Xi M-C, Chase M H
WebSciences International, 1251 Westwood Boulevard, Los Angeles, CA 90024, USA.
Neuroscience. 2006 Jun 19;140(1):335-42. doi: 10.1016/j.neuroscience.2006.01.032. Epub 2006 Mar 14.
Hypocretinergic (orexinergic) neurons in the hypothalamus project to the nucleus pontis oralis, a nucleus which plays a crucial role in the generation of active (rapid eye movement) sleep. We recently reported that the microinjection of hypocretin into the nucleus pontis oralis of chronically-instrumented, unanesthetized cats induces a behavioral state that is comparable to naturally-occurring active sleep. The present study examined the intracellular signaling pathways underlying the active sleep-inducing effects of hypocretin. Accordingly, hypocretin-1, a protein kinase C inhibitor and a protein kinase A inhibitor were injected into the nucleus pontis oralis in selected combinations in order to determine their effects on sleep and waking states of chronically instrumented, unanesthetized cats. Microinjections of hypocretin-1 into the nucleus pontis oralis elicited active sleep with a short latency. However, a pre-injection of bisindolylmaleimide-I, a protein kinase C-specific inhibitor, completely blocked the active sleep-inducing effects of hypocretin-1. The combined injection of bisindolylmaleimide-I and hypocretin-1 significantly increased the latency to active sleep induced by hypocretin-1; it also abolished the increase in the time spent in active sleep induced by hypocretin-1. On the other hand, the injection of 2'5'-dideoxyadenosine, an adenylyl cyclase inhibitor, did not block the occurrence of active sleep by hypocretin-1. We conclude that the active sleep-inducing effect of hypocretin in the nucleus pontis oralis is mediated by intracellular signaling pathways that act via G-protein stimulation of protein kinase C.
下丘脑的促食欲素能（食欲素能）神经元投射到脑桥嘴侧核，该核在快速眼动睡眠的产生中起关键作用。我们最近报道，向长期植入仪器、未麻醉的猫的脑桥嘴侧核微量注射促食欲素会诱导出一种行为状态，这种状态与自然发生的快速眼动睡眠相当。本研究考察了促食欲素诱导快速眼动睡眠效应背后的细胞内信号通路。因此，将促食欲素 -1、一种蛋白激酶C抑制剂和一种蛋白激酶A抑制剂以选定的组合注射到脑桥嘴侧核中，以确定它们对长期植入仪器、未麻醉的猫的睡眠和清醒状态的影响。向脑桥嘴侧核微量注射促食欲素 -1会以较短潜伏期诱发快速眼动睡眠。然而，预先注射蛋白激酶C特异性抑制剂双吲哚马来酰亚胺 -I完全阻断了促食欲素 -1诱导快速眼动睡眠的效应。双吲哚马来酰亚胺 -I和促食欲素 -1联合注射显著延长了促食欲素 -1诱导快速眼动睡眠的潜伏期；它还消除了促食欲素 -1诱导的快速眼动睡眠时间增加。另一方面，注射腺苷酸环化酶抑制剂2'5'-二脱氧腺苷并没有阻断促食欲素 -1诱发快速眼动睡眠的发生。我们得出结论，促食欲素在脑桥嘴侧核诱导快速眼动睡眠的效应是由通过G蛋白刺激蛋白激酶C起作用的细胞内信号通路介导的。
