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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：该 RFA 的目的是促进神经回路和系统检查的实验、分析和理论能力的整合。该提案对 RFA 做出了高度响应，因为它将几个不同的神经科学实验室联系起来。开发提供同时多状态成像的新技术，并将这些技术应用于检查哺乳动物皮层的神经动力学如何随大脑状态和发育而变化，配对成像模式将弥合从单个神经元的成像活动到整个大脑的成像活动的差距。不同的尺度将与一个综合模型联系起来，以便每个级别的实验都可以相互告知。我们将开发允许对局部电路和皮层范围同时进行单细胞（双光子）Ca2+成像的技术。在同一动物的单独配对研究中，我们将通过全脑功能 MRI 开发同步介观 Ca2+ 成像。由其中一位 PI (Crair) 开发的创新技术，使用在所有神经元或选定的神经元群体中表达基因编码的 Ca2+ 指示剂 (GCaMP6) 的小鼠，以允许局部神经元和经颅群体水平的介观尺度成像穿过完整的皮质这种 Ca2+ 成像技术将使我们能够将单细胞成像与整个大脑皮层和整个大脑的总体回路水平活动直接联系起来。提出了一个综合模型来连接这些不同的模式。为了了解宏观回路变化的神经源以及通过发育影响该组织的因素以及行为大脑状态的函数，这项工作在待进一步开发的新型 Ca2+ 成像策略以及配对的设计方面具有创新性。这项工作意义重大，因为它将提供一套工具，用于详细研究特定神经元细胞群对健康发育和疾病模型中脑回路功能组织的影响。它还具有重要意义，因为对来源和流程有了新的见解我们将获得神经活动的详细信息，这将提高我们对发育中大脑的自组织指导原则及其受大脑状态的动态调节的理解。