the inhibitory to an excitatory response due to imprinting, a novel effect of synchronized neural inhibition. Both effects are unlikely to be the causative mechanism for the success of 4-AP in treating cerebellar disorders.