Molecular Neurobiology

, Volume 53, Issue 2, pp 1386–1401 | Cite as

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



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.


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



We thank Dr Rob Leurs (VU University Amsterdam, Amsterdam, the Netherlands) for his generous gifts of histamine H4 receptor agonist and antagonist. The work was supported by grants 31070959, 31071021, 31171050, 31330033, 91332124, 31471112 and NSFC/RGC Joint Research Scheme 31461163001 from the National Natural Science Foundation of China; SRFDP/RGC ERG grant 20130091140003 and NCET Program from the State Educational Ministry of China; grants BK2011014 and BK20140599 from the Natural Science Foundation of Jiangsu Province, China; and grant 2013T60520 from the China Postdoctoral Science Foundation.

Conflict of Interest


Supplementary material

12035_2015_9096_MOESM1_ESM.doc (2.3 mb)
Fig. S1 (DOC 2322 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life SciencesNanjing UniversityNanjingChina
  2. 2.School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong KongHong KongChina
  3. 3.Department of PhysiologyThird Military Medical UniversityChongqingChina

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