NEURAL CONTROL OF SUPRACHIASMATIC FUNCTION

使用器官培养方法，拟议的研究旨在 系统地评估假定的发射机的影响， 以及它们的药理学类似物和拮抗剂， 由生物钟表达的加压素释放节律 位于视交叉上的外植体中。 两个系列的实验 提出了神经化学物质的不同方面， 视交叉上核（SCN）的组织， 功能视角。 在第一个项目中，实验将 检查传入递质系统的功能作用， SCN的中央控制及其昼夜输出。 重点 在这些实验中， 被认为与主要神经输入有关的递质， SCN，即乙酰胆碱、神经肽Y和血清素。 在 相反，第二个项目将接近功能 核内神经递质系统的组织 SCN中的通信。 虽然固有的细胞 SCN的神经化学本质上是异质的，这一系列 的实验将专门集中在潜在的作用， GABA作为一种内在的计时成分， 调节昼夜节律的产生和表达 的SCN。 在这两个项目中使用的第一种方法需要 检查发射器和/或其 相关的类似物和拮抗剂， 起搏器特性，加压素节律的相位。 这 方法将在后续研究中扩展到：1）检查 剂量与移相作用之间的关系 （2）确定其特异性拮抗剂是否 药理学作用可以阻断由这种药物引起的相移。 3）系统地检查相移响应 急性药物给药在不同的时间在整个 整个生理周期 因为显性节奏的相位是 被认为直接反映了生物钟的状态， 观察到急性药物给药诱导 加压素节律会暗示相关的递质 SCN的细胞成分的调节涉及 产生昼夜节律。 此外，研究发现， 药剂的相移作用取决于 给药将表明该发射器在以下方面发挥作用： 介导SCN的夹带及其昼夜输出。 鉴于许多生理系统受到 通过昼夜神经信号，拟议的研究，这提供了一个 有机会确定特定药物是否可以直接改变 生物钟，可以提供在治疗中是有用的， 诊断和理解身体和精神疾病， 与生物钟的紊乱有关。

Using organ culture methods, the proposed studies are designed to systematically evaluate the effects of putative transmitters as well as their pharmacological analogues and antagonists on the rhythm of vasopressin release expressed by the circadian clock located in suprachiasmatic explants. Two series of experiments are proposed in which different aspects of the neurochemical organization of the suprachiasmatic nucleus (SCN) from a functional perspective. In the first project, experiments will examine the functional roles of afferent transmitter systems in the central control of the SCN and its circadian output. Emphasis in these experiments has been placed on those putative transmitters thought to be associated with major neural inputs to the SCN, namely acetylcholine, neuropeptide Y and serotonin. In contrast, a second project will approach the functional organization of transmitters systems underlying intranuclear communication in the SCN. Although the inherent cellular neurochemistry of the SCN is heterogeneous in nature, this series of experiments will focus exclusively on the potential role of GABA as an intrinsic timekeeping component involved in mediating the generation and expression of the circadian rhythms by the SCN. The first approach utilized in both of these projects entails an examination of the effects of the transmitters and/or their related analogues and antagonists on an easily measured pacemaker property, the phase of the vasopressin rhythm. This approach will be extended in subsequent studies to: 1) examine the relationship between dose and the phase-shifting action of the agent; 2) determine whether specific antagonists of its pharmacological action can block phase shifts induced by this agent; and 3) systematically examine the phase-shifting responses to acute drug administration at various times throughout the entire circadian cycle. Since the phase of an overt rhythm is thought to directly reflect the state of the circadian clock, the observation that acute drug administration induces phase shifts in the vasopressin rhythm would implicate the related transmitter in the regulation of cellular components of the SCN involved in generating circadian rhythms. Furthermore, the finding that the phase-shifting action of an agent is dependent on the time of administration would indicate that the transmitter plays a role in mediating the entrainment of the SCN and its circadian output. In view of the fact that many physiological systems are influenced by circadian neural signals, the proposed studies, which provide an opportunity to determine whether specific drugs can directly alter a circadian clock, may provide to be useful in the treatment, diagnosis and understanding of physical and metal illnesses that have been associated with a disorder in circadian timekeeping.