Defining the Logic of Neurovascular Signaling in the Brain

描述 摘要： 确定脑血中神经血管信号的逻辑是大脑中一种重要而有限的资源：神经元活动需要氧气和葡萄糖的供应，而剥夺了即使是受限区域的流量也不可避免地会导致细胞死亡。相对于不断变化的皮质需求，血液的分布是如何被控制的？答案直接关系到大脑皮层的功能。从发展的角度来看，它们产生了血管结构的“设计规则”。从生理学的角度来看，答案定义了将神经元活动与血流变化联系起来的状态变量。这对神经成像有影响，因为从血液中提取氧气是BOLD功能磁共振成像对比度的基础。最后，对于神经学来说，答案决定了认知过程对血管损伤和疾病的抵抗力。目前关于神经元和小动脉之间的分子信号传递的文献主要基于切片准备，指出扩张小动脉平滑肌的血管活性信号分子和引起收缩的血管活性信号分子之间存在竞争。这种信号分子的混合物由直接接触肌肉的抑制性中间神经元和通过包裹血管的星形胶质细胞兴奋而起作用的兴奋性神经元释放。这幅图令人信服，但并不完整，因为自然刺激的变化是在亚秒级流动的，而文献指出的变化是几十秒。主要的挑战是分析信号分子和体内流动。我们将通过将我们在体内电生理学和成像方面的优势与我们精确量化血流的方法和新设计的信号分子指示器结合起来，迎接这一挑战。我们设想了一种神经血管控制模型，该模型将不同神经元亚型的活动映射到血管张力的变化。潜在信号分子的动力学形成状态变量，就像通道动力学形成单个神经元动力学中的状态变量一样。

DESCRIPTION Abstract: Defining the Logic of Neurovascular Signaling in the Brain Blood is a vital and limited resource in the brain: neuronal activity requires supplies of oxygen and glucose, and deprivation of flow to even restricted regions leads inevitably to cell death. How is the distribution of blood controlled relative to the changing needs of cortex? The answers bear directly on cortical function. Developmentally, they yield "design rules" for vascular architecture. From the perspective of physiology, the answers define state variables that relate neuronal activity to changes in blood flow. This has implications for neuroimaging, as the extraction of oxygen from blood is the basis of contrast in BOLD fMRI. Lastly, for neurology, the answers determine the resistance of cognitive processes to vascular trauma and disease. The current literature on molecular signaling between neurons and arterioles, based mainly on slice preparations, points to a competition between vasoactive signaling molecules that dilate arteriole smooth muscle and those that cause constriction. Mixtures of such signaling molecules are released by inhibitory interneurons, which directly contact muscle, and by excitatory neurons, which act via the excitation of astrocytes that encapsulate vessels. This picture is compelling yet incomplete, as natural stimuli change flow on the subsecond level while the literature points to changes on tens of seconds. The main challenge is to assay both signaling molecules and flow in vivo. We will meet this challenge by combining our strengths in in vivo electrophysiology and imaging with our methods for precise quantification of blood flow and newly engineered indicators for signaling molecules. We envision a model of neurovascular control that maps the activity of different neuronal subtypes to changes in vascular tone. The dynamics of the underlying signaling molecules form the state variables, much as channel dynamics form the state variables in single neuron dynamics.