Excitatory effects of hypocretin-1 (orexin-A) in the trigeminal motor nucleus are reversed by NMDA antagonism
Excitatory effects of hypocretin-1 (orexin-A) in the trigeminal motor nucleus are reversed by NMDA antagonism
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DOI：
10.1152/jn.00968.2002
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发表时间：
2003-05-01
影响因子：
2.5
通讯作者：
Siegel, JM
中科院分区：
文献类型：
--
作者：
Peever, JH;Lai, YY;Siegel, JM
下丘脑泌素-1和2（Hypocretin-1 and-2，Hcrt-1 and-2，orexin-A and -B）是新近发现的由下丘脑神经元合成的神经肽。Hcrt系统的缺陷是睡眠障碍发作性睡病的基础，发作性睡病的特征是睡眠片段化和被称为cataepsy的肌张力的不自主丧失。Hcrt神经元投射到多个脑区，包括颅和脊髓运动核。体外研究表明，Hcrt的应用可以调节突触前谷氨酸的释放。总之，这些观察结果表明，Hcrt可以影响运动输出，并可能涉及到海马能过程。我们通过将Hcrt-1和-2应用于三叉神经运动核来确定这些配体是否改变咬肌活动，并通过用N-甲基-D-天冬氨酸（NMDA）拮抗剂预处理三叉神经运动核来确定Hcrt信号的转导是否涉及到神经元通路来解决去大脑猫中的这些问题。我们发现，Hcrt-1和-2微量注射到三叉神经运动核增加同侧咬肌肌张力的剂量依赖性的方式。我们还发现，Hcrt应用到舌下神经运动核增加颏舌肌的活动。预处理与NMDA拮抗剂（D-（-）-2-氨基-膦酰基-戊酸）取消了兴奋性反应的咬肌Hcrt-1的应用程序，然而，预处理与麦角新碱，5-羟色胺拮抗剂没有影响。这些研究首次证明Hcrt引起运动神经元的兴奋，并且这种反应需要功能性NMDA受体。我们认为，Hcrt调节运动控制过程，这种调节是由三叉神经运动核谷氨酸释放介导的。
Hypocretin-1 and -2 (Hcrt-1 and -2, also called orexin-A and -B) are newly identified neuropeptides synthesized by hypothalamic neurons. Defects in the Hcrt system underlie the sleep disorder narcolepsy, which is characterized by sleep fragmentation and the involuntary loss of muscle tone called cataplexy. Hcrt neurons project to multiple brain regions including cranial and spinal motor nuclei. In vitro studies suggest that Hcrt application can modulate presynaptic glutamate release. Together these observations suggest that Hcrt can affect motor output and that glutamatergic processes may be involved. We addressed these issues in decerebrate cats by applying Hcrt-1 and -2 into the trigeminal motor nucleus to determine whether these ligands alter masseter muscle activity and by pretreating the trigeminal motor nucleus with a N-methyl-D-aspartate (NMDA) antagonist to determine if glutamatergic pathways are involved in the transduction of the Hcrt signal. We found that Hcrt-1 and -2 microinjections into the trigeminal motor nucleus increased ipsilateral masseter muscle tone in a dose-dependent manner. We also found that Hcrt application into the hypoglossal motor nucleus increases genioglossus muscle activity. Pretreatment with a NMDA antagonist (D-(-)-2-amino-phosphono-valeric acid) abolished the excitatory response of the masseter muscle to Hcrt-1 application; however, pretreatment with methysergide, a serotonin antagonist had no effect. These studies are the first to demonstrate that Hcrt causes the excitation of motoneurons and that functional NMDA receptors are required for this response. We suggest that Hcrt regulates motor control processes and that this regulation is mediated by glutamate release in the trigeminal motor nucleus.