In vivo analysis of the spontaneous firing of cerebellar Purkinje cells in awake transgenic mice that model spinocerebellar ataxia type 2.
In vivo analysis of the spontaneous firing of cerebellar Purkinje cells in awake transgenic mice that model spinocerebellar ataxia type 2.
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在清醒的转基因小鼠中对小脑Purkinje细胞自发性射击的体内分析，该小鼠模拟了2型脊椎动物共济失调。
DOI：
10.1016/j.ceca.2020.102319
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发表时间：
2021-01
期刊：
影响因子：
4
通讯作者：
Bezprozvanny IB
中科院分区：
文献类型：
--
作者：
Egorova PA;Gavrilova AV;Bezprozvanny IB
小脑浦肯野细胞 (PC) 以强直模式自发放电，尽管这种起搏活动的精确性在许多涉及小脑萎缩的异常情况下受到干扰，例如许多脊髓小脑共济失调 (SCA)。在我们之前的研究中，我们使用单单元细胞外记录方法来分析麻醉的 SCA2-58Q 转基因小鼠体内的自发 PC 放电。我们意识到，与野生型 (WT) 同窝小鼠的 PC 相比，衰老 SCA2-58Q 小鼠的 PC 放电规律要少得多，并且可以通过腹膜内 (i. p.) 注射 SK 通道阳性调节剂氯唑沙宗 (CHZ) 来逆转这种异常活动。在这里，我们使用相同的单单元细胞外记录方法来分析清醒的SCA2-58Q转基因小鼠体内的自发放电。为此，我们使用 Mobile HomeCage（Neurotar，芬兰）浮动平台在记录过程中固定实验动物的头部。我们发现，与之前观察到的麻醉动物的 PC 相比，清醒动物的 PC 发射的频率通常要高得多，但规律性要低得多。清醒的 SCA2/WT 小鼠的体内记录显示，与 WT 同窝小鼠相比，SCA2 小鼠中 PC 响应攀爬纤维的兴奋而产生的复杂尖峰以及简单尖峰的频率要低得多。为了测试 SK 通道正向调节对清醒 SCA2 小鼠 PC 放电活动的影响以及对其运动协调的影响，我们在这些小鼠中开始了 CHZ 试验。我们发现长期 i。 p。注射 CHZ 并不影响 SCA2-58Q 小鼠的尖峰生成，但它们确实恢复了这种自发起搏活动的精度。此外，我们还表明 CHZ 治疗减轻了 SCA2-58Q 小鼠的年龄依赖性运动障碍。我们认为，PC尖峰生成缺乏精确性可能是不同SCA中共济失调症状进展的关键原因，钙激活钾通道（包括SK通道）的激活可以作为在疾病的生理水平上治疗SCAs的潜在方法。
Cerebellar Purkinje cells (PCs) fire spontaneously in a tonic mode, although the precision of this pacemaking activity is disturbed in many abnormal conditions involving cerebellar atrophy, such as many spinocerebellar ataxias (SCAs). In our previous studies we used the single-unit extracellular recording method to analyze spontaneous PC firing in vivo in the anesthetized SCA2-58Q transgenic mice. We realized that PCs from aging SCA2-58Q mice fire much less regularly compared to PCs from their wild type (WT) littermates and this abnormal activity can be reversed with an intraperitoneal (i. p.) injection of SK channel-positive modulator chlorzoxazone (CHZ). Here we used the same single-unit extracellular recording method to analyze the spontaneous firing in vivo in awake SCA2-58Q transgenic mice. For this purpose, we used the Mobile HomeCage (Neurotar, Finland) floating platform to immobilize the experimental animal’s head during the recording sessions. We discovered that generally PCs from awake animals fired much more frequently and much less regularly than previously observed PCs from anesthetized animals. In vivo recordings from awake SCA2/WT mice revealed that complex spikes, which are generated by PCs in reply to the excitation coming by climbing fibers, as well as simple spikes, were much less frequent in SCA2 mice compared to their WT littermates. To test the effect of the SK channel positive modulation on the PCs firing activity in awake SCA2 mice and also the effect on their motor coordination, we started the CHZ trial in these mice. We discovered that the long-term i. p. injections of CHZ did not affect the spike generation in SCA2-58Q mice, however, they did recover the precision of this spontaneous pacemaking activity. Furthermore, we also showed that treatment with CHZ alleviated the age-dependent motor impairment in SCA2-58Q mice. We propose that the lack of precision in PC spike generation might be a key cause for the progression of ataxic symptoms in different SCAs and that the activation of calcium-activated potassium channels, including SK channels, can be used as a potential way to treat SCAs on the physiological level of the disease.
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影响因子：
5.3
作者：
Hurlock, Edward C.;McMahon, Anne;Joho, Rolf H.
通讯作者：
Joho, Rolf H.
影响因子：
5.7
作者：
Cho, Lily T. -Y.;Alexandrou, Aristos J.;Young, Gareth T.
通讯作者：
Young, Gareth T.
DOI：
10.1111/j.1749-6632.2002.tb07574.x
发表时间：
2002-01-01
期刊：
CREBELLUM: RECENT DEVELOPMENTS IN CEREBELLAR RESEARCH
影响因子：
--
作者：
Ito, M
通讯作者：
Ito, M
影响因子：
5.3
作者：
Dougherty, S. E.;Reeves, J. L.;Cowell, R. M.
通讯作者：
Cowell, R. M.
脊椎小脑共济失调：治疗开发的前景和挑战。
DOI：
10.1038/s41582-018-0051-6
发表时间：
2018-10
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Ashizawa T;Öz G;Paulson HL
通讯作者：
Paulson HL