Finding time for dinner: neural and molecular mechanisms of food-entrainable circadian clocks

哺乳动物的行为和生理是由大脑和外周器官和组织中的内源性昼夜节律（24小时）时钟调节的。这些生物钟产生每天的睡眠-觉醒、食欲和体温的节律，并协调所有器官系统的功能与每天的明暗和用餐时间的周期。位于下丘脑的主生物钟对于使日常节律与明暗周期同步至关重要，但与进餐时间的同步是由一个或多个未知位置的其他生物钟介导的。我们的研究旨在了解食物调节日常节奏的大脑机制。最近的进展，在分子生物学的昼夜节律计时已经确定了一些基因，表现出昼夜节律的表达，并形成连锁反馈回路，产生自我维持，细胞自主节律。我们将使用免疫细胞化学和光度技术来测量生物钟基因，并确定与每天一到两次进餐时间同步振荡的大脑区域。我们将探讨的作用，特定的节奏大脑区域的控制进餐同步节奏，使用病变技术。我们将探索特定的时钟基因的作用，利用时钟基因突变小鼠的膳食同步的节奏。最后，我们将描述用餐时间和食物剥夺对行为和生理节律重新同步的速率的影响，以下相移的光暗周期，模拟东或西旅行或轮班工作轮换。这些研究的结果将阐明食物调节日常节律的神经和分子机制，并可能建议最大限度地减少旅行或轮班后昼夜节律中断的技术。

The behaviour and physiology of mammals is regulated by endogenous circadian (24 h) clocks in the brain and in peripheral organs and tissues. These clocks generate daily rhythms of sleep-wake, appetite and body temperature and coordinate the functions of all organ systems with daily cycles of light-dark and mealtimes. A master circadian clock located in the hypothalamus is critical for synchronizing daily rhythms to light-dark cycles, but synchrony to mealtimes is mediated by one or more other circadian clocks at an unknown location. Our research aims to understand the brain mechanisms by which food regulates daily rhythms. Recent advances in the molecular biology of circadian timekeeping have identified a number of genes that exhibit circadian rhythms of expression, and that form interlocking feedback loops that produce self-sustaining, cell autonomous rhythmicity. We will use immunocytochemical and photometric techniques to measure clock genes and identify brain regions that oscillate in synchrony with one or two daily mealtimes. We will explore the role of specific rhythmic brain regions in the control of meal synchronized rhythms, using lesion techniques. We will explore the role of specific clock genes for meal synchronized rhythms using clock gene mutant mice. Finally, we will characterize the effects of meal timing and food deprivation on the rate at which behavioural and physiological rhythms re-synchronize following phase shifts of the light-dark cycle, simulating east or west travel or shift work rotations. The results of these studies will clarify neural and molecular mechanisms by which food regulates daily rhythms and may suggest techniques for minimizing disruption of circadian rhythms following travel or shift rotation.