CRCNS: The balance between robustness and sensitivity in circadian synchrony
CRCNS:昼夜同步的鲁棒性和敏感性之间的平衡
基本信息
- 批准号:9098858
- 负责人:
- 金额:$ 18.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdvocacyAreaBeesBehaviorBiological ModelsBiological RhythmBiologyBrainCellsChemistryChronobiologyCircadian RhythmsCollaborationsComputer SimulationComputer softwareCoupledCouplingDataDevelopmentDoseEducationEducational process of instructingEnvironmentEquilibriumGeneral PopulationGenerationsGeneticHigh School FacultyHormonesIndividualInternationalJapanLearning ModuleLightMaintenanceMathematicsMeasuresMetabolismModelingMusNeurosciencesNeurotransmittersParticipantPeriodicityPhasePhysicsPhysiologyResearchRoleRunningSchoolsScientistSignal TransductionSleepSliceSocietiesStimulusStudentsSystemTestingTimeTrainingTravelVasoactive Intestinal Peptidecircadian pacemakerday lengtheducation researchflexibilitygamma-Aminobutyric Acidin vitro Modelin vivonoveloutreachprogramsreceptorresearch studyshift worksuprachiasmatic nucleustool
项目摘要
DESCRIPTION (provided by applicant):
Overview
The suprachiasmatic nucleus (SCN) serves as a circadian pacemaker that drives daily rhythms in vertebrate behavior and physiology. It generates robust, self-sustained oscillations that entrain to the local day-night cycle including hormone secretion, metabolism and sleep-wake. In addition, the SCN must adapt to slow seasonal changes in day length and, with travel across time zones, rapid shifts in the 24-h environment. It is an important and fundamental question how the oscillatory systems balance robust rhythmicity with flexible synchronization.
Intellectual Merit:
We hypothesize that opposing actions of two coupling agents contribute to the robust, yet sensitive, cycling of the network of SCN cells. Vasoactive intestinal peptide (VIP) and γ-aminobutyric acid (GABA) are key neurotransmitters involved in the generation and maintenance of SCN rhythms. Genetic and pharmacological experiments revealed central roles for VIP and its canonical receptor (VPAC2R) and GABA and GABAA receptors in synchronization among circadian cells. We will test the hypothesis that GABA signaling makes SCN timekeeping less precise but more amenable to phase shifting by external stimuli, such as light.
We will combine theoretical and experimental tools to study the synergistic actions of VIP and GABA for synchronization among cells and entrainment to the environment. The SCN provides an outstanding model system of coupled oscillators that can be studied in vivo, reduced and simplified to a slice or individual cells in vitro, and modeled in silico. Although it is comprisedof thousands of heterogeneous cells, the SCN offers a unique opportunity to understand the balance between reliable rhythmicity and adaptable synchrony. We have three specific research aims:
1. Data-driven modeling of two competing coupling mechanisms.
2. Experimental studies of GABA blockade and enhancement in wild-type and VIP-deficient mice.
3. Theoretical and experimental optimization of adjustment to shift work via dosing strategies of benzodiazopines.
Broader impacts
The proposed research includes the development of novel software (the "Entrainometer") for analysis of rhythm synchronization to a periodic input. This software will be freely available and
useful to a wide range of scientists wanting to reliably measure features of entrainment. The proposal also includes significant outreach, education, and research opportunities. Both Drs. Herzog and Herzel are deeply committed to training young scientists. Dr. Herzog founded the St. Louis Chapter of the Society for Neuroscience through which he runs major outreach activities including NeuroDay (1500 visitors), HealthFest (1500 visitors) and the St. Louis Area Brain Bee (40 competitors, 200 participants). He also runs a 1-week summer course for high school teachers that includes material on circadian rhythms. Both Drs. Herzog and Herzel have taught in and directed the International Chronobiology Summer School for many years (including 2014 in Sapporo, Japan). As the 2014 Program Chair for the Society for Research on Biological Rhythms, Dr. Herzog promoted advocacy to the general public (e.g., a discussion of school start times) and chronobiology education (e.g. how to use chronobiology to excite students about physics, chemistry, math and biology). He continues to share his enthusiasm for rhythms research as the 2014-1016 Chair of Fundraising for SRBR. As part of this collaboration, the PIs will develop "Modeling Circadian Clocks," a teaching module, for use by undergraduate and graduate educators around the world.
