title: N-methyl-D-Aspartate Receptors Contribute to Complex Spike Signaling in Cerebellar Purkinje Cells: An In vivo Study in Mice.
abstract: N-methyl-D-aspartate receptors (NMDARs) are post-synaptically expressed at climbing fiber-Purkinje cell (CF-PC) synapses in cerebellar cortex in adult mice and contributed to CF-PC synaptic transmission under in vitro conditions. In this study, we investigated the role of NMDARs at CF-PC synapses during the spontaneous complex spike (CS) activity in cerebellar cortex in urethane-anesthetized mice, by in vivo whole-cell recording technique and pharmacological methods. Under current-clamp conditions, cerebellar surface application of NMDA (50 μM) induced an increase in the CS-evoked pause of simple spike (SS) firing accompanied with a decrease in the SS firing rate. Under voltage-clamp conditions, application of NMDA enhanced the waveform of CS-evoked inward currents, which expressed increases in the area under curve (AUC) and spikelet number of spontaneous CS. NMDA increased the AUC of spontaneous CS in a concentration-dependent manner. The EC50 of NMDA for increasing AUC of spontaneous CS was 33.4 μM. Moreover, NMDA significantly increased the amplitude, half-width and decay time of CS-evoked after-hyperpolarization (AHP) currents. Blockade of NMDARs with D-(-)-2-amino-5-phosphonopentanoic acid (D-APV, 250 μM) decreased the AUC, spikelet number, and amplitude of AHP currents. In addition, the NMDA-induced enhancement of CS activity could not be observed after α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors were blocked. The results indicated that NMDARs of CF-PC synapses contributed to the spontaneous CS activity by enhancing CS-evoked inward currents and AHP currents.
authors.affiliation: Cellular Function Research Center, Yanbian UniversityYanji, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian UniversityYanji, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Cellular Function Research Center, Yanbian UniversityYanji, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian UniversityYanji, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Cellular Function Research Center, Yanbian UniversityYanji, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian UniversityYanji, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Bing
authors.affiliation: Cellular Function Research Center, Yanbian University Yanji, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chu
authors.affiliation: Cellular Function Research Center, Yanbian UniversityYanji, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian UniversityYanji, China; Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular of the Ministry of Education, Yanbian UniversityYanji, China.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
keywords: N-methyl-D-aspartate (NMDA); after-hyperpolarization (AHP); cerebellar purkinje cell; complex spike (CS); in vivo whole-cell patch-clamp recording