Multiscale Imaging of Spontaneous Activity in Cortex: Mechanisms, Development and Function

皮层自发活动的多尺度成像：机制、发育和功能

• 批准号: 9266944
• 负责人: R Todd Constable
• 金额: $ 9.99万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9266944
• 关键词: Address; Animals; Area; Behavioral; Brain; Brain imaging; Cells; Cerebral cortex; Data; Dependence; Development; Disease model; Equilibrium; Functional Magnetic Resonance Imaging; Future; Health; Human; Image; Imaging Techniques; Individual; Interneurons; Investigation; Link; Measures; Methods; Microscopy; Modality; Modeling; Motor Cortex; Mus; Neocortex; Neurodevelopmental Disorder; Neurons; Neurosciences; Pattern; Peripheral; Pharmacogenetics; Photons; Play; Population; Resolution; Rest; Rodent; Role; Sensory; Signal Transduction; Source; Structure; System; Techniques; Technology; Testing; Time; Work; brain cell; calcium indicator; cell cortex; cellular imaging; design; imaging modality; improved; inhibitory neuron; innovation; innovative technologies; insight; interdisciplinary approach; network architecture; neural circuit; new technology; novel; optogenetics; relating to nervous system; response; self organization; sensory cortex; sensory gating; spatiotemporal; stem; tool; two-photon

 DESCRIPTION (provided by applicant): The purpose of this RFA is to promote the integration of experimental, analytic and theoretical capabilities for the examination of neural circuits and systems. This proposal is highly responsive to the RFA in that it links several different neuroscience labs to develop new technologies that provide for simultaneous multistate imaging and applies these technologies to the examination of how neuronal dynamics in mammalian cortex varies as a function of brain state and development. Paired imaging modalities will bridge the gap from imaging activity in individual neurons to whole brain circuit level analyses. The different scales will be linked with a comprehensive model such that each level of experimentation can inform the other. We will develop the technology to allow simultaneous single cell (two-photon) Ca2+ imaging of a local circuit and cortex-wide mesoscopic (single-photon) Ca2+ imaging across the entire neocortex. In separate paired studies in the same animals we will develop simultaneous mesoscopic Ca2+ imaging across the cortex with whole-brain functional MRI. Whole cortex mesoscopic Ca2+ imaging represents an innovative technology developed by one of the PIs (Crair) that uses mice expressing a genetically encoded Ca2+ indicator (GCaMP6) in all neurons or in select populations of neurons to allow both local neuronal and transcranial population level mesoscopic scale imaging across the cortex in the intact, unanesthetized developing mouse brain. This Ca2+ imaging technique will allow us to directly link single cell imaging to gross circuit level activity across the cortex and whole brain An integrative model is proposed to link these different modalities in order to understand the neural source of macroscopic circuit changes and the factors that influence this organization through development and as a function of behavioral brain state. This work is innovative in the novel Ca2+ imaging strategies to be further developed, and in the design of paired scale imaging to establish links between single neuron activity and circuit level organization. The work is significant in that it will provide a set of tools for detailed investigations of the impact of specific neuronal cell populations on brain circuit functional organization in healthy development and disease models. It is also significant in that new insights into the source and flow of neuronal activity will be obtained that will improve our understanding of the principles guiding self-organization in the developing brain and its dynamic modulation by brain state.

 描述（通过应用程序提供）：该RFA的目的是促进研究神经元电路和系统检查实验，分析和理论能力的整合。该建议对RFA的反应很高，因为它将几个不同的神经科学实验室联系起来开发了提供同时进行多层成像的新技术，并将这些技术应用于哺乳动物皮质中的神经元动力学如何作为脑状态和发育的函数的研究。配对的成像方式将弥合从单个神经元中的成像活性到整个大脑电路水平分析的差距。不同的量表将与一个综合模型相关，以便每个级别的实验可以告知对方。我们将开发该技术，以允许局部电路和整个新皮层的局部电路和范围范围的介质（单光子）Ca2+成像进行简单的单细胞（两光子）CA2+成像。在同一动物中的​​单独成对研究中，我们将使用全脑功能性MRI在皮层上同时进行中镜Ca2+成像。整个皮层介质CA2+成像代表了由PI（CRAIR）之一开发的创新技术，该技术使用在所有神经元中或精选神经元中表达一般编码的Ca2+指示剂（GCAMP6）的小鼠，允许局部神经元和trancranial severex severex tevers the Cortex跨越局部脑部介绍的局部神经元和tr量，均允许整个Cortex的脑海中的脑海中的尺度。这种CA2+成像技术将使我们能够直接将单细胞成像与整个皮质和整个大脑的总电路水平活动联系起来，提出了综合模型来连接这些不同的模态，以了解宏观电路变化的神经来源，以及通过发展和行为脑状态的功能来影响该组织的因素。这项工作在新型Ca2+成像策略中具有创新性，并在配对比例成像的设计中建立了单个神经元活动与电路级组织之间的联系。这项工作非常重要，因为它将提供一组工具，以详细研究健康发育和疾病模型中特定神经元细胞群对脑电路功能组织的影响。同样重要的是，将获得对神经元活性来源和流动的新见解，这将提高我们对指导发育中大脑中自我组织及其动态调节的原理的理解。