Excitatory effect of histamine on neuronal activity of rat cerebellar fastigial nucleus in vitro  

作　　者：TANG Biao ZHANG Jun LI HongZhao ZHU JingNing WANG JianJun 

机构地区：[1]Department of Biological Science and Technology/State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China [2]Jiangsu Key Laboratory for Bioresource Technology, School of Life Sciences, Nanjing Normal University, Nanjing 210097, China

出　　处：《Chinese Science Bulletin》2007年第4期497-503,共7页

基　　金：Supported by the National Natural Science Foundation of China (Grant Nos. 30370462 and 30670671);the NSFC-RGC Joint Research Scheme of the National Natural Science Foundation of China (Grant No. 30318004);the State Education Ministry of China (Grant No. RFDP-20050284025);the Natural Science Foun-dation of Jiangsu Province, China (Grant No. BK2006713)

摘　　要：The cerebellar fastigial nucleus (FN) holds an important role in motor control and body balance. Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar histaminergic fibers. However, the functional role of histaminergic projection in cerebellar FN has never been established. In this study, we investigated the effect of histamine on neuronal firing of cerebellar FN by using slice preparations. Sixty-five FN cells were recorded from 47 cerebellar slices, and a vast majority of the cells responded to histamine stimulation with an excitatory response (58/65, 89.2%). Perfusing slices with low-Ca2+/high-Mg2+ medium did not block the histamine-induced excitation (n=10), supporting a direct postsynaptic action of histamine on the cells. Furthermore, the excitatory effect of histamine on FN neurons was not blocked by selective histamine H1 receptor antagonist triprolidine (n=15) or chlorpheniramine (n=10), but was effectively suppressed by ranitidine (n=15), a highly selective histamine H2 receptor antagonist. On the other hand, highly selective histamine H2 receptor agonist dimaprit (n=20) instead of histamine H1 receptor agonist 2-pyridylethylamine (n=16) mimicked the ex- citatory effect of histamine on FN neurons. The dimaprit-induced FN neuronal excitation was effectively antagonized by selective histamine H2 receptor antagonist ranitidine (n=13) but not influenced by se- lective histamine H1 receptor antagonist triprolidine (n=15). These results demonstrate that histamine excites cerebellar FN cells via the histamine H2 receptor mechanism and suggest that the hypotha- lamocerebellar histaminergic fibers may modulate cerebellar FN-mediated sensorimotor integration through their excitatory innervations on FN neurons.The cerebellar fastigial nucleus （FN） holds an important role in motor control and body balance. Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar hletaminergic fibers. However, the functional role of histaminergic projection in cerebellar FN has never been established. In this study, we investigated the effect of histamine on neuronal firing of cerebellar FN by using slice preparations. Sixty-five FN cells were recorded from 47 cerebellar slices, and a vast majority of the cells responded to histamine stimulation with an excitatory response （58/65, 89.2%）. Perfusing slices with low-Ca^2＋/high-Mg^2＋ medium did not block the histamine-induced excitation （n=10）, supporting a direct postsynaptic action of histamine on the cells. Furthermore, the excitatory effect of histamine on FN neurons was not blocked by selective histamine H1 receptor antagonist triprolidine （n=15） or chlorpheniramine （n=10）, but was effectively suppressed by ranitidine （n=15）, a highly selective histamine H2 receptor antagonist. On the other hand, highly selective histamine H2 receptor agonist dimaprit （n=20） instead of histamine HI receptor agonist 2-pyridylethylamine （n=16） mimicked the excitatory effect of histamine on FN neurons. The dimaprit-induced FN neuronal excitation was effectively antagonized by selective histamine H2 receptor antagonist ranitidine （n=13） but not influenced by selective histamine H1 receptor antagonist triprolidine （n=15）. These results demonstrate that histamine excites cerebellar FN cells via the histamine H2 receptor mechanism and suggest that the hypothalamocerebellar histaminergic fibers may modulate cerebellar FN-mediated sensorimotor integration through their excitatory innervations on FN neurons.

关 键 词：大鼠 小脑顶核 神经活动 组胺受体 兴奋作用 

分 类 号：Q426[生物学—神经生物学] R338.23[生物学—生理学]