Fractal Regulatory Function of the Circadian System

昼夜节律系统的分形调节功能

• 批准号: 8529598
• 负责人: Kun Hu
• 金额: $ 23.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529598
• 关键词: AD 20; Aftercare; Aging; Alzheimer' s Disease; Anatomy; Behavior; Behavioral; Biological Markers; Biology; Cardiac; Cessation of life; Circadian Rhythms; Databases; Diagnosis; Double-Blind Method; Elderly; Experimental Animal Model; Fractals; Functional disorder; Genetic; Goals; Homeostasis; Hour; Human; Hypothalamic structure; Knock-out; Lead; Lesion; Light; Melatonin; Mentors; Modeling; Motor Activity; Neurobiology; Neurons; Pathology; Pathway interactions; Patients; Pattern; Phase; Physiological; Physiology; Placebo Control; Predictive Value; Rattus; Regulation; Research; Research Personnel; Sleep; Structure; Supervision; System; Systems Biology; Testing; Time; Tissue Sample; Training; Work; base; circadian pacemaker; improved; neuronal circuitry; neuropathology; randomized trial; relating to nervous system; restoration; suprachiasmatic nucleus; theories

One ofthe most puzzling phenomena in modern physiology is the existence of fractal patterns in a wide range of physiological systems (i.e., the structure of fluctuations are similar at different time scales), which challenges the traditional theory of homeostasis of maintaining physiologic constancy The physiological importance of fractal control is demonstrated In numerous studies and exemplified by reduced fractal cardiac and activity controls with aging and under pathological conditions, and most importantly, by the predictive value of reduced fractal cardiac control for decreased survival.. Despite the clear importance of fractal phenomena, to date, no underlying mechanism has been established for fractal control in any neural or physiological system. The Pi's recent studies indicate that the circadian system is critically involved in the fractal control of motor activity at multiple time scales. The proposal will formally assess the physiological significance and the neurobiological basis ofthe fractal regulatory function ofthe circadian system. The primary goal is to identify the neuronal nodes and pathways through which the circadian system imparts fractal activity control. During the previous 2-year mentored phase, PI and his colleagues have completed the analyses to reveal the effects of changes in the central circadian system on fractal activity control (the originally proposed Specific Aim 1). New results provided first direct evidence that dysfunction ofthe central circadian pacemaker leads to reduced fractal activity control in humans. The subsequent three years of the independent research phase will allow the PI to achieve the main research goal and help establish the PI as an independent researcher in the field. The specific aims are 1) to determine the effects of circadian misalignment on fractal activity control; and 2) to identify and validate neuronal node(s) in the activity control network and their interactions that contribute to fractal activity control. Achieving these aims will provide the neurophysiologic basis forthe first model of fractal control. Better understanding ofthe neuronal circuitry involving in circadian and activity regulation ought to provide useful guidance for improved diagnosis and treatment of circadian-related sleep and behavioral disturbances.

现代生理学中最令人困惑的现象之一是在一个广泛的 生理系统的范围（即，波动结构在不同时间尺度上是相似的）， 挑战了维持生理恒定性的内稳态的传统理论。 分形控制的重要性在许多研究中得到了证明，并通过减少分形 随着年龄的增长和病理条件下的心脏和活动控制，最重要的是， 降低分形心脏控制对降低生存率的预测价值。尽管很明显， 分形现象，迄今为止，还没有建立任何神经系统中分形控制的基本机制， 或生理系统。Pi最近的研究表明，昼夜节律系统与人类的生活方式密切相关。 运动活动在多个时间尺度上的分形控制。该提案将正式评估生理 意义和昼夜节律系统分形调节功能的神经生物学基础。的 主要目标是识别昼夜节律系统传递的神经元节点和通路 分形活性控制在过去的2年辅导阶段，PI和他的同事已经完成了 分析揭示了中央昼夜节律系统的变化对分形活动控制的影响（ 第一个具体目标（1）。新的研究结果提供了第一个直接证据，表明中枢神经系统功能障碍 昼夜节律起搏器导致人类分形活动控制减少。随后的三年， 独立研究阶段将允许PI实现主要研究目标，并帮助建立PI， 这一领域的独立研究者。具体目标是：1）确定昼夜节律的影响 分形活动控制上的不对准;以及2）识别和验证活动控制中的神经元节点 网络及其相互作用，有助于分形活动控制。实现这些目标将提供 第一个分形控制模型的神经生理学基础。更好地理解神经元回路 参与昼夜节律和活动调节应该为改善诊断提供有用的指导， 治疗昼夜节律相关的睡眠和行为障碍。