REGULATION OF THE MAMMALIAN CIRCADIAN SYSTEM

描述（申请人摘要）：大多数生物体，包括人类， 他们的行为和生理的日常节奏。在大多数情况下，这些节奏 是由称为昼夜节律振荡器的内源性过程产生的。 这些振荡器为生物体的生理活动提供了时间结构。 流程.几乎身体的所有功能都表现出明显的每日变化 包括唤醒、认知、学习、记忆、运动表现和 perception.这种时间上的变化显然在 身体的自我平衡机制，并有一个主要影响的功能， 神经系统为了适应性地发挥作用，昼夜节律振荡器必须 与环境同步的光和暗的日常周期是 包括人类在内的生物体用来同步它们的 生物钟对环境的影响在人类中，去铁化导致 疲劳、胃肠道不适和认知能力差的症状。 因此，这个研究领域的一个主要目标，也是这个拨款申请的重点， 是了解光的作用机制， 位于视交叉上核（SCN）的昼夜节律振荡器。先前 研究表明，谷氨酸是一种传递光信息的递质， 与SCN和谷氨酸受体在介导 昼夜节律系统对光刺激的反应。的一个主要 本研究的目的是探讨视网膜神经元神经元 SCN的输入在昼夜节律时间尺度上是有节奏的，并且为了定义 这种日常管理的基础。当然， 介导突触长时程调节的机制 传递是神经科学研究中的普遍兴趣和重要性。 此外，还将讨论其他一些相关问题。这是 节律仅限于SCN特定区域的细胞或一般特征 突触通讯的关键吗解剖学上定义的细胞群 在SCN内，它们的膜特性和对 神经刺激？基础胰岛素是否有每日节律， SCN细胞中的钙离子水平？出现该等 节奏将有重要的影响，信息处理内 SCN的细胞生物学，但也SCN神经元的细胞生物学。最后，建议的工作 将决定是否开发一个模型来解释同步的 软体动物的昼夜节律振荡器可应用于哺乳动物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.