title: Effects of norepinephrine on spontaneous firing activity of cerebellar Purkinje cells in vivo in mice.
abstract: Norepinephrine (NE), from the locus coeruleus (LC), has been supported to affect GABAergic system and parallel fiber (PF)-Purkinje cell (PC) synaptic transmission via adrenoceptor in cerebellum cortex. However, the effects of NE on the spontaneous spike activity of cerebellar PCs in living mouse have not yet been fully understood. We here examined the effects of NE on the spontaneous activity of PC in urethane-anesthetized mice by electrophysiological and pharmacological methods. Cerebellar surface application of NE (2.5-25μM) reduced the PC simple spike (SS) firing rate in a dose-dependent manner. The half-inhibitory concentration (IC50) was 5.97μM. In contrast, NE significantly increased the spontaneous firing rate of molecular layer interneuron (MLI). Application of GABAA receptor antagonist, gabazine (SR95531, 20μM) not only blocked the NE-induced inhibition of PC SS firing but also revealed NE-induced excitation of cerebellar PC. Blocking AMPA receptors activity enhanced NE-induced inhibition of PC spontaneous activity. Moreover, the effects of NE on PC spontaneous activity were abolished by simultaneously blocking GABAA and AMPA receptors activity. These results indicated that NE bidirectional modulated the spontaneous activity of PCs via enhancing both inhibitory inputs from MLIs and excitatory inputs of parallel fibers, but NE-induced enhance of inhibitory inputs overwhelmed the excitatory inputs under in vivo conditions.
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Guo
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Feng
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
authors.affiliation: College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China. Electronic address: piaorl@ybu.edu.cn.
authors.forename: Ri-Long
authors.initials: RL
authors.lastname: Piao
authors.affiliation: Cellular Function Research Center, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China; College of Medicine, Yanbian University, 977 GongYuan Road, Yanji City, Jilin Province, 133002, China. Electronic address: cpchu@ybu.edu.cn.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D058787:GABA-A Receptor Antagonists; D051379:Mice; D008813:Mice, Inbred ICR; D009638:Norepinephrine / Q000008:administration & dosage*; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology*; D011724:Pyridazines / Q000008:administration & dosage; D011810:Quinoxalines / Q000008:administration & dosage; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D011963:Receptors, GABA-A / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D011810:Quinoxalines; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C049853:gabazine; D009638:Norepinephrine
keywords: AMPA receptor; GABA(A) receptor; Molecular layer interneuron; Norepinephrine; Purkinje cell; Spontaneous activity