Format

Send to

Choose Destination
Mol Neurobiol. 2016 Mar;53(2):1386-1401. doi: 10.1007/s12035-015-9096-3. Epub 2015 Jan 30.

Selective Modulation of Histaminergic Inputs on Projection Neurons of Cerebellum Rapidly Promotes Motor Coordination via HCN Channels.

Author information

1
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.
2
Department of Physiology, Third Military Medical University, Chongqing, 400038, China.
3
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
4
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.
5
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.

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.

KEYWORDS:

Cerebellar nuclei; HCN channel; Histamine; Histamine H2 receptor; Motor control; Projection neurons

PMID:
25633097
DOI:
10.1007/s12035-015-9096-3
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center