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Noradrenaline modulates the spontaneous firing activities of Purkinje cells via α2-adrenergic receptor in mouse cerebellar cortex

ZHANG Xu-Dong^1,2, WANG Li-Fei³, XUAN Fang-Ling^1,2, QIU De-Lai^1,2, ZHANG Bin-Bin^1,2,*, CHU Chun-Ping^1,2

¹Brain Science Research Center of Yanbian University, Yanji 133002, China；²Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China ；³Department of Basic Medicine, College of Medicine, Changchun Sci-Tech University, Changchun 130600, China

Abstract

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. GABAA receptor was blocked by 100 µmol/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 α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABAA receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-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.

Key words: Noradrenaline; simple spike; complex spike; cerebellar Purkinje cell; GABAA receptor; adrenergic receptor

Received: 　　Accepted:

Corresponding author: 张斌斌　　E-mail: bbZhang@ybu.edu.cn

DOI: 10.13294/j.aps.2022.0034

Citing This Article：

ZHANG Xu-Dong, WANG Li-Fei, XUAN Fang-Ling, QIU De-Lai, ZHANG Bin-Bin, CHU Chun-Ping. Noradrenaline modulates the spontaneous firing activities of Purkinje cells via α2-adrenergic receptor in mouse cerebellar cortex. Acta Physiol Sin 2022; 74 (3): 359-369 (in Chinese with English abstract).