PMID- 35770634 OWN - NLM STAT- MEDLINE DCOM- 20220701 LR - 20220701 IS - 0371-0874 (Print) IS - 0371-0874 (Linking) VI - 74 IP - 3 DP - 2022 Jun 25 TI - [Noradrenaline modulates the spontaneous firing activities of Purkinje cells via alpha2-adrenergic receptor in mouse cerebellar cortex]. PG - 359-369 AB - Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABA(A) receptor was blocked by 100 micromol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of alpha2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The alpha2-AR agonist, UK14304, also increased the frequency of SS. The beta-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABA(A) receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating alpha2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission. FAU - Zhang, Xu-Dong AU - Zhang XD AD - Brain Science Research Center of Yanbian University, Yanji 133002, China. AD - Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China. FAU - Wang, Li-Fei AU - Wang LF AD - Department of Basic Medicine, College of Medicine, Changchun Sci-Tech University, Changchun 130600, China. FAU - Xuan, Fang-Ling AU - Xuan FL AD - Brain Science Research Center of Yanbian University, Yanji 133002, China. AD - Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China. FAU - Qiu, De-Lai AU - Qiu DL AD - Brain Science Research Center of Yanbian University, Yanji 133002, China. AD - Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China. FAU - Zhang, Bin-Bin AU - Zhang BB AD - Brain Science Research Center of Yanbian University, Yanji 133002, China. AD - Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China. bbZhang@ybu.edu.cn. FAU - Chu, Chun-Ping AU - Chu CP AD - Brain Science Research Center of Yanbian University, Yanji 133002, China. AD - Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China. cpchu@ybu.edu.cn. LA - chi PT - Journal Article PL - China TA - Sheng Li Xue Bao JT - Sheng li xue bao : [Acta physiologica Sinica] JID - 20730130R RN - 0 (Receptors, Adrenergic, alpha-2) RN - 0 (Receptors, GABA-A) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Action Potentials/physiology MH - Animals MH - Cerebellar Cortex/metabolism MH - Cerebellum/metabolism MH - Mice MH - *Norepinephrine/pharmacology MH - *Purkinje Cells/metabolism MH - Receptors, Adrenergic, alpha-2/metabolism MH - Receptors, GABA-A/metabolism EDAT- 2022/07/01 06:00 MHDA- 2022/07/02 06:00 CRDT- 2022/06/30 05:03 PHST- 2022/06/30 05:03 [entrez] PHST- 2022/07/01 06:00 [pubmed] PHST- 2022/07/02 06:00 [medline] PST - ppublish SO - Sheng Li Xue Bao. 2022 Jun 25;74(3):359-369.