Karatsoreos Ilia N, Yan Lily, LeSauter Joseph, Silver Rae
Department of Psychology, Columbia University, New York, New York 10027, USA.
J Neurosci. 2004 Jan 7;24(1):68-75. doi: 10.1523/JNEUROSCI.1666-03.2004.
The suprachiasmatic nucleus (SCN) of the hypothalamus is the neural locus of the circadian clock. To explore the organization of the SCN, two strains of transgenic mice, each bearing a jellyfish green fluorescent protein (GFP) reporter, were used. In one, GFP was driven by the promoter region of the mouse Period1 gene (mPer1) (Per1::GFP mouse), whereas in the other, GFP was inserted in the promoter region of calbindin-D(28K)-bacterial artificial chromosome (CalB::GFP mouse). In the latter mouse, GFP-containing SCN cells are immunopositive for gastrin-releasing peptide. In both mouse lines, light-induced Per1 mRNA and Fos are localized to the SCN subregion containing gastrin-releasing peptide. Double-label immunohistochemistry reveals that most gastrin-releasing peptide cells (approximately 70%) contain Fos after a brief light pulse. To determine the properties of SCN cells in this light-responsive region, we examined the expression of rhythmic Period genes and proteins. Gastrin-releasing peptide-containing cells do not express detectable rhythms in these key components of the molecular circadian clock. The results support the view that the mammalian SCN is composed of functionally distinct cell groups, of which some are light induced and others are rhythmic with respect to clock gene expression. Furthermore, the findings suggest that gastrin-releasing peptide is a potential mediator of intercellular communication between light-induced and oscillator cells within the SCN.
下丘脑的视交叉上核(SCN)是昼夜节律钟的神经位点。为了探究SCN的组织结构,使用了两种转基因小鼠品系,每种都携带水母绿色荧光蛋白(GFP)报告基因。在一种品系中,GFP由小鼠周期蛋白1基因(mPer1)的启动子区域驱动(Per1::GFP小鼠),而在另一种品系中,GFP插入到钙结合蛋白-D(28K)-细菌人工染色体的启动子区域(CalB::GFP小鼠)。在后者的小鼠中,含有GFP的SCN细胞对胃泌素释放肽呈免疫阳性。在这两种小鼠品系中,光诱导的Per1 mRNA和Fos定位于含有胃泌素释放肽的SCN亚区域。双重标记免疫组织化学显示,在短暂光脉冲后,大多数胃泌素释放肽细胞(约70%)含有Fos。为了确定这个光反应区域中SCN细胞的特性,我们检测了节律性周期基因和蛋白质的表达。含有胃泌素释放肽的细胞在分子昼夜节律钟的这些关键成分中不表达可检测到的节律。这些结果支持了这样一种观点,即哺乳动物的SCN由功能不同的细胞群组成,其中一些细胞群是光诱导的,而另一些细胞群在时钟基因表达方面具有节律性。此外,这些发现表明胃泌素释放肽是SCN内光诱导细胞和振荡器细胞之间细胞间通讯的潜在介质。