REGULATION OF THE MAMMALIAN CIRCADIAN SYSTEM

描述(申请人摘要)：大多数生物，包括人类，展示 它们的行为和生理的日常节律。在大多数情况下，这些节奏 是由称为昼夜节律振荡器的内生过程产生的。 这些振荡器为生物体的生理活动提供了时间结构 流程。身体的几乎所有功能每天都有显著的变化。 包括唤醒、认知、学习、记忆、运动表现和 感知力。这种时间变化显然在 体内的动态平衡机制，并对人体的功能有重大影响 神经系统。为了自适应地发挥作用，昼夜节律振荡器必须 与环境和每日的明暗周期同步的是 包括人类在内的有机体用来同步他们的 生物钟对环境的影响。在人类中，去同步化导致 疲劳、胃肠道不适和认知能力差的症状。 因此，这一研究领域的一个主要目标，也是这项拨款提案的重点， 就是了解光的作用机制，以使 昼夜节律振荡器位于视交叉上核。上一首 研究表明，谷氨酸是一种传递光信息的发射器 对SCN和谷氨酸受体起着关键作用。 昼夜节律系统对光刺激的反应。其中一个主要的 这项提议的目标是探索谷氨酸能视网膜 SCN的输入在昼夜时标上是有节奏的，并定义 这一日常调控背后的机制。当然，要理解 谷氨酸能突触的长时程调节机制 传递在神经科学研究中具有普遍的兴趣和重要性。 此外，还将讨论一些其他相关问题。是这个吗 节律局限于SCN的特定区域的细胞或一般特征 在SCN中的突触通讯吗？做解剖定义的细胞群体 在SCN内，它们的膜性质和对 谷氨酸能刺激？是否有一个每日节律的基础和 谷氨酸能刺激SCN细胞的钙水平？这些人的存在 节奏将对信息处理具有重要的意义 SCN还用于SCN神经元的细胞生物学研究。最后，提出了本文的工作建议 将决定是否开发一个模型来解释 软体动物昼夜节律振荡器可以应用于哺乳动物的SCN。

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.