Orexins Excite Neurons of the Rat Cerebellar Nucleus Interpositus Via Orexin 2 Receptors In Vitro
Orexins Excite Neurons of the Rat Cerebellar Nucleus Interpositus Via Orexin 2 Receptors In Vitro
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DOI：
10.1007/s12311-009-0146-0
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发表时间：
2010-03
期刊：
影响因子：
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通讯作者：
Lei Yu;Xiao-Yang Zhang;Jun Zhang;Jing-Ning Zhu;Jian-jun Wang
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作者：
Lei Yu;Xiao-Yang Zhang;Jun Zhang;Jing-Ning Zhu;Jian-jun Wang
食欲素是新近发现的一种下丘脑神经肽，参与摄食行为、睡眠-觉醒周期、伤害感受、成瘾、情绪以及嗜睡症的调节。然而，对食欲素在运动控制中的作用知之甚少。因此，本研究旨在探讨食欲素对小脑神经元活动的影响，小脑是一个重要的皮质下运动控制中心。在这项研究中，用食欲素A（100 nM-1 μM）或食欲素B（100 nM-1 μM）灌注切片均在大鼠小脑间位核（IN）中产生浓度依赖性兴奋反应（96/143，67.1%）。此外，由食欲素A和B诱导的兴奋均未被低Ca 2 +/高Mg 2+培养基（n= 8）阻断，支持肽的直接突触后作用。高选择性食欲素1受体拮抗剂SB-334867不能阻断小脑IN神经元对食欲素的兴奋性反应（n= 22），但高选择性食欲素2受体（OX 2 R）激动剂[Ala 11，D-Leu 15]食欲素B可模拟食欲素对小脑神经元的兴奋性反应（n= 18）。这些结果表明，orexins兴奋小脑IN神经元通过OX 2 R，并表明中枢orexinergic神经系统可能积极参与运动控制，通过其调制的最终输出之一的脊髓小脑。
Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep–wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM–1 μM) or orexin B (100 nM–1 μM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca2+/high-Mg2+medium (n= 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n= 22), but [Ala11, D-Leu15] orexin B, a highly selective orexin 2 receptor (OX2R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n= 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX2R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.