Graduate Institute of Electronics Engineering, National Taiwan University, Taipei, Taiwan.
Alcohol Clin Exp Res. 2012 Dec;36(12):2110-6. doi: 10.1111/j.1530-0277.2012.01818.x. Epub 2012 May 7.
Alcohol is a widely abused substance and is responsible for significant morbidity and mortality worldwide. The precise mechanisms underlying ethanol (EtOH)'s actions in the central nervous system (CNS) remain elusive. In vitro studies suggest that GABAergic interneurons are important targets of EtOH action in the CNS. Although EtOH generally acts to inhibit CNS neurons, it appears to cause an increase in GABAergic interneuron excitability. However, it has yet to be demonstrated that EtOH produces this effect in the brain of behaving animals. Here, we demonstrate for the first time that acute EtOH exposure excites a subtype of GABAergic interneuron (cerebellar Golgi cell [GoC]) in a freely moving animal.
Electrophysiological recordings were made from microwire arrays implanted in the anterior cerebellum of freely moving rats.
Cerebellar GoCs display a slow, irregular, spontaneous action potential firing pattern under control conditions. EtOH caused dramatic and consistent increases in the rate and regularity of GoC discharges, including a redistribution of the power in the GoC spike train, such that power became concentrated in the 26.7 ± 7.3 Hz region.
Taken together with our previous findings, these data suggest that a major mechanism of EtOH actions on cerebellar function is an EtOH-induced de-afferentation at the input stage of the cerebellar cortex in the form of granule cell inhibition, and that this inhibition is caused by an increase in GoC firing. It is likely that GoCs may play a significant role both in the gating of information transmission to granule cells and in the modulation of the overall excitability of the cerebellum by tonically controlling granule cell activity.
酒精是一种广泛滥用的物质，在全球范围内造成了重大的发病率和死亡率。乙醇（EtOH）在中枢神经系统（CNS）中的作用的确切机制仍难以捉摸。体外研究表明，γ-氨基丁酸能中间神经元是 EtOH 在中枢神经系统中作用的重要靶点。尽管 EtOH 通常抑制中枢神经系统神经元，但它似乎导致 GABA 能中间神经元兴奋性增加。然而，尚未证明 EtOH 在行为动物的大脑中产生这种效应。在这里，我们首次证明，在自由活动的动物中，急性 EtOH 暴露会兴奋 GABA 能中间神经元（小脑高尔基细胞[GoC]）的一种亚型。
在自由移动大鼠的前小脑植入微丝阵列进行电生理记录。
小脑 GoC 在对照条件下显示出缓慢、不规则的自发性动作电位发放模式。EtOH 导致 GoC 放电率和规律性的急剧和一致增加，包括 GoC 尖峰列车的功率重新分布，使得功率集中在 26.7±7.3 Hz 区域。
这些数据与我们之前的发现一起表明，EtOH 对小脑功能的主要作用机制是 EtOH 诱导的去传入，形式为颗粒细胞抑制，小脑皮层输入阶段的传入，这种抑制是由 GoC 放电增加引起的。GoC 很可能在颗粒细胞活动的整体兴奋性调制以及通过控制颗粒细胞活动的紧张性来调节信息传递到颗粒细胞的门控中发挥重要作用。
