Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., ND12.200, Dallas, TX, 75390, USA.
Cerebellum. 2018 Oct;17(5):590-600. doi: 10.1007/s12311-018-0951-4.
Cerebellar Purkinje cells (PCs) and cerebellar pathways are primarily affected in many autosomal dominant cerebellar ataxias. PCs generate complex spikes (CS) in vivo when activated by climbing fiber (CF) which rise from the inferior olive. In this study, we investigated the functional state of the CF-PC circuitry in the transgenic mouse model of spinocerebellar ataxia type 2 (SCA2), a polyglutamine neurodegenerative genetic disease. In our experiments, we used an extracellular single-unit recording method to compare the PC activity pattern and the CS shape in age-matched wild-type mice and SCA2-58Q transgenic mice. We discovered no alterations in the CS properties of PCs in aging SCA2 mice. To examine the integrity of the olivocerebellar pathway, we applied harmaline, an alkaloid that acts directly on the inferior olive neurons. The pharmacological stimulation of olivocerebellar circuit by harmaline uncovered disturbances in SCA2-58Q PC activity pattern and in the complex spike shape when compared with age-matched wild-type cells. The abnormalities in the CF-PC circuitry were aggravated with age. We propose that alterations in CF-PC circuitry represent one of potential causes of ataxic symptoms in SCA2 and in other SCAs.
小脑浦肯野细胞（PCs）和小脑通路主要受许多常染色体显性小脑共济失调的影响。当被来自下橄榄核的 climbing fiber（CF）激活时，PCs 在体内产生复杂 spikes（CS）。在这项研究中，我们研究了小脑共济失调 2 型（SCA2）转基因小鼠模型中 CF-PC 回路的功能状态，SCA2 是一种多聚谷氨酰胺神经退行性遗传疾病。在我们的实验中，我们使用了细胞外单单位记录方法来比较同龄野生型和 SCA2-58Q 转基因小鼠的 PC 活动模式和 CS 形状。我们发现，在衰老的 SCA2 小鼠中，PC 的 CS 特性没有改变。为了检查橄榄小脑通路的完整性，我们应用了 harmaline，一种直接作用于下橄榄核神经元的生物碱。与同龄野生型细胞相比，harmaline 对橄榄小脑回路的药理学刺激揭示了 SCA2-58Q PC 活动模式和复杂 spike 形状的紊乱。CF-PC 回路的异常随年龄增长而加剧。我们提出，CF-PC 回路的改变可能是 SCA2 和其他 SCAs 共济失调症状的潜在原因之一。
