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Project 1

项目1

基本信息

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
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/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

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