Project 1

项目总结/摘要-项目1 我们建议利用我们在体内光学成像和数据分析方面的最先进的专业知识， 通过行为训练、电生理学和建模，研究软膜的基本方面， 小鼠的神经血管回路。这个电路是由一个完全连接的，虽然不规则的软膜晶格 在~ 0.1 Hz血管振荡带中进行节律性振荡的小动脉。软膜电路 整合来自邻近血管、底层神经元和皮层下区域的神经元活动， 穿过皮质套的小动脉直径的相干振荡的动态模式。这些模式 包含频率略有不同的区域，即，他们以一种部分反映 潜在的神经元输入我们试图理解和模拟这种分割，这是很容易衡量与 光学和功能磁共振成像，并量化它如何定义大脑状态。 目的1寻求制定一个理解的基本生理学软膜神经血管回路。这 包括测试大脑小动脉是否真的充当非线性相互作用的振荡器， 锁定而不是被动过滤。在目标2中，我们探讨了打破锁定的竞争条件， 振荡器，以便能够发生分块。这些实验得益于我们利用感官刺激的能力， 不同的方式-触摸，视觉和听觉-每一个针对不同的大脑区域。他们也获得 从我们驱动皮质下输入的能力，特别是那些涉及稳态大脑功能的输入， 在需要时直接进行光遗传学刺激。最后，这些实验从与 项目2的神经调节研究，因为皮层下神经调节提供了区域和 对神经元兴奋性的控制 实验计划的动机是相位耦合振荡器的理论，日期从Yoshiki 1975年，任本光教授。在这方面，目标1和目标2的进展与联合国的工作密切相关， 项目4的理论成果。 目的3将软脑膜神经血管回路的动力学与穿通的动力学联系起来 小动脉;这些血管为实质提供能量基质。这些实验也是在啮齿类动物身上进行的， 包括使用CBV fMRI和自适应光学双光子成像对大脑地幔进行深层成像。一起 在项目2中直接测量氧气输送，这些数据为计算氧气输送提供了输入数据。 整个皮质层的张力这反过来又提供了一种将BOLD fMRI和/或CBV fMRI 软脑膜神经血管动力学的联系 总而言之，项目1的实验和分析将提供一种前进的方式来推断 MR成像中的人类思维（项目3）。

PROJECT SUMMARY/ABSTRACT – PROJECT 1 We propose to leverage our state-of-the-art expertise in vivo optical imaging and data analysis, combined with behavioral training, electrophysiology, and modeling, to investigate fundamental aspects of the pial neurovascular circuit in mice. This circuit is composed of a fully connected albeit irregular lattice of pial arterioles that undergo rhythmic oscillations - in the ~ 0.1 Hz vasomotor band - in isolation. The pial circuit integrates neuronal activity from neighboring vessels, underlying neurons, and subcortical regions to produce dynamic patterns of coherent oscillations in arteriolar diameter across the cortical mantel. These patterns contain regions at slightly different frequencies, i.e., they parcellate, in a manner that partially reflects the underlying neuronal input. We seek to understand and model this parcellation, which is readily measured with optical and functional MR imaging, and quantify how it defines brain state. Aim 1 seeks to formulate an understanding of fundamental physiology of the pial neurovascular circuit. This includes testing if brain arterioles truly act as non-linear interacting oscillators, so that they entrain and phase lock rather than passively filter. In Aim 2 we explore the competitive conditions that break locking between oscillators so that parcellation can occur. These experiments gain from our ability to use sensory stimuli from different modalities - touch, vision and audition - each of which targets a different brain area. They also gain from our ability to drive subcortical inputs, particularly those involved in homeostatic brain function, and use direct optogenetic stimulation where needed. Lastly, these experiments gain from interaction with the neuromodulatory investigations of Project 2, as subcortical neuromodulation provides both regional and cortex-wide control of neuronal excitability. The experimental plan is motivated by the theory of phase-coupled oscillators that dates from Yoshiki Kuramoto's 1975 Lecture Notes. In this regard, progress on Aims 1 and 2 are strongly interwoven with the theory effort of Project 4. Aim 3 will connect the dynamics of the pial neurovascular circuit with the dynamics of the penetrating arterioles; these vessels source energy substrates to the parenchyma. These experiments, also in rodents, involve deep imaging of the cerebral mantel with CBV fMRI and adaptive optics two photon imaging. Together with direct measurements of oxygen transport in Project 2, these data provide input for calculations of oxygen tension throughout the cortical mantle. This, in turn, provides a means to couple BOLD fMRI and/or CBV fMRI to pial neurovascular dynamics. All told, the experimentation and analysis of Project 1 will provide a way forward to infer the state of the human mind from MR imaging (Project 3).