Orexin A and orexin B are newly discovered peptides synthesized exclusively within the hypothalamus, The orexinergic fibers widely project to various regions in the brain including the cerebellum, an important subcortical center for motor control.As we reported previously, orexin A and orexin B excite cerebellar interpositus nucleus (IN) neurons via a direct postsynaptic action.In this study, the underlying ionic mechanisms and their physiological function have been further clarified.Immunostaining results showed that both orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) are presented in the rat cerebellar IN.Whole cell patch-clamp recordings from cerebellar slices showed that orexin A and orexin B selectively excited projection neurons (43/47, 91.5%) instead ofinterneurons (n =5) within the IN with a dose-dependent manner.The orexin-induced excitatory responses maintained in the presence of 0.3 μM tetrodotoxin, suggesting the actions of the peptides on IN neurons are postsynaptic.KB-R7943 and Ba2+, selective blockers for Na+-Ca2+ exchangers and inward rectifier K+ channels respectively, together totally blocked the orexin A-elicited inward current, suggesting that orexin A excites the IN projection neurons via both activation of Na+-Ca2+ exchangers and closure of inward rectifier K+ channels.Furthermore, bilaterally microinjection of orexin A into the IN significantly increased the rat exploratory behaviors in an open field, shortened the duration of passage through the balance beam and prolonged the time of the rats on an accelerated rota-rod.These results demonstrate that the central orexinergic system arising from the hypothalamus may directly modulate the activities of IN projection neurons and participate in motor control through its modulation on final outputs of the spinocerebellum.