Fos expression in orexin neurons varies with behavioral state
Fos expression in orexin neurons varies with behavioral state
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DOI：
10.1523/jneurosci.21-05-01656.2001
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发表时间：
2001-03-01
影响因子：
5.3
通讯作者：
Scammell, TE
中科院分区：
文献类型：
--
作者：
Estabrooke, IV;McCarthy, MT;Scammell, TE
神经肽增食欲素(也称为下丘脑素)被认为在睡眠-觉醒行为的调节中发挥关键作用。缺乏食欲素会导致嗜睡症，其特征是难以维持清醒状态，并干扰快速眼动(REM)睡眠或类似REM睡眠的现象进入清醒状态。食欲素神经元大量支配促进觉醒和抑制快速眼动睡眠的许多胺能核。我们假设食欲素神经元在清醒时相对活跃，在睡眠时相对不活跃。为了确定增食欲素神经元的活动模式，我们记录了不同条件下的睡眠-觉醒行为、体温和运动活动，并采用双标记免疫组织化学方法检测了穹隆周围区增食欲素神经元中Fos的表达。在维持12小时光/暗周期的大鼠中，夜间有更多的增食欲素神经元有Fos免疫反应阳性核；而在持续黑暗中的动物，这种激活仍然发生在主观的夜晚。睡眠剥夺或甲基苯丙胺治疗也增加了增食欲素神经元中Fos的表达。在每个实验中，食欲素神经元的Fos表达与觉醒时间呈正相关，与之前2小时的非快速眼动睡眠和快速眼动睡眠呈负相关。结合以前的工作，这些结果表明，激活增食欲素神经元可能有助于促进或维持觉醒。相反，食欲素神经元的相对不活跃可能允许睡眠的表达。
The neuropeptide orexin (also known as hypocretin) is hypothesized to play a critical role in the regulation of sleep-wake behavior. Lack of orexin produces narcolepsy, which is characterized by poor maintenance of wakefulness and intrusions of rapid eye movement (REM) sleep or REM sleep-like phenomena into wakefulness. Orexin neurons heavily innervate many aminergic nuclei that promote wakefulness and inhibit REM sleep. We hypothesized that orexin neurons should be relatively active during wakefulness and inactive during sleep. To determine the pattern of activity of orexin neurons, we recorded sleep-wake behavior, body temperature, and locomotor activity under various conditions and used double-label immunohistochemistry to measure the expression of Fos in orexin neurons of the perifornical region. In rats maintained on a 12 hr light/ dark cycle, more orexin neurons had Fos immunoreactive nuclei during the night period; in animals housed in constant darkness, this activation still occurred during the subjective night. Sleep deprivation or treatment with methamphetamine also increased Fos expression in orexin neurons. In each of these experiments, Fos expression in orexin neurons correlated positively with the amount of wakefulness and correlated negatively with the amounts of non-REM and REM sleep during the preceding 2 hr. In combination with previous work, these results suggest that activation of orexin neurons may contribute to the promotion or maintenance of wakefulness. Conversely, relative inactivity of orexin neurons may allow the expression of sleep.