Local neuronal drive and neuromodulatory control of activity in the pial neurovascular circuit

软脑膜神经血管回路活动的局部神经元驱动和神经调节控制

• 批准号: 10470261
• 负责人: Anna Devor
• 金额: $ 277.48万
• 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/10470261
• 关键词: Adopted; Affect; Analog Computers; Area; Behavioral; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain region; Caliber; Cell Nucleus; Collaborations; Computing Methodologies; Coupled; Coupling; Data; Data Analyses; Data Collection; Detection; Education; Electroencephalography; Electrophysiology (science); Elements; Esthesia; Frequencies; Functional Magnetic Resonance Imaging; Generations; Homeostasis; Human; Image; Individual; Joints; Knowledge; Lead; Location; Locomotion; Logic; Magnetic Resonance Imaging; Mathematics; Measurement; Measures; Mechanics; Mediating; Microscopy; Modality; Modeling; Mus; Nature; Neuromodulator; Neurons; Neurosciences; Optics; Output; Oxygen; Pattern; Periodicity; Phase; Physiology; Process; Publications; Recording of previous events; Regulation; Resolution; Rest; Schools; Science; Signal Transduction; Smooth Muscle; Spinal; Structure; Technology; Testing; Theoretical Studies; Training; Vascular blood supply; Vasomotor; analytical method; arteriole; awake; base; central pattern generator; constriction; data acquisition; experimental study; fascinate; hemodynamics; human subject; in vivo; interest; network models; neuroregulation; neurovascular; neurovascular coupling; optical imaging; oxygen transport; relating to nervous system; spatiotemporal; theories; two-dimensional; vasomotion

PROJECT SUMMARY/ABSTRACT – OVERALL We seek to understand the nature of the pial neurovascular circuit, whose dynamics is characterized by ultralow frequency oscillations near 0.1 Hz that parcellate into separate coherent regions across cortex. We will use this knowledge to form a mathematical relation between the hemodynamic patterns observed in optical and functional magnetic resonance imaging experiments and the underlying brain state. Our proposed studies propose to leverage our experimental expertise in in vivo optical microscopy in mouse and fMRI in mouse and human. These primary modalities for data acquisition are combined with behavioral training, electrophysiology, and data analysis. Our experimental effort is parallel by two theoretical efforts. One mixed analytical/computational effort is on coupled oscillator dynamics to formulate models, at varying levels of complexity, of the pial neurovascular circuit. A second solely computational effort concerns the modulation of the transport of oxygen, by regional oscillations of the pial neurovascular circuit. The pial neurovascular circuit is composed of a two-dimensional network of pial arterioles that undergo rhythmic oscillations in the ~ 0.1 Hz vasomotor band. Each element in this circuit - a segment of arteriole whose diameter is modulated by the constriction/dilation of smooth muscle, contains an intrinsic rhythm generator, much like intrinsic bursting neurons in central pattern generators. The pial arterioles integrate neuronal activity from neighboring arterioles, underlying neurons, subcortical neurons, and neuromodulatory centers to produce dynamic patterns of coherent oscillations in arteriolar diameter across the cortical mantle. These patterns contain regions that oscillate at slightly different frequencies, i.e., they parcellate into separate regions. The fascinating issue is that the parcellation only partially reflects input from the directly underlying neuronal input. We seek to understand, model, and exploit this parcellation. The PIs have collaborated on issues in neuroscience and neurovascular science for many years. This proposal is a result of their discoveries and converging interest in a structured collaborative effort. Project 1 will formulate an understanding of fundamental physiology of the pial neurovascular circuit. This includes determining if brain arterioles truly act as interacting non-linear oscillators, i.e., that they entrain and phase-lock rather than passively filter. Projects 1, 2, and 4 will explore experimentally and theoretically how four competitive interactions, viz, input from neighboring arterioles, (ii) input from underlying neurons, (iii) input from subcortical areas involved in homeostasis; and (iv) input from brain neuromodulatory centers, lead to the observed patterns of pial neurovascular activity. Projects 2 and 4 will explore and model the regulation of oxygen in subsurface vessels, while Project 3 will expand the resolution of MR imaging in humans to observe single vessels CBV changes and thus measure pial neurovascular dynamics with unparalleled resolution. A particular interest is to transform spatiotemporal patterns of vasomotion into predictions of internal brain state.

项目概要/摘要——总体 我们试图了解软脑膜神经血管回路的性质，其动力学特征为 接近 0.1 Hz 的超低频振荡，在整个皮层中分割成单独的相干区域。我们将 利用这些知识来形成光学观察到的血流动力学模式之间的数学关系 和功能磁共振成像实验以及潜在的大脑状态。 我们提出的研究建议利用我们在体内光学显微镜方面的实验专业知识 小鼠以及小鼠和人类的功能磁共振成像。这些数据采集的主要方式与 行为训练、电生理学和数据分析。我们的实验工作与两个理论工作并行 努力。一项混合分析/计算工作是研究耦合振荡器动力学来制定模型， 软脑膜神经血管回路的复杂程度不同。第二个单独的计算工作涉及 通过软脑膜神经血管回路的局部振荡来调节氧气的输送。 软脑膜神经血管回路由软脑膜小动脉的二维网络组成，这些小动脉经历 约 0.1 Hz 血管舒缩带的节律振荡。该回路中的每个元件 - 一段小动脉 其直径由平滑肌的收缩/扩张调节，包含内在节律 发生器，很像中枢模式发生器中的内在爆发神经元。软脑膜小动脉整合 来自邻近小动脉、底层神经元、皮层下神经元和神经调节的神经元活动 中心产生穿过皮质地幔的小动脉直径的相干振荡的动态模式。 这些模式包含以稍微不同的频率振荡的区域，即，它们分割成单独的 地区。令人着迷的问题是，分割仅部分反映了直接底层的输入 神经元输入。我们寻求理解、建模和利用这种分割。 PI 多年来一直在神经科学和神经血管科学问题上进行合作。这 提案是他们的发现和对结构化协作努力的共同兴趣的结果。项目1将 了解软脑膜神经血管回路的基本生理学。这包括 确定脑小动脉是否真正充当相互作用的非线性振荡器，即它们夹带和锁相 而不是被动地过滤。项目 1、2 和 4 将通过实验和理论上探索四个 竞争性相互作用，即来自邻近小动脉的输入，（ii）来自底层神经元的输入，（iii）来自 参与体内平衡的皮层下区域； (iv) 来自大脑神经调节中心的输入，导致 观察软脑膜神经血管活动的模式。项目 2 和 4 将探索并模拟监管 地下血管中的氧气，而项目 3 将扩大人类 MR 成像的分辨率以观察 单血管 CBV 变化，从而以无与伦比的分辨率测量软脑膜神经血管动力学。一个 特别感兴趣的是将血管舒缩的时空模式转化为对大脑内部状态的预测。