描述(由申请人提供):
概述
视交叉上核(SCN)作为一个昼夜节律的起搏器,驱动脊椎动物的行为和生理的日常节奏。它产生强大的,自我维持的振荡,夹带到当地的昼夜周期,包括激素分泌,代谢和睡眠-觉醒。此外,SCN必须适应白天长度的缓慢季节性变化,以及跨时区旅行,24小时环境的快速变化。振动系统如何平衡鲁棒节律性和柔性同步是一个重要而基本的问题。
智力优势:
我们假设两种偶联剂的相反作用有助于SCN细胞网络的稳健但敏感的循环。血管活性肠肽(VIP)和γ-氨基丁酸(GABA)是参与SCN节律产生和维持的关键神经递质。遗传和药理学实验揭示了VIP及其经典受体(VPAC 2 R)和GABA和GABAA受体在昼夜节律细胞之间的同步中的核心作用。我们将测试的假设,GABA信号使SCN计时不太精确,但更容易受到外部刺激,如光的相移。
我们将结合联合收割机的理论和实验工具,研究VIP和GABA的协同作用,同步细胞和夹带到环境中。SCN提供了一个出色的耦合振荡器模型系统,可以在体内研究,减少和简化为一个切片或单个细胞在体外,并在硅片建模。尽管SCN由成千上万的异质细胞组成,但它提供了一个独特的机会来了解可靠的节律性和适应性同步之间的平衡。我们有三个具体的研究目标:
1.两种竞争耦合机制的数据驱动建模。
2.在野生型和VIP缺陷小鼠中GABA阻断和增强的实验研究。
3.通过苯二氮卓类药物给药策略调整轮班工作的理论和实验优化。
更广泛的影响
拟议的研究包括开发新的软件(“Entrainometer”),用于分析节律同步到周期性输入。 该软件将免费提供,
对希望可靠地测量夹带特征的广泛科学家有用。该提案还包括重要的外联、教育和研究机会。赫尔佐格博士和赫泽尔博士都致力于培养年轻科学家。赫尔佐格博士创立了神经科学学会圣路易斯分会,通过该分会,他开展了主要的外展活动,包括NeuroDay(1500名游客),HealthFest(1500名游客)和圣路易斯地区脑蜜蜂(40名竞争对手,200名参与者)。他还为高中教师开设了一个为期一周的暑期课程,其中包括关于昼夜节律的材料。Herzog和Herzel博士多年来一直在国际时间生物学暑期学校任教并指导该学校(包括2014年在日本札幌举办的暑期学校)。作为生物节律研究学会2014年项目主席,Herzog博士促进了对公众的宣传(例如,讨论学校的开学时间)和时间生物学教育(例如如何使用时间生物学来激发学生对物理、化学、数学和生物的兴趣)。他继续分享他对节奏研究的热情,作为SRBR筹款的2014-1016主席。作为这项合作的一部分,PI将开发“建模昼夜节律时钟”,这是一个教学模块,供世界各地的本科生和研究生教育工作者使用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Erik Herzog其他文献
Erik Herzog的其他文献
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{{ truncateString('Erik Herzog', 18)}}的其他基金
BP-ENDURE St. Louis: A Neuroscience Pipeline
BP-ENDURE 圣路易斯:神经科学管道
- 批准号:
9429006 - 财政年份:2016
- 资助金额:
$ 18.9万 - 项目类别:
BP-ENDURE St. Louis: A Neuroscience Pipeline
BP-ENDURE 圣路易斯:神经科学管道
- 批准号:
9212974 - 财政年份:2015
- 资助金额:
$ 18.9万 - 项目类别:
CRCNS: The balance between robustness and sensitivity in circadian synchrony
CRCNS:昼夜同步的鲁棒性和敏感性之间的平衡
- 批准号:
9288233 - 财政年份:2015
- 资助金额:
$ 18.9万 - 项目类别:
CRCNS: The balance between robustness and sensitivity in circadian synchrony
CRCNS:昼夜同步的鲁棒性和敏感性之间的平衡
- 批准号:
9047972 - 财政年份:2015
- 资助金额:
$ 18.9万 - 项目类别:
BP-ENDURE: The St. Louis Neuroscience Pipeline
BP-ENDURE:圣路易斯神经科学管道
- 批准号:
10373954 - 财政年份:2015
- 资助金额:
$ 18.9万 - 项目类别:
BP-ENDURE St. Louis: A Neuroscience Pipeline
BP-ENDURE 圣路易斯:神经科学管道
- 批准号:
9023602 - 财政年份:2015
- 资助金额:
$ 18.9万 - 项目类别:
NEURONAL EXCITABILITY IN THE REGULATION OF CIRCADIAN RHYTHMS
昼夜节律调节中的神经元兴奋性
- 批准号:
8601192 - 财政年份:2013
- 资助金额:
$ 18.9万 - 项目类别:
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