title: Selective Modulation of Histaminergic Inputs on Projection Neurons of Cerebellum Rapidly Promotes Motor Coordination via HCN Channels.
abstract: Insights into function of central histaminergic system, a general modulator originating from the hypothalamus for whole brain activity, in motor control are critical for understanding the mechanism underlying somatic-nonsomatic integration. Here, we show a novel selective role of histamine in the cerebellar nuclei, the final integrative center and output of the cerebellum. Histamine depolarizes projection neurons but not interneurons in the cerebellar nuclei via the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to histamine H2 receptors, which are exclusively expressed on glutamatergic and glycinergic projection neurons. Furthermore, blockage of HCN channels to block endogenous histaminergic afferent inputs in the cerebellar nuclei significantly attenuates motor balance and coordination. Therefore, through directly and quickly modulation on projection neurons but not interneurons in the cerebellar nuclei, central histaminergic system may act as a critical biasing force to not only promptly regulate ongoing movement but also realize a rapid integration of somatic and nonsomatic response.
authors: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China.|Department of Physiology, Third Military Medical University, Chongqing, 400038, China.
authors: Jun
authors: J
authors: Zhang
authors: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China.
authors: Qian-Xing
authors: QX
authors: Zhuang
authors: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China.
authors: Bin
authors: B
authors: Li
authors: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China.
authors: Guan-Yi
authors: GY
authors: Wu
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Wing-Ho
authors: WH
authors: Yung
authors: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China. jnzhu@nju.edu.cn.
authors: Jing-Ning
authors: JN
authors: Zhu
authors: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China. jjwang@nju.edu.cn.
authors: Jian-Jun
authors: JJ
authors: Wang
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D007395:Interneurons / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011970:Receptors, Histamine H2 / Q000378:metabolism
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D011970:Receptors, Histamine H2; D018698:Glutamic Acid; D006632:Histamine
keywords: Cerebellar nuclei; HCN channel; Histamine; Histamine H2 receptor; Motor control; Projection neurons
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