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.
The central noradrenergic system, originating mainly from the locus coeruleus in the brainstem, plays an important role in many physiological functions, including arousal and attention, learning and memory, anxiety, and nociception. However, little is known about the roles of norepinephrine (NE) in somatic motor control. Therefore, using extracellular recordings on rat brainstem slices and quantitative real-time RT-PCR, we investigate the effect and mechanisms of NE on neuronal activity in the inferior vestibular nucleus (IVN), the largest nucleus in the vestibular nuclear complex, which holds an important position in integration of information signals controlling body posture. Here, we report that NE elicits an excitatory response on IVN neurons in a concentration-dependent manner. Activation of α1 - and β2 -adrenergic receptors (ARs) induces an increase in firing rate of IVN neurons, whereas activation of α2 -ARs evokes a decrease in firing rate of IVN neurons. Therefore, the excitation induced by NE on IVN neurons is a summation of the excitatory components mediated by coactivation of α1 - and β2 -ARs and the inhibitory component induced by α2 -ARs. Accordingly, α1 -, α2 -, and β2 -AR mRNAs are expressed in the IVN. Although β1 -AR mRNAs are also detected, they are not involved in the direct electrophysiological effect of NE on IVN neurons. All these results demonstrate that NE directly regulates the activity of IVN neurons via α1 -, α2 -, and β2 -ARs and suggest that the central noradrenergic system may actively participate in IVN-mediated vestibular reflexes and postural control. © 2016 Wiley Periodicals, Inc.
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