Study of the mechanisms that regulate the activity of orexin-producing neuron.

食欲素在发作性睡病中的意义表明食欲素在正常调节和维持警觉状态中的重要性。食欲素神经元从LHA投射到脑干中的单胺能和胆碱能核，以调节睡眠/觉醒状态以及进食。食欲素神经元的活性受葡萄糖和瘦素的抑制，而受ghrelin的刺激。根据先前的报告，前原食欲素mRNA的上调禁食，这一观察表明，食欲素神经元感觉动物的营养状态，通过监测体液因子，如瘦素和葡萄糖。我们还发现食欲素神经元被5-羟色胺和去甲肾上腺素抑制，而被乙酰胆碱兴奋。我们最近发现，食欲素神经元受多个特定的大脑区域的神经支配，这些区域参与睡眠/觉醒状态的调节。本研究揭示了食欲素神经网络确保了POA睡眠活性神经元和单胺能神经元之间的“翻转“机制。因此，食欲素神经元与下丘脑摄食途径和单胺能/胆碱能中心具有功能性相互作用，并提供外周能量平衡与协调睡眠/觉醒和动机行为（如寻找食物）的CNS机制之间的关键联系。

The implication of orexin in narcolepsy suggests the importance of orexin in the normal regulation and maintenance of vigilance states. Orexin neurons project from the LHA to the monoaminergic and cholinergic nuclei in the brainstem to regulate sleep/wakefulness states as well as feeding. The activity of orexin neurons is inhibited by glucose and leptin, and stimulated by ghrelin. In accordance with the previous report that prepro-orexin mRNA is up-regulated by fasting, this observation suggests that orexin neurons sense the animal's nutritional state by monitoring humoral factors such as leptin and glucose. We also found that orexin neurons are inhibited by serotonin and noradrenaline, while excited by acetylcholine. We recently found that orexin neurons are innervated by multiple specific brain regions implicated in the regulation of sleep/wakefulness states. This study revealed that orexin neural network ensures"flip-flop"mechanisms between the POA sleep-active neurons and monoaminergic neurons. Thus, orexin neurons have functional interactions with hypothalamic feeding pathways and monoaminergic/cholinergic centers, and provide a critical link between peripheral energy balance and the CNS mechanisms that coordinate sleep/wakefulness and motivated behavior such as food seeking.