Neural mechanisms of REM sleep: circadian influence.

睡眠是一种基本的生物过程，几乎在所有动物中都存在。在睡眠的各个阶段中，快速眼动（REM）睡眠是独特的，因为大脑是活跃的，但身体完全睡着了，除了快速眼动。REM睡眠在睡眠期结束时达到峰值，并且已知这种每日节律由哺乳动物大脑的视交叉上核（SCN）中容纳的昼夜节律（~24小时）时钟内部驱动。我们最近发现，多唾液酸化神经细胞粘附分子（PSA NCAM），一种促进细胞间相互作用的分子，在大鼠REM睡眠的昼夜模式中起作用。具体来说，一种能够去除PSA的化合物可以消除睡眠后期快速眼动睡眠的正常增加。然而，给药途径会影响整个大脑。事实上，SCN含有大量的PSA NCAM。因此，作为下一步，我们将选择性地从SCN中去除PSA NCAM，并观察对REM睡眠模式的影响。睡眠研究者长期以来一直认为，快速眼动睡眠是由大脑下部快速眼动神经元和快速眼动神经元之间的相互作用调节的。虽然SCN时钟可能会影响这种开关，但没有直接的解剖学联系。我们以前确定了SCN与觉醒和NREM睡眠核团的间接解剖连接。我们将使用类似的解剖学方法来识别从SCN到REM开启和REM关闭神经元的任何间接通路。SCN被认为在白天（或夜晚）的不同时间促进睡眠和觉醒，并且不同的SCN神经元被认为影响不同的生理功能。使用定时c-Fos（一种神经元激活标记物），我们将检验这一假设，即促进REM睡眠的SCN神经元与促进觉醒的SCN神经元在位置和投射上不同。这三项使用行为、解剖学和神经生理学技术的互补研究将揭示哺乳动物昼夜节律钟如何控制REM睡眠的时间，以实现对周期性环境的最大适应性。

Sleep is a fundamental biological process identified in virtually in all species of animals. Of various stages of sleep, rapid eye movement (REM) sleep is unique in that the brain is active but the body is totally asleep except for rapid eye movements. REM sleep peaks towards the end of the sleep period, and this daily rhythm is known to be driven internally by the circadian (~24 hours) clock housed in the suprachiasmatic nucleus (SCN) of the brain in mammals. We have recently shown that polysialylated neural cell adhesion molecule (PSA NCAM), a molecule that promotes cell-to-cell interaction, plays a role in the diurnal pattern of REM sleep in rats. Specifically, a compound that removes PSA pharmacologically abolished the normal increase in REM sleep in late sleep phase. However, the route of administration was such that it would have affected the entire brain. The SCN, in fact, contains high amounts of PSA NCAM. As a next step, therefore, we will remove PSA NCAM selectively from the SCN and observe effects on REM sleep patterns. Sleep researchers have long thought that REM sleep is regulated by the interaction between REM-on and REM-off neurons in the lower part of the brain. Although the SCN clock presumably influences this on-off switch, there are no direct anatomical connections. We previously identified indirect anatomical connections of the SCN with wake and NREM sleep nuclei. We will use a similar anatomical approach to identify any indirect pathways from the SCN to REM-on and REM-off neurons. The SCN is thought to promote sleep and wake at different times of day (or night), and distinct SCN neurons are thought to influence different physiological functions. Using timed c-Fos (a neuronal activation marker), we will test the hypothesis that SCN neurons that promote REM sleep are different from those that promote wake in their location and projections. These three complementary studies using behavioural, anatomical and neurophysiological techniques will shed light on how the mammalian circadian clock controls the timing of REM sleep to achieve maximal adaptability to the periodic environment.