Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, Jilin Province, 133002, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin Province, China.
Department of Neurology, Affiliated Hospital of Yanbian University, Yanji, Jilin Province, China.
Neurosci Lett. 2020 Jan 10;715:134628. doi: 10.1016/j.neulet.2019.134628. Epub 2019 Nov 16.
Ethanol (EtOH) exposure causes alterations of motor coordination, balance, behavior, speech, and certain cognitive functions are considered to be caused partly by impairment of cerebellar circuits function and modulation of synaptic transmission. The cerebellar cortical molecular layer interneuron-Purkinje cell (MLI-PC) synapses are critical for various information integration and transmission, which are sensitive to acute and chronic EtOH exposure. The aim of this study is to investigate the effect of chronic ethanol exposure on the facial stimulation-evoked MLI-PC synaptic transmission in urethane-anesthetized mice, by electrophysiological recording and pharmacological methods. Under current-clamp recording conditions, air-puff stimulation of ipsilateral whisker pad evoked MLI-PC synaptic transmission, which expressed an inhibitory component (P1) followed by a pause of simple spike (SS) firing in cerebellar PCs. Chronic ethanol exposure did not change the latency of the facial stimulation-evoked responses in cerebellar PCs, but induced significant enhancement of the stimulation-evoked MLI-PC synaptic transmission, which expressed increases in amplitude of P1 and pause of SS firing. The amplitude of P1 and pause of SS in ethanol exposure group were significant higher than that in control group. Cerebellar surface application of nitric oxide synthesis (NOS) inhibitor, L-NNA (5 mM) significantly decreased the amplitude of P1 and the pause of SS firing in EtOH exposure group, but did no effect on control group. In contrast, cerebellar surface application of NO donor, SNAP (100 μM) significantly increased the amplitude of P1 and the pause of SS firing in control group, but not in EtOH exposure group. These results indicated that chronic EtOH exposure significantly facilitated the sensory-evoked MLI-PC synaptic transmission via NO signaling pathway in mouse cerebellar cortex.
乙醇（EtOH）暴露会导致运动协调、平衡、行为、言语和某些认知功能的改变，这些改变被认为部分是由于小脑回路功能的损害和突触传递的调节所致。小脑皮质分子层中间神经元-浦肯野细胞（MLI-PC）突触对于各种信息的整合和传递至关重要，这些信息对急性和慢性乙醇暴露敏感。本研究旨在通过电生理记录和药理学方法，研究慢性乙醇暴露对乌拉坦麻醉小鼠面部刺激诱发的 MLI-PC 突触传递的影响。在电流钳记录条件下，同侧胡须垫的空气喷刺激诱发 MLI-PC 突触传递，在小脑浦肯野细胞中表现出抑制性成分（P1），随后简单峰（SS）放电暂停。慢性乙醇暴露并未改变小脑浦肯野细胞对面部刺激诱发反应的潜伏期，但诱导了刺激诱发的 MLI-PC 突触传递的显著增强，表现为 P1 幅度增加和 SS 放电暂停。乙醇暴露组的 P1 幅度和 SS 放电暂停明显高于对照组。小脑表面应用一氧化氮合酶（NOS）抑制剂 L-NNA（5 mM）显著降低了乙醇暴露组 P1 的幅度和 SS 放电暂停，但对对照组没有影响。相反，小脑表面应用一氧化氮供体 SNAP（100 μM）显著增加了对照组 P1 的幅度和 SS 放电暂停，但在乙醇暴露组没有作用。这些结果表明，慢性乙醇暴露通过小鼠小脑皮质中的一氧化氮信号通路显著促进了感觉诱发的 MLI-PC 突触传递。
