Cellular Organization of the Circadian Light Response

昼夜节律光反应的细胞组织

• 批准号: 6613710
• 负责人: Jennifer W Mitchell
• 金额: $ 4.42万
• 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/6613710
• 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(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，表现出近24小时长的神经元放电频率模式 处于非周期性环境中的动物。SCN的神经元节律可以是 相位延迟是对凌晨给出的光脉冲的响应，这 与啮齿动物活动节律中类似的阶段延迟相关。尽管 它作为生物钟的中心角色，正在浮现的SCN图像是 内部异质性。人们对次区域如何影响全球经济增长知之甚少。 SCN作为一个整体的功能。有趣的是，在仓鼠体内，细胞的一个子集 在钙结合蛋白Calbindin-D28k免疫反应阳性的SCN内 (CABP)，与节奏生成相关，似乎特别 对光刺激有反应的。然而，老鼠缺乏这种独特的CABP 次区域。相反，一个类似的区域可以是一个不同的分区域，包括 Calretinin(CN)免疫反应阳性细胞。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)，在清晨。下游 通讯包括GLU与NMDA受体的结合、钙离子内流、一氧化氮 (NO)通过兰尼定受体(RyR)产生和激活钙离子(I)。 早晚的光线或GLU刺激也会上调两个时钟基因， PER1和PER2。这项提案将研究涉及到的信号通路 光照诱导的PER1和PER2在夜间表达上调。具体目标 1)检验光诱导PER1和PER1上调的假说 PER2定位于SCN的特定亚区，2)检验假说 GLU诱导的PER1和PER2在夜间上调的信号 通过NMDA-NO-RyR途径，3)检验假设 光/GLU诱导的PER2上调需要早期PER的表达 晚上好。这项研究将有助于理解光信号 在SCN的细胞组织的背景下的机制。