Project 1

项目摘要/摘要--项目1 我们计划利用我们在活体光学成像和数据分析方面的最先进专业知识，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。这个电路由一个完全相连但不规则的pial晶格组成。 在~0.1赫兹血管运动频段内经历节律性振荡的小动脉被隔离。该寻呼电路 整合邻近血管、下层神经元和皮质下区域的神经元活动，以产生 跨皮质壁台的小动脉直径内相干振荡的动态模式。这些模式 包含频率略有不同的区域，即它们以一种部分反映 潜在的神经元输入。我们试图理解和模拟这种分割，这是很容易用来衡量的 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试图形成对软脑膜神经血管回路的基本生理学的理解。这 包括测试脑小动脉是否真的充当非线性相互作用的振荡器，从而使它们缠绕和相变 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，这样就可以发生分裂。这些实验得益于我们利用感官刺激 不同的模式--触摸、视觉和听觉--每种模式都针对不同的大脑区域。他们也获得了 来自我们驱动皮质下输入的能力，特别是那些涉及大脑内平衡功能的输入，并使用 在需要的地方直接进行光遗传刺激。最后，这些实验从与 项目2的神经调节研究，因为皮质下神经调节提供区域和 大脑皮质对神经元兴奋性的控制。 该实验计划的动机是吉木提出的相位耦合振荡器理论。 仓本1975年的演讲笔记。在这方面，目标1和目标2的进展与 项目4的理论工作。 目标3将软脑膜神经血管环路的动力学与穿透的动力学联系起来。 小动脉；这些血管为实质提供能量底物。这些实验也是在啮齿动物身上进行的， 包括使用CBV功能磁共振成像和自适应光学双光子成像对大脑斗篷进行深度成像。同舟共济 在项目2中，通过直接测量氧气传输，这些数据为氧气的计算提供了输入 整个大脑皮层都处于紧张状态。这进而提供了一种将BOLD功能磁共振成像和/或CBV功能磁共振成像相结合的方法 软脑膜神经血管动力学。 综上所述，项目1的实验和分析将提供一种方法来推断 来自磁共振成像的人类大脑(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).