UCLA IDDRC: Cells, Circuits and Systems Core

加州大学洛杉矶分校 IDDRC：细胞、电路和系统核心

• 批准号: 10686887
• 负责人: HARLEY IAN KORNBLUM
• 金额: $ 15.29万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686887
• 关键词: 3-Dimensional; Acute; Animal Model; Bioinformatics; Biology; Brain; Calcium; Cell Culture Techniques; Cell model; Cells; Central Nervous System; Cerebrum; Comprehensive Cancer Center; DNA Sequence Alteration; Development; Disease; Disease model; Electroencephalography; Electrophysiology (science); Ethology; Flow Cytometry; Functional Imaging; Gene Expression; Genetic; Genomics; Human; Image; Intellectual and Developmental Disabilities Research Centers; Intellectual functioning disability; Methodology; Modeling; Molecular; Morphology; Mus; Mutation; Nervous System Physiology; Neurons; Organoids; Physiological; Pluripotent Stem Cells; Proxy; Rattus; Research; Research Personnel; Research Project Grants; Resource Sharing; Rodent; Role; Services; Slice; Stem Cell Research; System; Techniques; Therapeutic; Tissues; Training; Visualization; cell dimension; cell type; clinical translation; drug development; drug discovery; experimental study; human embryonic stem cell; human pluripotent stem cell; in vivo; induced pluripotent stem cell; nerve stem cell; neural; neurophysiology; novel; novel strategies; novel therapeutics; optogenetics; progenitor; screening; stem; stem cell derived tissues; stem cell technology; stem cells; tool

CORE D: Abstract The purpose of The Cells and Circuits Core is to provide investigators with tools needed to understand the cellular and physiological basis of intellectual and developmental disabilities (IDDs) and the role of potential therapeutics in IDD biology. Electrophysiological assessment is a vital to the understanding of both cellular and circuit alterations in models of IDD and cell culture is a vital tool in the understanding of cellular and molecular basis of ID. The core will consist of two components, the Neurophysiological Assessment component and the Cellular and Organoid Modeling component. In the Neurophysiological Assessment component, we will provide functional assessments at the cellular, circuit and systems level. The use of state-of-the-art electrophysiological approaches will aid IDDRC investigators in uncovering and understanding basic mechanisms causing the disorders being studied. These electrophysiological approaches consist of experiments performed in brain slices, acutely isolated neurons or cultures providing functional analyses of changes in neurons, local circuits and microcircuits induced primarily by genetic alterations in cellular, mouse or rat models. New techniques include optogenetics, EEG and local field potential (LFP) recording in vivo, and the use of miniscopes to image neuronal calcium transients in freely-behaving rodents to permit and facilitate analyses of developmental neurological functions at the cellular, circuit, and systems levels. In the Cellular and Organoid Modeling component, we will develop and provide models of IDD using human pluripotent stem cells, tissue-derived neural stem cells, and three-dimensional organoid cultures. Because human central nervous system cells are inherently different from rodent cells, we developed the facilities and capabilities to propagate and distribute them 2 cycles ago. In the previous cycle, we expanded the human cell core greatly, with a focus on pluripotent stem cell-derived cultures, including building the basis for the study of human cerebral organoids. We continue to provide these tools and expand our ability to deliver cells and expertise to ID researchers serving as a proxy to estimate neuronal activity in more ethological conditions. The use of stem cell technology provides a novel approach to modeling disease and developing rationale therapies based on utilization of human cells. The Core will provide facilities and expertise to propagate human embryonic stem cells (hESCs), induced pluripotent stem cells (hiPSCs), neural stem and progenitor and other cerebral cell types to create and study cellular models of IDD. A major function of the Core will be to aid investigators in culturing and studying cerebral organoids derived from hESCs and hiPSCs. In addition to its training and service functions, the Core will continue to develop novel methodologies in physiological assessment and human cell culture and analysis. The two components of the Core will interact seamlessly. The Core will interact regularly with the other Cores of the IDDRC and with the Research Project and will also aid investigators in drug discovery and development through interactions with Molecular Screening Shared Resource in the Broad Stem Cell Research and Jonsson Comprehensive Cancer Centers.

核心 D：摘要 细胞和电路核心的目的是为研究人员提供了解细胞和电路所需的工具 智力和发育障碍（IDD）的细胞和生理基础以及潜力的作用 IDD 生物学疗法。电生理学评估对于理解细胞和 IDD 和细胞培养模型中的电路改变是理解细胞和分子的重要工具 ID 的基础。核心将由两个部分组成：神经生理学评估部分和 细胞和类器官建模组件。在神经生理学评估部分，我们将提供 细胞、电路和系统级别的功能评估。使用最先进的电生理学技术 方法将帮助 IDDRC 调查人员发现和理解导致 正在研究的疾病。这些电生理学方法包括在脑切片中进行的实验， 精确分离的神经元或培养物，提供神经元、局部回路和神经元变化的功能分析 主要由细胞、小鼠或大鼠模型中的基因改变诱导的微电路。新技术包括 光遗传学、脑电图和局部场电位（LFP）体内记录，以及使用微型显微镜对神经元进行成像 自由行为的啮齿动物中的钙瞬变允许并促进发育神经学分析 在蜂窝、电路和系统级别发挥作用。在细胞和类器官建模组件中，我们将 使用人类多能干细胞、组织源性神经干细胞开发并提供 IDD 模型，以及 三维类器官培养物。因为人类中枢神经系统细胞本质上不同于 啮齿动物细胞，我们在两个周期前开发了繁殖和分发它们的设施和能力。在 上一个周期，我们极大地扩展了人类细胞核心，重点是多能干细胞衍生的培养物， 包括为人类大脑类器官的研究奠定基础。我们将继续提供这些工具并 扩大我们向 ID 研究人员提供细胞和专业知识的能力，作为估计神经元活动的代理 在更多的行为学条件下。干细胞技术的使用提供了一种疾病建模的新方法 并开发基于利用人体细胞的合理疗法。核心区将提供设施和 增殖人类胚胎干细胞（hESC）、诱导多能干细胞（hiPSC）、神经细胞的专业知识 干细胞和祖细胞以及其他脑细胞类型，用于创建和研究 IDD 细胞模型。一个主要功能是 核心将是帮助研究人员培养和研究源自 hESC 和 hiPSC 的大脑类器官。 除了培训和服务功能外，核心还将继续开发新的方法 生理评估和人体细胞培养和分析。核心的两个组件将相互作用 无缝地。该核心将定期与 IDDRC 的其他核心以及研究项目进行互动 还将通过与分子筛选的相互作用帮助研究人员进行药物发现和开发 Broad 干细胞研究中心和 Jonsson 综合癌症中心的共享资源。