Neuronal mechanisms of active (rapid eye movement) sleep induced by microinjections of hypocretin into the nucleus pontis oralis of the cat

作者：Xi MC; Chase MH^*

来源：Neuroscience, 2006, 140(1): 335-342.

DOI：10.1016/j.neuroscience.2006.01.032

• REM sleep
• orexin
• protein kinase C
• protein kinase A
• brainstem
• cat

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-1, a protein kinase C-specific inhibitor, completely blocked the active sleep-inducing effects of hypocretin-1. The combined injection of bisindolylmaleimide-1 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.

• 出版日期2006