Project 1

项目1

基本信息

批准号：
10294712
负责人：
David Kleinfeld
金额：
$ 58.76万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
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/10294712
关键词：
Area Auditory Automobile Driving BRAIN initiative Behavioral Blood Blood capillaries Blood flow Brain Caliber Cerebrum Communication Cortical Column Coupled Data Data Analyses Electrophysiology (science)Endothelial Cells Energy-Generating Resources Equilibrium Frequencies Functional Magnetic Resonance Imaging G-Banding 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 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 sensory input sensory stimulus spatiotemporal theories tool two photon microscopy two-dimensional two-photon vasomotion

项目摘要

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由完全连接的不规则软脑膜网格组成。经历节律性振荡的小动脉 - 在 ~ 0.1 Hz 血管舒缩带内 - 孤立的软脑膜回路。整合邻近血管、底层神经元和皮层下区域的神经活动，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模式。包含频率略有不同的区域，即它们以部分反映我们寻求理解和建模这种分割，这可以很容易地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基本生理学的理解。包括测试脑小动脉是否真正充当非线性振荡器，以便它们夹带和相位在目标 2 中，我们探讨了打破锁定的竞争条件。这些实验受益于我们使用感官刺激的能力。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。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，并使用最后，这些实验从与光遗传学的相互作用中获益。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的神经兴奋性控制。该实验计划的灵感源自 Yoshiki 的相位耦合振荡器理论 Kuramoto 的 1975 年讲义在这方面，目标 1 和 2 的进展与目标密切相关。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；这些血管为实质提供能量底物这些实验也在啮齿类动物中进行。涉及使用 CBV fMRI 和自适应光学两光子成像对大脑地幔进行深层成像。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）。