Revealing the Palatable Meal-Inducible Circadian Oscillator

昼夜节律是生物的基本内源性特性，可以在地球上大多数生物的行为和生理中观察到。这些日常节律是由一个自主的昼夜节律起搏器控制的。尽管昼夜节律产生的分子机制已经被深入研究，但越来越多的证据表明，存在一种新的昼夜节律起搏器，它可以在没有标准昼夜节律分子机制的情况下振荡。这些新奇的起搏器是通过奖赏系统的激活而显示出来的。利用最先进的昼夜节律行为记录设备和由首席研究员开发的实时昼夜节律基因报告，该项目揭示了美味膳食揭示的新型非规范昼夜节律起搏器的功能意义。该项目为各个学习阶段的个人提供了机会，从高中生到博士后学员，参与实验，促进对非规范昼夜节律起搏器的作用和功能的理解。这个项目的另一个目标是将科学知识传播给年轻一代的学习者。为此，首席研究员和学员参与外展计划，在达拉斯/沃斯堡地区代表性不足的初中和高中学生的课堂上分享他们的昼夜节律知识。哺乳动物昼夜节律系统是一个由振荡器组成的分层网络，以最佳方式协调行为和生理与日常环境循环。下丘脑的视交叉上核（SCN）处于这个层次的顶端，因为它与光-暗循环同步，这通常是主要的环境循环。首席研究员的实验室最近发现，定时获得美味的食物揭示了突变小鼠的内源性行为节律，其中所有典型的昼夜节律振荡器都在基因上被禁用。这种揭示的节律，即美味膳食诱导的昼夜节律振荡器（PICO），在美味膳食摄食计划终止后，在自由摄食下持续几个周期。在这个项目中，研究者使用分子工具集来检查和绘制多巴胺奖励输入途径的作用，这些途径可以唤起pico驱动的行为节奏。该项目还揭示了SCN和PICO如何协调外周组织中的昼夜节律振荡器，并优化调节生理事件以适应环境的日常周期。因此，该项目将改变目前对哺乳动物多振荡器昼夜节律网络的理解，这对生理和行为的时间调节至关重要，以最佳地适应环境的日常变化。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Circadian rhythms are fundamental endogenous properties of living organisms that can be observed in behavior and physiology in most living organisms on the earth. Those daily rhythms are governed by an autonomous circadian pacemaker. Although the molecular mechanism of the circadian rhythm generation has been studied in depth, accumulating evidence suggests the existence of novel circadian pacemakers that can oscillate without the canonical circadian molecular machinery. These novel pacemakers are revealed by the activation of a reward system. With state-of-the-art circadian behavior recording apparatus and real-time circadian gene-reporting developed by the principal investigator, this project uncovers the functional significance of the novel non-canonical circadian pacemaker revealed by palatable meals. This project provides opportunities to individuals at all stages of learning, from high school students to postdoctoral trainees, to participate in experiments that advance understanding of the role and function of the non-canonical circadian pacemaker. An additional goal of this project is to extend scientific knowledge to a young generation of learners. To this end, the principal investigator and trainees engage in outreach programs to share their knowledge of circadian rhythms in classrooms of underrepresented middle and high school students in the Dallas/Fort Worth area.The mammalian circadian system is a hierarchical network of oscillators optimally coordinating behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy because it synchronizes to the light-dark cycle, which is often the dominant environmental cycle. The laboratory of the principal investigator recently discovered that timed access to a palatable meal reveals an endogenous behavioral rhythm in mutant mice, of which all the canonical circadian oscillators were genetically disabled. This revealed rhythm, the palatable meal-inducible circadian oscillator (PICO), persists for several cycles under ad libitum feeding after termination of the palatable meal feeding schedule. In this project, the investigator uses molecular tool sets to examine the role of and map the dopamine reward input pathways that evoke the PICO-driven behavior rhythm. This project also uncovers how the SCN and PICO coordinate circadian oscillators in peripheral tissues and optimally tune physiological events to adapt to environmental daily cycles. The project thereby will transform current understanding of the multi-oscillator circadian network in mammals, which is critically involved in the temporal regulation of physiology and behavior to optimally adapt to daily changes in the environment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.