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Orexin, released from the hypothalamus, has been implicated in various basic non-somatic functions including feeding, the sleep-wakefulness cycle, emotion, and cognition. However, the role of orexin in somatic motor control is still little known. Here, using whole-cell patch clamp recording and immunostaining, we investigated the effect and the underlying receptor mechanism of orexin-A on neurons in the globus pallidus internus (GPi), a critical structure in the basal ganglia and an effective target for deep brain stimulation therapy. Our results showed that orexin-A induced direct postsynaptic excitation of GPi neurons in a concentration-dependent manner. The orexin-A-induced excitation was mediated via co-activation of both OX1 and OX2 receptors. Furthermore, the immunostaining results showed that OX1 and OX2 receptors were co-localized in the same GPi neurons. These results suggest that the central orexinergic system actively modulates the motor functions of the basal ganglia via direct innervation on GPi neurons and presumably participates in somatic-non-somatic integration.

Orexin Directly Enhances the Excitability of Globus Pallidus Internus Neurons in Rat by Co-activating OX1 and OX2 Receptors