Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability
Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability
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DOI：
10.1523/jneurosci.0067-04.2004
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发表时间：
2004-04-14
影响因子：
5.3
通讯作者：
Valenzuela, CF
中科院分区：
文献类型：
--
作者：
Carta, M;Mameli, M;Valenzuela, CF
酒精中毒会改变协调性和运动技能，这是世界各地大量交通事故相关死亡的原因。虽然乙醇（EtOH）的确切作用机制目前尚不清楚，但研究表明，它的作用部分是通过干扰正常的小脑功能。小脑回路的一个重要组成部分是颗粒细胞。这些大量表达的神经元的兴奋性由高尔基体细胞控制，高尔基体细胞是GABA能中间神经元的一种亚型。颗粒细胞接受GABA能输入的形式相性和紧张性电流，分别由突触和突触外受体介导。使用急性小脑切片制备和膜片钳电生理技术，我们发现，乙醇诱导的自发IPSCs的频率和强直电流的幅度平行增加。当用河豚毒素阻断自发动作电位时，EtOH（50 mM）没有产生这种效果。记录在松散的补丁细胞附着配置表明，乙醇增加高尔基体细胞的自发动作电位的频率。总之，这些发现表明，乙醇增强GABA能抑制颗粒细胞通过突触前机制，涉及增加动作电位依赖的GABA从高尔基体细胞的释放。这种效应可能会对通过小脑皮质的信息流产生影响，并可能有助于急性摄入酒精饮料引起运动障碍的机制。
Alcohol intoxication alters coordination and motor skills, and this is responsible for a significant number of traffic accident-related deaths around the world. Although the precise mechanism of action of ethanol (Et0H) is presently unknown, studies suggest that it acts, in part, by interfering with normal cerebellar functioning. An important component of cerebellar circuits is the granule cell. The excitability of these abundantly expressed neurons is controlled by the Golgi cell, a subtype of GABAergic interneuron. Granule cells receive GABAergic input in the form of phasic and tonic currents that are mediated by synaptic and extrasynaptic receptors, respectively. Using the acute cerebellar slice preparation and patch-clamp electrophysiological techniques, we found that ethanol induces a parallel increase in both the frequency of spontaneous IPSCs and the magnitude of the tonic current. EtOH (50 mM) did not produce this effect when spontaneous action potentials were blocked with tetrodotoxin. Recordings in the loose-patch cell-attached configuration demonstrated that ethanol increases the frequency of spontaneous action potentials in Golgi cells. Taken together, these findings indicate that ethanol enhances GABAergic inhibition of granule cells via a presynaptic mechanism that involves an increase in action potential-dependent GABA release from Golgi cells. This effect is likely to have an impact on the flow of information through the cerebellar cortex and may contribute to the mechanism by which acute ingestion of alcoholic beverages induces motor impairment.