| Paper 1 Orexin A excites neurons of globus pallidus internal segment in rats by activation of OX1R and OX2R receptorsOrexin is a hypothalamic neuropeptide found in 1998. Originally, orexin was considered to be a neurotransmitter that centrally stimulates food intake, but it sooner became evident that orexin is involved in many basic physiological processes including energy homeostasis, sleep-awake cycle, nociception, food and drug addiction, as well as emotions. Especially, it’s reported that orexin is related to motor control:(1) Orexin deficiency in animals results in cataplexy, which is characterized by sudden loss of muscle tone; (2) In the process of movement, orexinergic neurons are extremely active and release more orexin; (3) The injection of orexin in the midbrain motor area of the decerebrate cats can motivate motion and promote muscle tone. Therefore, the mechanism of central orexinergic system on motor control remains to be further clarified.Globus pallidus internal segment (GPi), together with the substania nigra reticulate, constitutes the output nuclei of the basal ganglia. Clinically, it can effectively alleviate movement disorder of Parkinson’s disease to make deep brain stimulation in GPi. Although a lot of immunohistochemical studies showed that central orexinergic neurons innervate many subcortical motor control structures including GPi, the effect and downstream receptor mechanism of orexin on GPi neurons are still unclear.We investigated the effect of orexin A on GPi neuron activity by using the immunofluorescence histochemistry and whole-cell patch clamp recording on rat brain slices. Our results are as follows:(1) Orexin A excited GPi neurons in a concentration-dependent manner; (2) The excitatory effect of orexin A on GPi neurons was a direct postsynaptic action; (3) The orexin A-induced excitation was mediated by the co-activation of both OX1R and OX2R; (4) OX1R and OX2R were co-expressed in GPi neurons. All results suggest that central orexinergic system may actively modulate the motor initiation and motor control of basal ganglia via its direct modulation on GPi neurons.Paper 2 Excitatory effect of norepinephrine on neurons in the inferior vestibular nucleus and the underlying receptor mechanismCentral noradrenergic system, mainly originating from the locus coeruleus in brainstem, plays an important role in many physiological functions, including arousal and attention, learning and memory, anxiety and nociception. However, little is known about roles of norepinephrine (NE) in somatic motor control. Therefore, by using extracellular recordings on rat brainstem slices and qPCR, 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 that 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 co-activation 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 FVN neurons. All these results demonstrate that NE directly regulates the activity of FVN neurons via α1,α2-and β2-ARs, and suggest that the central noradrenergic system may actively participate in the IVN-mediated vestibular reflexes and postural control. |
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