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Ethanol modulates sensory information processing in cerebellar cortex

Ethanol modulates sensory information processing in cerebell...

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中国神经科学学会第十二届全国学术会议

作者： Mao-Cheng Wu Guang-Jian Zhang De-Lai Qiu Key Laboratory of Cellular Function and Pharmacology of Jilin Province Yanbian University

Overdose intake of ethanol can impair cerebellar cortical neurons to integrate and transfer external information, resulting in a dysfunction of cerebellar motor regulation or cerebellar ataxia. We recently investigated the effects of ethanol on sensory stimulation-evoked responses in the cerebellar cortex of urethane-anesthetized mice, by electrophysiological and pharmacological methods. We found that ethanol dosedependently inhibited the facial stimulation evoked field potential responses in cerebellar granule cell layer, whereas ethanol bidirectional modulate the sensory stimulation-evoked responses in molecular layer via GABAA receptor. In vivo patch-clamp recordings showed that ethanol dose-dependently inhibited the facial stimulation-evoked outward currents of cerebellar Purkinje cells（PCs）. The ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1（CB1） antagonists and agonist. The ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway, suggesting that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs. In addition, ethanol inhibited the spontaneous CS-evoked pause in simple spike firing and in the amplitude of the afterhyperpolarization via activation of CB1 receptors in vivo in mice, suggesting that excessive ethanol intake inhibits climbing fiber–PC synaptic transmission by modulating CB1 receptors in the cerebellar cortex.

关键词： Ethanol Cerebellar Purkinje cell sensory stimulation in vivo whole-cell patch-clamp recording complex spike cannabinoids receptor 1 protein kinase A

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