Food Entrainable Circadianm Oscillator

描述（由申请人提供）：有限的食物供应时间窗口同步行为和生理昼夜节律的能力是有充分记录的。昼夜节律的这些变化被认为是由昼夜节律定时系统（CTS）中的食物可携带振荡器（FEO）提供的，该系统独立于光可携带起搏器——视交叉上核（SCN）。然而，FEO的（神经）解剖位点和分子机制仍未得到解决。Saper实验室最近的研究发现，下丘脑背内侧核（DMH）是食物携带的昼夜节律表达的关键结构，支持DMH可能具有FEO功能的概念。目前的建议旨在进一步表征：1)DMH产生昼夜节律的分子机制；2) DMH在协调外周组织振荡器限制摄食中的作用；3) DMH夹带的分子基础。通过了解DMH的分子基础以及DMH如何调节CTS功能，可以开发出治疗策略和诊断方法，以缓解基于CTS的昼夜节律、睡眠-觉醒以及可能的代谢紊乱。了解FEO-CTS相互关系的（神经）生物学可能对以下患者具有重要的临床应用价值：1)接受持续的肠外营养，而不是昼夜节律优化的肠外营养；2)安排食物和光线照射的时间，以尽量减少不同步，例如时差。通过了解FEO的神经解剖学和分子基础，以及FEO如何调节CTS功能，可以开发出治疗策略和诊断方法，以缓解基于FEO-CTS的昼夜节律、睡眠-觉醒以及可能的代谢紊乱。

DESCRIPTION (provided by applicant): The ability of restricted temporal windows of food availability to synchronize behavioral and physiological circadian rhythms to is well documented. These changes in circadian rhythms are thought to be sub served by a food-entrainable oscillator (FEO) in the circadian timing system (CTS) that is independent of the light entrainable pacemaker, the suprachiasmatic nucleus (SCN). The (neuro)anatomical locus and molecular mechanisms of the FEO have, however, remained unresolved. Recent work by the Saper laboratory has identified the dorsomedial hypothalamic nucleus (DMH) as a critical structure for the expression of food entrained circadian rhythms, supporting the concept that the DMH may function as a FEO. The present proposal is aimed at the further characterization of: 1) the molecular mechanism by which the DMH generates circadian rhythms; 2) the role of the DMH in coordinating peripheral tissue oscillators to restricted feeding; and 3) the molecular basis of DMH entrainment. By understanding the molecular-basis of the DMH and how the DMH modulates CTS function, therapeutic strategies and diagnostic approaches may be developed to alleviate circadian, sleep-wake and, possibly, metabolic disorders with a CTS basis. Understanding the (neuro)-biology of the FEO-CTS interrelationship may have significant clinical applications for 1) patients receiving continuous, as opposed to circadian optimized, parenteral nutrition; and 2) scheduling food- and light-exposure timing for minimizing desynchrony, e.g., jet-lag. By understanding the neuroanatomical and molecular basis of the FEO and how the FEO modulates CTS function, therapeutic strategies and diagnostic approaches may be developed to alleviate circadian, sleep-wake, and, likely, metabolic disorders with a FEO-CTS basis.