Project 1
Project 1
批准号:
10294712
负责人:
David Kleinfeld
金额:
$58.76万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-08-16 至 2026-05-31
关键词:
AreaAuditoryAutomobile DrivingBRAIN initiativeBehavioralBloodBlood capillariesBlood flowBrainCaliberCerebrumCommunicationCortical ColumnCoupledDataData AnalysesElectrophysiology (science)Endothelial CellsEnergy-Generating ResourcesEquilibriumFrequenciesFunctional Magnetic Resonance ImagingG-BandingHomeostasisHumanImageIndividualInvestigationLateralLeadLengthMagnetic Resonance ImagingMeasurementMeasuresMedialMindModalityModelingMusNatureNeuronsOpticsOxygenPathway interactionsPatternPeriodicityPhasePhysiologicalPhysiologyPlayRodentRoleSamplingSensorySmooth MuscleStimulusSystemTestingTouch sensationTrainingVasomotorVibrissaeVisionWorkadaptive opticsarterioleexperimental studyin vivo optical imaginglecture notesmodel designmuscle formneuronal excitabilityneuroregulationneurovascularneurovascular couplingoptogeneticsoxygen transportprogramsresponsesensory inputsensory stimulusspatiotemporaltheoriestooltwo photon microscopytwo-dimensionaltwo-photonvasomotion
中文摘要
项目总结/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,
通过行为训练、电生理学和建模,研究软膜的基本方面,
小鼠的神经血管回路。这个电路是由一个完全连接的,虽然不规则的软膜晶格
在~ 0.1 Hz血管振荡带中进行节律性振荡的小动脉。软膜电路
整合来自邻近血管、底层神经元和皮层下区域的神经元活动,
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,他们以一种部分反映
潜在的神经元输入我们试图理解和模拟这种分割,这是很容易衡量与
光学和功能磁共振成像,并量化它如何定义大脑状态。
目的1寻求制定一个理解的基本生理学软膜神经血管回路。这
包括测试大脑小动脉是否真的充当非线性相互作用的振荡器,
锁定而不是被动过滤。在目标2中,我们探讨了打破锁定的竞争条件,
振荡器,以便能够发生分块。这些实验得益于我们利用感官刺激的能力,
不同的方式-触摸,视觉和听觉-每一个针对不同的大脑区域。他们也获得
从我们驱动皮质下输入的能力,特别是那些涉及稳态大脑功能的输入,
在需要时直接进行光遗传学刺激。最后,这些实验从与
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
对神经元兴奋性的控制
实验计划的动机是相位耦合振荡器的理论,日期从Yoshiki
1975年,任本光教授。在这方面,目标1和目标2的进展与联合国的工作密切相关,
项目4的理论成果。
目的3将软脑膜神经血管回路的动力学与穿通的动力学联系起来
小动脉;这些血管为实质提供能量基质。这些实验也是在啮齿类动物身上进行的,
包括使用CBV fMRI和自适应光学双光子成像对大脑地幔进行深层成像。一起
在项目2中直接测量氧气输送,这些数据为计算氧气输送提供了输入数据。
整个皮质层的张力这反过来又提供了一种将BOLD fMRI和/或CBV fMRI
软脑膜神经血管动力学的联系
总而言之,项目1的实验和分析将提供一种前进的方式来推断
MR成像中的人类思维(项目3)。
英文摘要
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).
