Cellular Organization of the Circadian Light Response

昼夜节律光反应的细胞组织

• 批准号: 6647102
• 负责人: Jennifer W Mitchell
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6647102
• 关键词: NMDA receptors; RNase protection assay; brain electrical activity; cell cell interaction; circadian rhythms; gene expression; genetic regulation; immunocytochemistry; laboratory rat; lighting; neural information processing; photobiology; suprachiasmatic nucleus

DESCRIPTION (provided by applicant): The suprachiasmatic nucleus (SCN) in the hypothalamus has been identified as a primary timekeeper of mammalian circadian rhythms, exhibiting a neuronal firing rate pattern near 24 h in length in the animals in an aperiodic environment. The neuronal rhythms of the SCN can be phase delayed in response to a pulse of light given in the early night, which correlates to a similar phase delay in the activity rhythms of rodents. Despite its central role as a circadian clock, the emerging picture of the SCN is one of internal heterogeneity. Little is known of how subregions contribute to the function of the SCN as a whole. Interestingly, in hamsters, a subset of cells within the SCN immunoreactive for a calcium binding protein, calbindin-D28k (CaBP), correlates with rhythm generation and seems to be particularly responsive to light stimulation. However, rats lack this distinct CaBP subregion. An analogous region may, instead, be a distinct subregion containing cells immunoreactive for calretinin (CN). The SCN retains its clock properties in vitro, exhibiting similar phase delays in response to the neurochemical signal of light, glutamate (GLU), during the early night. Downstream communication includes GLU binding to NMDA receptor, Ca2+ influx, nitric oxide (NO) production, and activation of Ca2+(I) via the ryanodine receptor (RyR). Light or GLU stimulation in the early night also up-regulates two clock genes, Per1 and Per2. This proposal will investigate the signaling pathway involved in light-induced up-regulation of Per1 and Per2 in early night. The specific aims are: 1) To test the hypothesis that the light-induced up-regulation in Per1 and Per2 is localized in specific subregions of the SCN, 2) To test the hypothesis that the GLU induced up-regulation of Per1 and Per2 in early night is signaled through the NMDA-NO-RyR pathway, 3) To test the hypothesis that the light/GLU-induced up-regulation of Per2 requires expression of Per in early night. This study will contribute to understanding the light signaling mechanisms in the context of the cellular organization of the SCN.

描述（由申请人提供）：视交叉上核（SCN） 下丘脑被认为是哺乳动物昼夜节律的主要计时器 节律，表现出神经元放电率模式近24小时的长度在 非周期性环境中的动物SCN的神经元节律可以是 相位延迟响应于在深夜给出的光脉冲， 与啮齿类动物活动节律中类似的相位延迟相关。尽管 作为生物钟的核心作用，SCN的新兴图片是一个 内部异质性。关于次区域如何对全球化作出贡献， 作为一个整体的SCN的功能。有趣的是，在仓鼠体内， 在SCN内对钙结合蛋白，钙结合蛋白-D28 k免疫反应 （CaBP），与节律产生相关，似乎特别 对光刺激有反应的。然而，大鼠缺乏这种独特的CaBP， 次区域。相反，类似区域可以是包含以下项的不同子区域： 钙视网膜蛋白（CN）免疫反应细胞。SCN保留其时钟属性 在体外，对神经化学物质的反应表现出类似的相位延迟， 光的信号，谷氨酸（GLU），在深夜。下游 通讯包括GLU与NMDA受体的结合，Ca 2+内流，一氧化氮 (NO)产生，并通过ryanodine受体（RyR）激活Ca 2+（I）。 光或葡萄糖刺激在深夜也上调两个时钟基因， Per 1和Per 2。这项提案将调查参与的信号通路， 光诱导的Per 1和Per 2在夜晚早期上调。具体目标 1）为了验证光诱导的Per 1和 Per 2定位于SCN的特定子区域，2）为了检验假设 GLU诱导的Per 1和Per 2在夜晚早期的上调信号 通过NMDA-NO-RyR途径，3）为了检验假设， 光/葡萄糖诱导的Per 2上调需要Per在细胞早期表达， 晚上本研究将有助于理解光信号 在SCN的蜂窝组织的上下文中的机制。