Zhang Jun, Zhuang Qian-Xing, Li Bin, Wu Guan-Yi, Yung Wing-Ho, Zhu Jing-Ning, Wang Jian-Jun
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.
Mol Neurobiol. 2016 Mar;53(2):1386-1401. doi: 10.1007/s12035-015-9096-3. Epub 2015 Jan 30.
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.
深入了解中枢组胺能系统的功能对于理解躯体-非躯体整合的潜在机制至关重要。中枢组胺能系统是一种起源于下丘脑、调节全脑活动的通用调节因子。在这里，我们展示了组胺在小脑核团中的一种新的选择性作用，小脑核团是小脑的最终整合中心和输出部位。组胺通过与组胺H2受体偶联的超极化激活环核苷酸门控（HCN）通道使小脑核团中的投射神经元去极化，但不影响中间神经元，这些通道仅在谷氨酸能和甘氨酸能投射神经元上表达。此外，阻断HCN通道以阻断小脑核团中内源性组胺能传入输入会显著减弱运动平衡和协调性。因此，通过直接且快速地调节小脑核团中的投射神经元而非中间神经元，中枢组胺能系统可能作为一种关键的偏置力，不仅能迅速调节正在进行的运动，还能实现躯体和非躯体反应的快速整合。
