Project 1

项目1

• 批准号: 10649643
• 负责人: David Kleinfeld
• 金额: $ 86.76万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649643
• 关键词: Area; Auditory; Automobile Driving; BRAIN initiative; Behavioral; Blood; Blood capillaries; Blood flow; Brain; Cerebrum; Communication; Cortical Column; Coupled; Data; Data Analyses; Diameter; Electrophysiology (science); Endothelial Cells; Energy-Generating Resources; Equilibrium; Frequencies; Functional Magnetic Resonance Imaging; Homeostasis; Human; Image; Individual; Investigation; Lateral; Lead; Length; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mind; Modality; Modeling; Mus; Nature; Neurons; Optics; Oxygen; Pathway interactions; Pattern; Penetration; Periodicity; Phase; Physiological; Physiology; Play; Rodent; Role; Sampling; Sensory; Smooth Muscle; Stimulus; System; Testing; Touch sensation; Training; Vasomotor; Vibrissae; Vision; Work; adaptive optics; arteriole; experimental study; in vivo optical imaging; lecture notes; model design; muscle form; neuronal excitability; neuroregulation; neurovascular; neurovascular coupling; optogenetics; oxygen transport; programs; response; segregation; sensory stimulus; spatiotemporal; theories; tool; two photon microscopy; two-dimensional; two-photon; vasomotion

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).

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的最先进的专业知识，合并 通过行为训练，电生理学和建模，研究了PIAL的基本方面 小鼠的神经血管电路。该电路是由完全连接的，尽管是不规则的晶格 经历有节奏振荡的动脉 - 在〜0.1 Hz血管舒缩条带中 - 分离。 pial电路 整合来自相邻血管，潜在神经元和皮层下区域的神经元活性以产生 在皮质壁炉架上的小动脉直径相干振荡的动态模式。这些模式 包含略有不同频率的区域，即它们的区域，以部分反映的方式 基础神经元输入。我们试图理解和建模这种分析，很容易测量 光学和功能性MR成像，并量化其定义大脑状态的方式。 AIM 1旨在提出对PIAL神经血管回路基本生理学的理解。这 包括测试脑小动物是否真正充当非线性相互作用振荡器，以便它们进入和相位 锁定而不是被动过滤。在AIM 2中，我们探讨了竞争条件破裂的条件 振荡器可以发生分析。这些实验从我们使用感官刺激的能力中获得 不同的方式 - 触摸，视觉和试听 - 每个方式都针对不同的大脑区域。他们也获得了 从我们驱动皮层输入的能力，尤其是参与稳态脑功能的能力，并使用 在需要时直接进行光遗传刺激。最后，这些实验从与 皮质下神经调节的神经调节研究2既提供区域和 整个皮质的神经元控制。 实验计划是由Yoshiki的相耦合振荡器的理论激励的 库拉莫托（Kuramoto）的1975年讲义。在这方面，目标1和2的进展与 项目4的理论努力。 AIM 3将连接pial神经血管电路的动力学与穿透力的动力学 小动脉；这些容器将能量基板源为副群。这些实验，也在啮齿动物中 涉及使用CBV fMRI和自适应光学元件进行两种光子成像的大脑壁炉架的深度成像。一起 通过直接测量项目2中的氧运输，这些数据为氧计算提供了输入 整个皮质地幔的张力。反过来，这提供了一种大胆fMRI和/或CBV fMRI的手段 进行皮肤神经血管动力学。 总而言之，项目1的实验和分析将提供推断状态的前进的道路 MR成像的人类思想（项目3）。