Previously, an Essential Tremor-like phenotype has been noted in animals with a global knockout of the GABA_Aα1 subunit. Given the hypothesized role of the cerebellum in tremor, including Essential Tremor, we used transgenic mice to selectively knock out the GABA_Aα1 subunit from cerebellar Purkinje cells. We examined the resulting phenotype regarding impacts on inhibitory postsynaptic currents, survival rates, gross motor abilities, and expression of tremor. Purkinje cell specific knockout of the GABA_Aα1 subunit abolished all GABA_A-mediated inhibition in Purkinje cells, while leaving GABA_A-mediated inhibition to cerebellar molecular layer interneurons intact. Selective loss of GABA_Aα1 from Purkinje cells did not produce deficits on the accelerating rotarod, nor did it result in decreased survival rates. However, a tremor phenotype was apparent, regardless of sex or background strain. This tremor mimicked the tremor seen in animals with a global knockout of the GABA_Aα1 subunit, and, like Essential Tremor in patients, was responsive to ethanol. These findings indicate that reduced inhibition to Purkinje cells is sufficient to induce a tremor phenotype, highlighting the importance of the cerebellum, inhibition, and Purkinje cells, in tremor.

中文翻译：

---

从浦肯野细胞中选择性丢失 GABAAα1 亚基足以诱导震颤表型。

以前，在 GABA _Aα1亚基被全球敲除的动物中发现了一种类似原发性震颤的表型。鉴于小脑在震颤中的假设作用，包括特发性震颤，我们使用转基因小鼠从小脑浦肯野细胞中选择性地敲除 GABA _Aα1亚基。我们检查了由此产生的表型对抑制性突触后电流、存活率、粗大运动能力和震颤表达的影响。GABA _Aα1亚基的浦肯野细胞特异性敲除消除了浦肯野细胞中所有 GABA _A介导的抑制，同时保留了 GABA _A介导的对小脑分子层中间神经元的抑制。GABA _{Aα1 的}选择性丢失来自浦肯野细胞的加速旋转棒没有产生缺陷，也没有导致存活率降低。然而，无论性别或背景应变如何，震颤表型都很明显。这种震颤模仿了在 GABA _Aα1亚基被整体敲除的动物身上看到的震颤，并且像患者的原发性震颤一样，对乙醇有反应。这些发现表明，降低对浦肯野细胞的抑制足以诱导震颤表型，突出了小脑、抑制和浦肯野细胞在震颤中的重要性。