The cerebellar fastigial nucleus (FN) holds an important role in motor control and regulating body balance.Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar histaminergic fibers arose from the tuberomammillary nucleus of the hypothalamus.However,the functional role of histaminergic projection on 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.Seventy-seven cells were recorded from 56 cerebellar slices,and vast majority of the cells responded to histamine stimulation with an excitatory response (84.4%,65/77).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 =20) or chlorpheniramine (n =10),but was effectively suppressed by ranitidine (n =15),a highly selective histamine H2 receptor antagonist.