T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning
T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning
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DOI：
10.1073/pnas.1311686110
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发表时间：
2013-12-10
影响因子：
11.1
通讯作者：
Feltz, Anne
中科院分区：
文献类型：
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作者：
Ly, Romain;Bouvier, Guy;Feltz, Anne
Ca(V)3.1 t型通道在平行纤维和浦肯野细胞之间的小脑突触中丰富，它们有助于突触去极化。到目前为止，这些通道既没有作为电荷载体，也没有作为Ca2+载体具有特定的生理功能。在这里，我们分析了它们在突触可塑性、运动行为和小脑运动学习中的作用，并比较了WT动物和t型通道功能因基因缺失或急性药物阻断而被消除的小鼠。在细胞水平上，我们发现平行纤维-浦肯野细胞突触的长期增强需要Ca(V)3.1通道。此外，对KO小鼠浦肯野细胞基底单峰放电进行了修饰。急性或慢性t型电流阻断导致运动性能受损，特别是当需要良好的身体平衡时。因为运动行为整合了反射和过去学习行为的记忆，这表明学习能力受损。事实上，对KO小鼠进行前庭-眼反射相位反转测试显示小脑依赖性运动学习受损。这些数据确定了低压激活钙通道在突触可塑性中的作用，并建立了Ca(V)3.1通道在小脑学习中的作用。
Ca(V)3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca2+ carriers. Here we analyze their incidence on synaptic plasticity, motor behavior, and cerebellar motor learning, comparing WT animals and mice where T-type channel function has been abolished either by gene deletion or by acute pharmacological blockade. At the cellular level, we show that Ca(V)3.1 channels are required for long-term potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T-type current blockade results in impaired motor performance in particular when a good body balance is required. Because motor behavior integrates reflexes and past memories of learned behavior, this suggests impaired learning. Indeed, subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals impaired cerebellum-dependent motor learning. These data identify a role of low-voltage activated calcium channels in synaptic plasticity and establish a role for Ca(V)3.1 channels in cerebellar learning.