REGULATION OF THE MAMMALIAN CIRCADIAN SYSTEM

哺乳动物昼夜节律系统的调节

• 批准号: 6390675
• 负责人: CHRISTOPHER SCOTT COLWELL
• 金额: $ 15.96万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390675
• 关键词: Mammalia; NMDA receptors; bicuculline; calcium flux; calcium indicator; circadian rhythms; electrophysiology; evoked potentials; glutamates; hypothalamus; immunocytochemistry; membrane potentials; neuroregulation; photobiology; retina; suprachiasmatic nucleus; tissue /cell preparation; video microscopy; voltage /patch clamp

DESCRIPTION (applicant's abstract): Most organisms, including humans, exhibit daily rhythms in their behavior and physiology. In most cases, these rhythms are generated by endogenous processes referred to as circadian oscillators. These oscillators provide temporal structure to an organism's physiological processes. Nearly all functions of the body show significant daily variations including arousal, cognition, learning, memory, motor performance and perception. This temporal variation obviously plays an important role in the body's homeostatic mechanisms and has a major impact on the function of the nervous system. In order to function adaptively, circadian oscillators must be synchronized to the environment and the daily cycle of light and dark is the dominant cue used by organisms, including humans, to synchronize their biological clocks to the environment. In humans, desynchronization results in symptoms of fatigue, gastrointestinal distress, and poor cognitive performance. Thus, a major goal of this research area, and the focus of this grant proposal, is to understand the mechanisms by which light acts to synchronize the circadian oscillator located in the suprachiasmatic nucleus (SCN). Previous work has shown that glutamate is a transmitter that conveys photic information to the SCN and the glutamate receptors play a critical role in mediating the response of the circadian system to photic stimulation. One of the primary goals of this proposal is to explore the possibility that glutamatergic retinal input to the SCN is rhythmic on a circadian time scale and to define the mechanisms underlying this daily regulation. Certainly understanding the mechanisms that mediate the long-term modulation of glutamatergic synaptic transmission are of general interest and importance in neuroscience research. In addition, a number of other related questions will be addressed. Is this rhythm restricted to cells in specific regions of the SCN or a general feature of synaptic communication in the SCN? Do anatomically defined cell populations within the SCN differ in their membrane properties and response to glutamatergic stimulation? Is there a daily rhythm in basal and glutamatergic-stimulated calcium levels in SCN cells? The presence of such rhythms would have important implications for information processing within the SCN but also for the cell biology of SCN neurons. Finally, the proposed work will determine whether a model developed to explain synchronization of molluscan circadian oscillators can be applied to the mammalian SCN.

描述（申请人的摘要）：包括人类在内的大多数生物展览 每日的行为和生理节奏。在大多数情况下，这些节奏 由称为昼夜节律振荡器的内生过程产生。 这些振荡器为生物的生理提供时间结构 过程。身体几乎所有功能都显示出明显的每日变化 包括唤醒，认知，学习，记忆，运动表现和 洞察力。这种时间变化显然在 身体的稳态机制，对 神经系统。为了适应功能，昼夜振荡器必须是 与环境同步，光与黑暗的每日周期是 包括人类在内的有机体使用的主导提示使他们的同步 生物钟到环境。在人类中，不同步导致 疲劳症状，胃肠道困扰和认知表现不佳。 因此，该研究领域的主要目标以及该赠款提案的重点， 是要了解光的机制来同步 昼夜节律振荡器位于上核（SCN）中。以前的 工作表明谷氨酸是传达光学信息的发射器 到SCN和谷氨酸受体在介导 昼夜节律对光刺激的反应。主要之一 该建议的目标是探索谷氨酸视网膜的可能性 SCN的输入是有节奏的，在昼夜节律的时间范围内 该日常调节的基础机制。当然了解 介导谷氨酸能突触的长期调节的机制 传播在神经科学研究中具有普遍关注和重要性。 此外，还将解决许多其他相关问题。是这个 节奏仅限于SCN或一般特征的特定区域的细胞 SCN中的突触通信？进行解剖学定义的细胞群体 在SCN内的膜特性不同，对 谷氨酸能刺激？是否有每天的基础节奏和 SCN细胞中谷氨酸能刺激的钙水平？存在这样的存在 节奏将对信息处理中的信息处理具有重要意义 SCN也适用于SCN神经元的细胞生物学。最后，拟议的工作 将确定是否开发了用于解释同步的模型 软体动物昼夜节律振荡器可以应用于哺乳动物SCN。