Fractal Regulatory Function of the Circadian System

昼夜节律系统的分形调节功能

• 批准号: 8646975
• 负责人: Kun Hu
• 金额: $ 23.74万
• 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 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8646975
• 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费解的现象之一是在 生理系统的范围(即，波动的结构在不同的时间尺度上相似)，这 挑战维持生理恒定的传统动态论 大量研究证明了分形控制的重要性，并以简化的分形为例进行了说明 在衰老和病理条件下，心脏和活动的控制，最重要的是，通过 减少的分数维心脏控制对生存率降低的预测价值。尽管显然重要的是 分形现象，到目前为止，还没有在任何神经中建立起分形控制的潜在机制 或生理系统。PI最近的研究表明，昼夜节律系统关键地参与了 多时间尺度下运动活动的分形控制。该提案将正式评估生理上的 昼夜节律系统的分形调节功能的意义和神经生物学基础。这个 主要目标是确定昼夜节律系统传递信息的神经元节点和路径。 分形活动控制。在前两年的指导阶段，Pi和他的同事们已经完成了 分析揭示了中心昼夜节律系统的变化对分形活动控制( 最初提出的具体目标1)。新的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性活动控制减少。在接下来的三年 独立的研究阶段将允许PI实现主要研究目标，并帮助将PI建立为 该领域的独立研究人员。具体目标是：1)确定昼夜节律的影响 2)识别和验证活动控制中的神经元节点(S) 有助于控制分形活动的网络及其相互作用。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。更好地了解神经元电路 参与昼夜节律和活动调节应该为改善诊断和治疗提供有用的指导 与昼夜节律有关的睡眠和行为障碍的治疗。