Communication in the Mammalian Circadian Clock: The Role of Nitric Oxide

哺乳动物昼夜节律钟中的通讯：一氧化氮的作用

基本信息

批准号：
8011525
负责人：
Horacio O De La Iglesia
金额：
$ 3.16万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8011525
关键词：
Accounting Address Affect American Animals Area Argentina Authorship Behavior Behavioral Biochemistry Biological Assay Biological Clocks Biological Rhythm Body Temperature Books Brain Budgets Cell Nucleus Cells Chemicals Chronobiology Circadian Rhythms Collaborations Communication Communities Complement Country Coupled Coupling Darkness Data Development Disease Dissociation Endocrine Equipment Fluorescent in Situ Hybridization Funding Future Gene Expression Generations Genes Goals Hamsters Health Histocytochemistry Hormones Hour Housing Human Human Resources Hypothalamic structure In Vitro Injection of therapeutic agent Intention Knowledge Laboratories Learning Left Light Luciferases Mammals Mediating Modeling Molecular Biology Monitor Motor Activity Neurobiology Neurons Nitric Oxide Nitric Oxide Donors Operative Surgical Procedures Output Pacemakers Pathology Pathway interactions Phase Physiologic pulse Physiological Physiology Postdoctoral Fellow Procedures Process Publications Radioactive Rattus Reading Regulation Reporting Research Research Personnel Role Running Schedule Screening procedure Signal Transduction Signal Transduction Pathway Signaling Molecule Sleep Stages Sleep Wake Cycle Slice Societies Stimulus Students System Techniques Testing Time Tissues Touch sensation Training Travel Universities Visit Work base career circadian behavioral rhythms circadian pacemaker college experience extracellular graduate student in vivo insight intercellular communication light effects parent grant relating to nervous system research study shift work success suprachiasmatic nucleus symposium tool transmission process

项目摘要

DESCRIPTION (provided by applicant): The mammalian hypothalamic suprachiasmatic nucleus (SCN) contains a master circadian clock that governs physiological and behavioral rhythms. The SCN is constituted of single-cell neuronal oscillators that are coupled and generate a coherent circadian output. The mechanisms and transmitters that are responsible for interneuronal coupling within the SCN have not been completely elucidated. The overall goal of this proposal is to study the role of nitric oxide (NO), a gaseous transmitter present in SCN cells, on SCN intercellular communication. Specific Aim C.1 seeks to establish the role of NO-mediated coupling on the determination of the free-running period of the pacemaker within the SCN. Specific Aim C.2 will assess the role of NO intercellular signaling within the SCN in light-induced phase resetting of circadian rhythms. Finally, Specific Aim C.3 will evaluate -both in vitro and in vivo - the role of NO signaling in the resynchronization between the ventrolateral and dorsomedial SCN after they have been desynchronized by exposing animals to an abrupt phase advance of the light-dark cycle. The proposed experiments will provide insights into the mechanisms and signals responsible for synchronization between SCN cells. Furthering our knowledge of how SCN cells work together to constitute a master clock is key to understand and treat circadian pathologies. PUBLIC HEALTH RELEVANCE: The physiology and behavior of mammals, including humans, show robust 24-hour oscillations that are generated and coordinated by an area within the brain's hypothalamus called the suprachiasmatic nucleus. This nucleus contains a biological clock that is made up by several thousand neurons that are themselves clock neurons capable of oscillating independently. Thus, the synchronization between neurons within the suprachiasmatic nucleus is essential for the normal timing of physiological and behavioral rhythms such as the release of hormones and the sleep-wake cycle. Revealing how these neurons communicate with each other is critical to understand the neural bases of some disorders causing abnormal timing of these functions as well as to treat pathologies that result from challenges associated with our modern around-the- clock society, such as traveling across time zones or nocturnal shift work schedules.

描述（由申请人提供）：哺乳动物下丘脑上张核（SCN）包含一个控制生理和行为节律的昼夜节律。 SCN由单细胞神经元振荡器组成，这些振荡器耦合并产生连贯的昼夜节目。尚未完全阐明负责SCN内核元偶联的机理和发射器。该提案的总体目标是研究SCN细胞中存在的气态发射器一氧化氮（NO）在SCN细胞间通信中的作用。具体目的C.1试图确定无介导的耦合在确定SCN中起搏器自由运行时期的作用。具体目标C.2将评估SCN内无细胞间信号传导在光诱导的昼夜节律复位中的作用。最后，特定的目标c.3将在体外和体内评估 - 无信号传导在腹外侧和背侧SCN之间的重新同步后，通过将动物暴露于灯光循环的突然阶段，使它们在腹外侧和背侧SCN之间进行重新同步。提出的实验将提供有关负责SCN细胞之间同步的机制和信号的见解。进一步发展我们对SCN细胞如何共同工作以构成主时钟的知识是理解和治疗昼夜节律病理的关键。公共卫生相关性：包括人类在内的哺乳动物的生理和行为，表现出强大的24小时振荡，这些振荡是由大脑下丘脑中的一个称为suparachiasmmasmatic核产生和协调的。该核包含一个生物钟，由数千个神经元组成，它们本身就是能够独立振荡的时钟神经元。因此，界核内神经元之间的同步对于生理和行为节奏的正常时机（例如激素的释放和睡眠觉醒循环）至关重要。揭示这些神经元如何互相交流对于了解某些疾病的神经碱基至关重要，从而导致这些功能异常的时间以及治疗与现代围环社会相关的挑战所带来的病理学，例如跨时区旅行或差不多转移工作时间表。