Sympathetic Neural Recruitment, Modulation, and Vascular Coupling in Humans

研究计划目的：了解交感神经系统(SNS)在面对生理应激时控制血压和调节血流分布所使用的神经通讯策略。我们正在测试工作假说，即SNS表达一种复杂但确定性的语言，表现在它招募各种神经元家族以及修改神经元放电模式的时间。背景：生存依赖于外部和内部应激源快速和准确地传递到重要的内脏器官，导致处理压力的功能改变。例如，当你站起来时，为了防止血压下降而采取的矫正措施需要你体内的神经传感器之间的复杂联系，这些传感器向大脑通知问题，然后改变交感神经活动(SNA)的流出，以调整心脏和血管的功能，以保护血压。一般来说，神经系统依靠神经放电模式来准确地传达刺激的细节。然而，我们对社交网络系统用来交流和纠正应激诱导的生理障碍的神经语言的理解仍然非常肤浅。使用人类的直接神经记录，我们描述了复杂的SNS招募策略，包括：i)在基线时已经招募的轴突的放电频率的改变，ii)在应激期间招募更多的神经群体，以及iii)这些轴突放电模式的时间变化。我们现在的目标是提高我们对这些神经招募模式的控制机制以及根据血管收缩模式测量的血管对它们的解释的理解。*研究目标：1)确定与特定SNA模式相关的大脑区域和可能的神经控制机制，2)开发以滴定方式操纵这些通信模式的方法，以进一步研究感觉和交感神经系统之间的相互作用，以及3)根据血管收缩的程度量化SNA信号是如何被血管解释的。使用各种生理应激源，我们将评估SNA动作电位招募(显微神经学)、脑功能激活(神经成像)和肌肉血流量(超声和弥散相关光谱)之间的关系。这些研究具有很高的新颖性，解决了一个基本的动态平衡原理，即通过对压力的急性和慢性适应来提高动物的存活率。

Research Program Objective: Understand the neurological communication strategies used by the sympathetic nervous system (SNS) to control blood pressure and regulate the distribution of blood flow in the face of physiological stress. We are testing the working hypothesis that the SNS expresses a complex but deterministic language expressed in its recruitment of various families of neurons as well as modifications of the timing of the neuronal firing patterns. ******Background: Survival depends upon rapid and accurate communication of external and internal stressors to vital internal organs, leading to functional changes to deal with the stress. For example, corrective action taken to keep blood pressure from falling when you stand up requires an intricate linkage between neural sensors in your body that inform the brain about the problem which then modifies the outflow of sympathetic nerve activity (SNA) to adjust the function of heart and blood vessels to protect blood pressure. In general, neural systems rely on patterns of neural firing to communicate precisely the details of the stimulus. However, our understanding of the neural “language” used by the SNS to communicate and correct stress-induced physiological disturbances remains very superficial. Using direct neural recordings in humans, we have characterized complex SNS recruitment strategies, including i) modifications of firing rate of axons already recruited at baseline, ii) recruitment of additional neural populations during stress, and iii) variations in the timing of these axonal firing patterns. We now aim to improve our understanding of the mechanisms controlling these neural recruitment patterns as well as their interpretation by blood vessels as measured in their patterns of vasoconstriction.******Research Aims: 1) Determine the brain regions and possible neural control mechanisms associated with the specific SNA patterns, 2) Develop methods that manipulate these communication patterns in a titrated manner to study further the interactions between sensory and sympathetic neural systems, and 3) Quantify how SNA signals are interpreted by blood vessels in terms of the magnitude of vasoconstriction. Using a variety of physiological stressors, we will assess relationships between SNA action potential recruitment (microneurography), functional brain activation (neuroimaging), and muscle blood flow (ultrasound and diffusive correlative spectroscopy). These studies are highly novel and address a fundamental homeostatic principle that enhances animal survival through acute and chronic adaptations to stress.