Defining the Logic of Neurovascular Signaling in the Brain

摘要 血液是大脑中重要而有限的资源：神经元活动需要氧气供应， 葡萄糖，并且剥夺流向甚至受限区域的流动不可避免地导致细胞死亡。怎么样 血液的分布控制相对于不断变化的需求皮层？答案与 皮质功能在发育过程中，它们产生了血管结构的“设计规则”。从 从生理学的角度来看，这些答案定义了将神经元活动与变化联系起来的状态变量 血液流动。这对神经成像有影响，因为从血液中提取氧气是神经成像的关键。 BOLD fMRI的对比基础。最后，对于神经学来说，答案决定了 血管创伤和疾病的认知过程。 目前关于神经元和小动脉之间分子信号传导的文献，主要基于切片 指出扩张小动脉的血管活性信号分子之间的竞争 平滑肌和引起收缩的那些。这些信号分子的混合物被释放出来， 抑制性中间神经元直接接触肌肉，兴奋性神经元通过 包裹血管的星形胶质细胞的兴奋。这张照片是令人信服的，但不完整，因为自然 刺激在亚秒级上改变流动，而文献指出在数十秒上的改变。 主要的挑战是在体内测定信号分子和流动。我们会遇到这个 通过结合我们在体内电生理学和成像方面的优势， 精确定量血流和新设计的信号分子指标。 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了 变量，就像通道动力学形成单神经元动力学中的状态变量一样。这样的 模型将阐明神经血管疾病模型和神经影像学研究。

Abstract 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. Such a model will clarify neurovascular disease models and neuroimaging studies.