Roles of orexins in regulation of sleep/wake states

我们已经确定了几个影响食欲素产生神经元活动的因素，包括加压素、神经降压素和促甲状腺激素释放激素（TRH）。我们还发现，产生食欲素的神经元表达孤儿受体，BRS-3，这可能也参与了食欲素神经元的调节。加压素激活食欲素神经元在调节小鼠自发活动中具有重要作用。这个系统似乎在缺水引起的过度运动活动中发挥作用，这是一种对脱水的反应，增加了在自然界中定位水的机会。我们还发现促甲状腺激素释放激素调节行为唤醒和交感神经流出，部分是通过食欲素系统。我们还分析了在增食欲素神经元上特异性缺失GABA_2基因的小鼠的体内和体外表型<B1>，并证明增食欲素神经元上的GABA_B受体在稳定和巩固睡眠/觉醒状态中是必不可少的。

We have identified several factors that influence activity of orexin-producing neurons, including vasopressin, neurotensin, and thyrotropin-releasing hormone (TRH). We also revealed that orexin-producing neurons express an orphan receptor, BRS-3, which might be also involved in the regulation of orexin neurons. The activation of orexin neurons by vasopressin has an important role in the regulation of spontaneous locomotor activity in mice. This system appears to play a role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature. We also found that thyrotropin-releasing hormone modulates behavioral arousal and sympathetic outflow, in part, through the orexin system. We also analyze the in vivo and in vitro phenotype of mice lacking the GABA_<B1> gene specifically in orexin neurons, and demonstrate that GABA_B receptors on orexin neurons are essential in stabilizing and consolidating sleep/wake states.