Department of Psychology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Neuroscience. 2010 Mar 31;166(3):739-51. doi: 10.1016/j.neuroscience.2010.01.014. Epub 2010 Jan 15.
Some procedures for stimulating arousal in the usual daily rest period (e.g., gentle handling, novel wheel-induced running) can phase shift circadian rhythms in Syrian hamsters, while other arousal procedures are ineffective (inescapable stress, caffeine, modafinil). The dorsal and median raphe nuclei (DRN, MnR) have been implicated in clock resetting by arousal and, in rats and mice, exhibit strong regionally specific responses to inescapable stress and anxiogenic drugs. To examine a possible role for the midbrain raphe nuclei in the differential effects of arousal procedures on circadian rhythms, hamsters were aroused for 3 h in the mid-rest period by confinement to a novel running wheel, gentle handling (with minimal activity) or physical restraint (with intermittent, loud compressed air stimulation) and sacrificed immediately thereafter. Regional expression of c-fos and tryptophan hydroxylase (TrpOH) were quantified immunocytochemically in the DRN, MnR and locus coeruleus (LC). Neither gentle handling nor wheel running had a large impact on c-fos expression in these areas, although the manipulations were associated with a small increase in c-Fos in TrpOH-like and TrpOH-negative cells, respectively, in the caudal interfascicular DRN region. By contrast, restraint stress significantly increased c-Fos in both TrpOH-like and TrpOH-negative cells in the rostral DRN and LC. c-Fos-positive cells in the DRN did not express tyrosine hydroxylase. These results reveal regionally specific monoaminergic correlates of arousal-induced circadian clock resetting, and suggest a hypothesis that strong activation of some DRN and LC neurons by inescapable stress may oppose clock resetting in response to arousal during the daily sleep period. More generally, these results complement evidence from other rodent species for functional topographic organization of the DRN.
一些在通常的日常休息期间刺激觉醒的程序（例如，轻轻处理，新颖的轮诱导运行）可以使叙利亚仓鼠的昼夜节律相变，而其他觉醒程序则无效（无法逃避的压力，咖啡因，莫达非尼）。背侧和中缝核（DRN，MnR）已被牵连到通过觉醒重置时钟，并且在大鼠和小鼠中，对无法逃避的压力和焦虑药物表现出强烈的区域特异性反应。为了研究中脑缝核在觉醒程序对昼夜节律的不同影响中的可能作用，在中rest期将仓鼠限制在新颖的跑步轮中，轻轻处理（活动最少）或物理束缚（间歇性，响亮的压缩空气刺激）3 小时以唤醒，并立即处死。使用免疫细胞化学方法在 DRN，MnR 和蓝斑核（LC）中定量测定 c-fos 和色氨酸羟化酶（TrpOH）的区域表达。尽管这些操作分别与尾侧隔区 DRN 区域中分别与 TrpOH 样和 TrpOH 阴性细胞中的 c-Fos 小幅度增加相关，但轻柔处理或轮跑对这些区域中的 c-fos 表达没有很大影响。相比之下，束缚应激显着增加了 DRN 和 LC 中 TrpOH 样和 TrpOH 阴性细胞中的 c-Fos。 DRN 中的 c-Fos 阳性细胞不表达酪氨酸羟化酶。这些结果揭示了与觉醒诱导的生物钟重置相关的区域特异性单胺能相关性，并提出了一个假设，即无法逃避的压力对某些 DRN 和 LC 神经元的强烈激活可能会反对在日常睡眠期间对觉醒的时钟重置。更一般地说，这些结果补充了来自其他啮齿动物物种的证据，证明了 DRN 的功能拓扑组织。
