Granados-Fuentes Daniel, Prolo Laura M, Abraham Ute, Herzog Erik D
Department of Biology, Washington University, St. Louis, Missouri 63130-4899, USA.
J Neurosci. 2004 Jan 21;24(3):615-9. doi: 10.1523/JNEUROSCI.4002-03.2004.
The suprachiasmatic nucleus (SCN) of the hypothalamus has been termed the master circadian pacemaker of mammals. Recent discoveries of damped circadian oscillators in other tissues have led to the hypothesis that the SCN synchronizes and sustains daily rhythms in these tissues. We studied the effects of constant lighting (LL) and of SCN lesions on behavioral rhythmicity and Period 1 (Per1) gene activity in the SCN and olfactory bulb (OB). We found that LL had similar effects on cyclic locomotor and feeding behaviors and Per1 expression in the SCN but had no effect on rhythmic Period 1 expression in the OB. LL lengthened the period of locomotor and SCN rhythms by approximately 1.6 hr. After 2 weeks in LL, nearly 35% of rats lost behavioral rhythmicity. Of these, 90% showed no rhythm in Per1-driven expression in their SCN. Returning the animals to constant darkness rapidly restored their daily cycles of running wheel activity and gene expression in the SCN. In contrast, the OB remained rhythmic with no significant change in period, even when cultured from animals that had been behaviorally arrhythmic for 1 month. Similarly, we found that lesions of the SCN abolished circadian rhythms in behavior but not in the OB. Together, these results suggest that LL causes the SCN to lose circadian rhythmicity and its ability to coordinate daily locomotor and feeding rhythms. The SCN, however, is not required to sustain all rhythms because the OB continues to oscillate in vivo when the SCN is arrhythmic or ablated.
下丘脑的视交叉上核(SCN)被称为哺乳动物的主昼夜节律起搏器。最近在其他组织中发现了衰减的昼夜节律振荡器,这引发了一种假说,即SCN使这些组织中的日常节律同步并维持。我们研究了持续光照(LL)和SCN损伤对SCN和嗅球(OB)中行为节律性和周期1(Per1)基因活性的影响。我们发现,LL对SCN中的周期性运动和进食行为以及Per1表达有类似影响,但对OB中节律性的周期1表达没有影响。LL使运动和SCN节律的周期延长了约1.6小时。在LL环境中饲养2周后,近35%的大鼠失去了行为节律性。其中,90%的大鼠SCN中Per1驱动的表达没有节律。将动物放回持续黑暗环境中,它们的跑步轮活动和SCN中的基因表达的日常周期迅速恢复。相比之下,即使是从已经行为性心律失常1个月的动物中培养出来的OB,仍然保持节律性,周期没有明显变化。同样,我们发现SCN损伤消除了行为中的昼夜节律,但没有消除OB中的昼夜节律。这些结果共同表明,LL导致SCN失去昼夜节律性及其协调日常运动和进食节律的能力。然而,维持所有节律并不需要SCN,因为当SCN心律失常或被切除时,OB在体内仍继续振荡。