Guido M E, de Guido L, Goguen D, Robertson H A, Rusak B
Department of Psychology, Life Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
Brain Res Mol Brain Res. 1999 Apr 20;67(2):247-57. doi: 10.1016/s0169-328x(99)00074-1.
Nocturnal light exposure induces immediate-early gene (IEG) expression in the hypothalamic suprachiasmatic nucleus (SCN) and causes phase shifts of activity rhythms in mammals. Some IEGs also show a circadian rhythm of expression in the SCN. While excitatory amino acids (EAAs) are known to be involved in mediating photic regulation of entrainment and gene expression, their involvement in spontaneous rhythms of gene expression has not been studied. We assessed the role of NMDA receptors in the expression of NGFI-A, junB and fosB mRNAs induced by light pulses of different intensities late in the night (Zeitgeber Time [ZT] 18). We also examined the spontaneous expression of junB mRNA near subjective dawn (ZT 0). Both dim (5 lx) and bright (100 lx) light pulses induced similar levels of expression of NGFI-A and junB in the SCN late in the night. fosB mRNA was strongly induced by bright light but was less sensitive to dim light. At ZT 18, dizocilpine (MK-801) (3 mg/kg, i.p. ), a non-competitive NMDA receptor antagonist, almost completely blocked light-evoked expression of IEG mRNAs in the ventral SCN but not in the dorsolateral region at a mid-caudal level using either light intensity. At ZT 0, MK-801 strongly reduced light-evoked expression of junB mRNA in both SCN subdivisions, but inhibited spontaneous expression significantly only in the dorsal region. NMDA receptors appear to play an important role in mediating photic input regulating IEG expression only in the ventral SCN at night. At dawn, however, NMDA receptors are involved in mediating photic effects in both parts of the SCN, as well as being involved in spontaneous activation of junB expression selectively in the dorsal SCN. These findings support the idea that the effects in the dorsolateral SCN of nocturnal light exposure are mediated by different mechanisms than those in other portions of the nucleus.
夜间光照会诱导下丘脑视交叉上核(SCN)中即刻早期基因(IEG)的表达,并导致哺乳动物活动节律的相位偏移。一些即刻早期基因在视交叉上核中也呈现出昼夜节律性表达。虽然已知兴奋性氨基酸(EAA)参与介导光对昼夜节律的调节和基因表达,但它们在基因表达的自发节律中的作用尚未得到研究。我们评估了NMDA受体在深夜(时间geber时间[ZT]18)不同强度光脉冲诱导的NGFI-A、junB和fosB mRNA表达中的作用。我们还检测了主观黎明(ZT 0)附近junB mRNA的自发表达。深夜时,昏暗(5勒克斯)和明亮(100勒克斯)的光脉冲在视交叉上核中诱导出相似水平的NGFI-A和junB表达。fosB mRNA受到强光强烈诱导,但对弱光不太敏感。在ZT 18时,非竞争性NMDA受体拮抗剂地佐环平(MK-801)(3毫克/千克,腹腔注射),几乎完全阻断了腹侧视交叉上核中光诱发的即刻早期基因mRNA表达,但在中尾水平的背外侧区域,无论使用何种光强度均未阻断。在ZT 0时,MK-801强烈降低了两个视交叉上核亚区中光诱发的junB mRNA表达,但仅在背侧区域显著抑制了自发表达。NMDA受体似乎仅在夜间腹侧视交叉上核中介导光输入调节即刻早期基因表达中起重要作用。然而,在黎明时,NMDA受体参与介导视交叉上核两部分的光效应,以及选择性地参与背侧视交叉上核中junB表达的自发激活。这些发现支持了这样一种观点,即夜间光照对视交叉上核背外侧区域的影响是由与该核其他部分不同的机制介导的。