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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

基本信息

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
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/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

项目摘要

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.

项目摘要/摘要-总体