Project 1

项目摘要/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最先进的专业知识，结合 通过行为训练、电生理学和建模，研究软脑膜的基本方面 小鼠的神经血管回路。该电路由完全连接但不规则的软脑膜晶格组成 经历有节律振荡的小动脉 - 在 ~ 0.1 Hz 血管舒缩带内 - 隔离。皮尔电路 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，以产生 穿过皮质套的小动脉直径的相干振荡的动态模式。这些图案 包含频率略有不同的区域，即它们以部分反映 潜在的神经元输入。我们试图理解这种分割并对其进行建模，这很容易通过以下方式测量 光学和功能磁共振成像，并量化它如何定义大脑状态。 目标 1 旨在加深对软脑膜神经血管回路的基本生理学的理解。这个 包括测试脑小动脉是否真正充当非线性相互作用的振荡器，以便它们夹带和相位 锁定而不是被动过滤。在目标 2 中，我们探讨了打破之间锁定的竞争条件 振荡器，以便可以发生分割。这些实验得益于我们利用感官刺激的能力 不同的方式——触觉、视觉和听觉——每种方式都针对不同的大脑区域。他们也收获 来自我们驱动皮层下输入的能力，特别是那些涉及稳态大脑功能的输入，并使用 需要时直接光遗传学刺激。最后，这些实验受益于与 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 皮层范围内神经元兴奋性的控制。 该实验计划的灵感源自 Yoshiki 的相位耦合振荡器理论 仓本 1975 年的讲义。在这方面，目标 1 和 2 的进展与 项目4的理论工作。 目标 3 将软脑膜神经血管回路的动力学与穿透性神经血管的动力学联系起来。 小动脉；这些血管为薄壁组织提供能量基质。这些实验也在啮齿动物身上进行， 涉及使用 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 中直接测量氧气传输，这些数据为氧气计算提供输入 整个皮质地幔的张力。这反过来又提供了一种耦合 BOLD fMRI 和/或 CBV fMRI 的方法 软脑膜神经血管动力学。 总而言之，项目 1 的实验和分析将为推断当前的状态提供一种方法。 MR 成像的人类思维（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).