Selective modulation of histaminergic inputs on projection neurons of cerebellum rapidly promotes motor coordination via HCN channels

J Zhang, QX Zhuang, B Li, GY Wu, WH Yung… - Molecular …, 2016 - Springer
J Zhang, QX Zhuang, B Li, GY Wu, WH Yung, JN Zhu, JJ Wang
Molecular neurobiology, 2016Springer
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 …
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.
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