title: Ethanol Modulates the Spontaneous Complex Spike Waveform of Cerebellar Purkinje Cells Recordedin vivoin Mice.
abstract: Cerebellar Purkinje cells (PCs) are sensitive to ethanol, but the effect of ethanol on spontaneous complex spike (CS) activity in these cellsin vivois currently unknown. Here, we investigated the effect of ethanol on spontaneous CS activity in PCs in urethane-anesthetized mice usingin vivopatch-clamp recordings and pharmacological manipulation. Ethanol (300 mM) induced a decrease in the CS-evoked pause in simple spike (SS) firing and in the amplitude of the afterhyperpolarization (AHP) under current clamp conditions. Under voltage-clamp conditions, ethanol significantly decreased the area under the curve (AUC) and the number of CS spikelets, without changing the spontaneous frequency of the CSs or the instantaneous frequency of the CS spikelets. Ethanol-induced a decrease in the AUC of spontaneous CSs was concentration dependent. The EC50of ethanol for decreasing the AUC of spontaneous CSs was 168.5 mM. Blocking N-methyl-D-aspartate receptors (NMDARs) failed to prevent the ethanol-induced decreases in the CS waveform parameters. However, blockade of cannabinoid receptor 1 (CB1) significantly suppressed the ethanol-induced effects on the CS-evoked pause in SS firing, amplitude of the AHP, spikelet number and the AUC of CSs. Moreover, a CB1 receptor agonist not only reduced the number of spikelets and the AUC of CSs, but also prevented the ethanol-induced inhibition of CS activity. Our results indicate that ethanol inhibits CS activity via activation of the CB1 receptorin vivoin mice, suggesting that excessive ethanol intake inhibits climbing fiber (CF)-PC synaptic transmission by modulating CB1 receptors in the cerebellar cortex.
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, YanBian UniversityYanji City, China; Department of Pain, Affiliated Hospital of Yanbian UniversityYanji City, China.
authors.forename: Guang-Jian
authors.initials: GJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, YanBian UniversityYanji City, China; Department of Osteology, Affiliated Hospital of Yanbian UniversityYanji City, China.
authors.forename: Mao-Cheng
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, YanBian UniversityYanji City, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian UniversityYanji City, China.
authors.forename: Jin-Di
authors.initials: JD
authors.lastname: Shi
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, YanBian UniversityYanji City, China; Department of Neurology, Affiliated Hospital of Yanbian UniversityYanji City, China.
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, YanBian University Yanji City, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chu
authors.affiliation: Department of Neurology, Affiliated Hospital of Yanbian University Yanji City, China.
authors.forename: Song-Biao
authors.initials: SB
authors.lastname: Cui
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, YanBian UniversityYanji City, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian UniversityYanji City, China.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
keywords: after-hyperpolarization (AHP); cannabinoids receptor 1 (CB1); cerebellar Purkinje cell; complex spike (CS); ethanol; in vivo whole-cell patch-clamp recording