title: N-methyl-d-aspartate inhibits cerebellar Purkinje cell activity via the excitation of molecular layer interneurons under in vivo conditions in mice.
abstract: N-methyl-d-aspartate (NMDA) receptors play a key role in synaptic transmission, and are widely expressed on the membrane of granule cells, parallel fibers, and molecular layer interneurons (MLIs) in the cerebellar cortex of mammals. In cerebellar slices, activation of NMDA receptors increases inhibitory postsynaptic currents (IPSCs) of Purkinje cells (PCs). However, the effects of NMDA on the cerebellar network under in vivo conditions are currently unclear. In the present study, we examined the effects of NMDA on the spontaneous activity of PCs and MLIs in urethane-anesthetized mice by electrophysiological, pharmacological, and juxtacellular labeling methods. Our results revealed that cerebellar surface application of NMDA (5-200μM) reduced the PC simple spike (SS) firing rate in a dose-dependent manner. Application of GABAA receptor antagonist, SR95531 (20μM) abolished NMDA-induced inhibition of PCs spontaneous activity, and revealed NMDA-induced excitation of cerebellar PCs. NMDA receptor antagonist, DAP-V (250µM) did not affect the mean frequency of SS firing, but the SS firing rate of PCs became more regular than the control. In addition, NMDA increased the spike firing of both basket-type and stellate-type MLIs. Overall, these results indicated that NMDA-induced excitation of MLIs at the cerebellar surface may inhibit PC activity. Thus, NMDA receptors of MLIs may play a key role in regulating the spontaneous activity of PCs, and in information transmission and integration in cerebellar cortex.
authors.affiliation: Cellular Function Research Center, Yanbian University, 977, GongYuan Road, Yanji City, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Cellular Function Research Center, Yanbian University, 977, GongYuan Road, Yanji City, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Zhao
authors.affiliation: Cellular Function Research Center, Yanbian University, 977, GongYuan Road, Yanji City, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, China.
authors.forename: Guo-Yan
authors.initials: GY
authors.lastname: Zhao
authors.affiliation: Cellular Function Research Center, Yanbian University, 977, GongYuan Road, Yanji City, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Cellular Function Research Center, Yanbian University, 977, GongYuan Road, Yanji City, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, China. Electronic address: cpchu@ybu.edu.cn.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chu
authors.affiliation: Cellular Function Research Center, Yanbian University, 977, GongYuan Road, Yanji City, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, China. Electronic address: dlqiu@ybu.edu.cn.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008813:Mice, Inbred ICR; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques; D014520:Urethane / Q000494:pharmacology
chemical_list: D018686:Anesthetics, Intravenous; D018690:Excitatory Amino Acid Agonists; D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D016194:Receptors, N-Methyl-D-Aspartate; C070614:neurobiotin; D014520:Urethane; D016202:N-Methylaspartate; D001710:Biotin; C049853:gabazine
keywords: Cerebellar; Extracellular recording; GABA(A) receptor; Molecular layer interneuron; NMDA; Purkinje cell