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A web-based framework for multi-modal visualization and annotation of neuroanatomical data
-
批准号:10365435
-
项目类别:
-
资助金额:$163.45万
-
财政年份:2021
-
负责人:David Kleinfeld
-
依托单位:
Project 1
-
批准号:10470265
-
项目类别:
-
资助金额:$55.03万
-
财政年份:2021
-
负责人:David Kleinfeld
-
依托单位:
Project 1
-
批准号:10649643
-
项目类别:
-
资助金额:$86.76万
-
财政年份:2021
-
负责人:David Kleinfeld
-
依托单位:
Direct wavefront sensing and adaptive optics to enable two-photon imaging axons and spines throughout all of cortex
-
批准号:10640249
-
项目类别:
-
资助金额:$34.03万
-
财政年份:2019
-
负责人:David Kleinfeld
-
依托单位:
Direct wavefront sensing and adaptive optics to enable two-photon imaging axons and spines throughout all of cortex
-
批准号:10425220
-
项目类别:
-
资助金额:$34.01万
-
财政年份:2019
-
负责人:David Kleinfeld
-
依托单位:
Direct wavefront sensing and adaptive optics to enable two-photon imaging axons and spines throughout all of cortex
-
批准号:10021661
-
项目类别:
-
资助金额:$33.92万
-
财政年份:2019
-
负责人:David Kleinfeld
-
依托单位:
Imaging the molecular constituents of the brain vasculature and lymphatic connectome
-
批准号:10834499
-
项目类别:
-
资助金额:$10.0万
-
财政年份:2019
-
负责人:David Kleinfeld
-
依托单位:
Descending Control of Orofacial Behavior
-
批准号:10413916
-
项目类别:
-
资助金额:$54.98万
-
财政年份:2018
-
负责人:David Kleinfeld
-
依托单位:
Descending Control of Orofacial Behavior
-
批准号:10199076
-
项目类别:
-
资助金额:$54.93万
-
财政年份:2018
-
负责人:David Kleinfeld
-
依托单位:
Realization of Optical Cell-based Reporters for in vivo Detection of Neuropeptides
-
批准号:9213616
-
项目类别:
-
资助金额:$99.69万
-
财政年份:2016
-
负责人:David Kleinfeld
-
依托单位:
Resilient versus fragile aspects of blood flow in the mammalian brain
-
批准号:10318944
-
项目类别:
-
资助金额:$89.12万
-
财政年份:2016
-
负责人:David Kleinfeld
-
依托单位:
Resilient versus fragile aspects of blood flow in the mammalian brain
-
批准号:10523048
-
项目类别:
-
资助金额:$89.12万
-
财政年份:2016
-
负责人:David Kleinfeld
-
依托单位:
Resting state connectivity: Biophysical basis for and improved fMRI measurements
-
批准号:9353883
-
项目类别:
-
资助金额:$101.17万
-
财政年份:2016
-
负责人:David Kleinfeld
-
依托单位:
Resting state connectivity: Biophysical basis for and improved fMRI measurements
-
批准号:9206009
-
项目类别:
-
资助金额:$102.55万
-
财政年份:2016
-
负责人:David Kleinfeld
-
依托单位:
Resilient versus fragile aspects of blood flow in the mammalian brain
-
批准号:10063571
-
项目类别:
-
资助金额:$81.37万
-
财政年份:2016
-
负责人:David Kleinfeld
-
依托单位:
Ultra-large field two-photon microscope to image transcortical brain dynamics
-
批准号:8893665
-
项目类别:
-
资助金额:$21.76万
-
财政年份:2015
-
负责人:David Kleinfeld
-
依托单位:
Optogenetic mapping of synaptic activity and control of intracellular signaling
-
批准号:9128045
-
项目类别:
-
资助金额:$38.75万
-
财政年份:2014
-
负责人:David Kleinfeld
-
依托单位:
Optogenetic mapping of synaptic activity and control of intracellular signaling
-
批准号:8827155
-
项目类别:
-
资助金额:$38.75万
-
财政年份:2014
-
负责人:David Kleinfeld
-
依托单位:
Defining the Logic of Neurovascular Signaling in the Brain
-
批准号:8145277
-
项目类别:
-
资助金额:$76.5万
-
财政年份:2010
-
负责人:David Kleinfeld
-
依托单位:
Defining the Logic of Neurovascular Signaling in the Brain
-
批准号:8304980
-
项目类别:
-
资助金额:$76.73万
-
财政年份:2010
-
负责人:David Kleinfeld
-
依托单位:
海外基金