Revealing the Palatable Meal-Inducible Circadian Oscillator

揭示可口的膳食诱导的昼夜节律振荡器

• 批准号: 1931115
• 负责人: Shin Yamazaki
• 金额: $ 70万
• 依托单位: University of Texas Southwestern Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1931115&HistoricalAwards=false
• 关键词: Revealing; Palatable; Meal; Inducible; Circadian

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.

昼夜节律是生物体的基本内源性特性，可以在地球上大多数生物体的行为和生理中观察到。这些日常节奏是由自主的昼夜节律起搏器控制的。虽然昼夜节律产生的分子机制已被深入研究，越来越多的证据表明，存在新的昼夜节律起搏器，可以振荡没有典型的昼夜节律分子机制。 这些新的起搏器是通过激活奖励系统来揭示的。通过主要研究者开发的最先进的昼夜节律行为记录设备和实时昼夜节律基因报告，该项目揭示了可口的膳食揭示的新型非规范昼夜节律起搏器的功能意义。该项目为处于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，以促进对非规范昼夜节律起搏器的作用和功能的理解。该项目的另一个目标是向年轻一代学习者传授科学知识。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对昼夜节律的知识。哺乳动物昼夜节律系统是一个分层的振荡器网络，最佳地协调行为和生理与日常环境周期。下丘脑的视交叉上核（SCN）位于这一层次的顶端，因为它服从于明暗周期，而明暗周期通常是占主导地位的环境周期。首席研究员的实验室最近发现，定时获得可口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是遗传性残疾。这种揭示的节律，可口的膳食诱导的昼夜节律振荡器（皮科），持续几个周期下随意喂养可口的膳食喂养时间表终止后。在这个项目中，研究人员使用分子工具集来检查引起PICO驱动的行为节律的多巴胺奖励输入途径的作用并绘制它们。该项目还揭示了SCN和皮科如何协调外周组织中的昼夜节律振荡器，并优化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，该网络关键涉及生理和行为的时间调节，以最佳地适应环境的日常变化。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

A time memory engram embedded in a light-entrainable circadian clock

嵌入光诱导生物钟的时间记忆印迹

• DOI: 10.1016/j.cub.2023.10.027
• 发表时间: 2023
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Ehichioya, David E.;Taufique, S.K. Tahajjul;Farah, Sofia;Yamazaki, Shin
• 通讯作者: Yamazaki, Shin

Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation

• DOI: 10.1073/pnas.2318274120
• 发表时间: 2023-12-26
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Xie，Pancheng;Xie，Xiaowen;Liu，Yi
• 通讯作者: Liu，Yi