Astrocyte Modulation of Neural Circuit Function and Behavior

星形胶质细胞对神经回路功能和行为的调节

基本信息

批准号：
10693161
负责人：
Cagla Eroglu
金额：
$ 223.12万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
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：
2021-08-15 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10693161
关键词：
Address Anatomy Astrocytes Atlases Behavior Behavioral Assay Biology Brain Brain region Collaborations Communication Communities Complex Computer Models Data Data Analyses Data Science Core Disease Elements Environment Gene Expression Goals Health Heterogeneity Human Intervention Link Machine Learning Mediating Methods Modeling Modernization Molecular Molecular Analysis Molecular Genetics Morphology Neuroglia Neuromodulator Neurons Neurosciences Neurotransmitters Output Perception Play Protein Engineering Research Personnel Research Project Grants Rewards Role Scientist Signal Transduction Statistical Data Interpretation Structure Supporting Cell Synapses System Techniques Testing Theoretical model Time brain research cell type cellular imaging computerized tools experience experimental analysis gene therapy genetic analysis genetic profiling in vivo imaging information processing innovation learned behavior mathematical model molecular dynamics molecular imaging multidisciplinary nervous system development neural neural circuit neuronal circuitry neuroregulation neurotransmission novel operation predictive modeling programs spatial integration synaptic function theories tool tool development

项目摘要

Project Summary: Overall “What is the function of glial cells in neural centers? The answer is still not known, and it may remain unsolved for many years to come until scientists find direct methods to attack it.” (Ramon y Cajal, 1901). This prophecy turned out to be accurate. Astrocytes, one of the most abundant cell types in the brain, have long been thought of as primarily passive support cells. Over the past two decades, studies indicate that astrocytes play pivotal roles in nervous system development, function, and diseases. However, a major unresolved issue in neuroscience is how astrocytes integrate diverse neuronal signals under healthy conditions, modulate neural circuit structure and function at multiple temporal and spatial scales, and how aberrant excitation and molecular output influences sensorimotor behavior and contributes to disease. The overall goal of this U19 Team-Research BRAIN Circuit Program proposal is to address this fundamental issue by developing a deeper mechanistic understanding of astrocytes’ roles in neural circuit operation, complex behaviors, and brain computation theories. Two overarching questions will be addressed: 1) How do astrocytes temporally and spatially integrate molecular signals from the diverse types of local and projection neurons activated during sensorimotor behaviors. 2) How do astrocytes convert this information into functional outputs that modulate neural circuit structure and function at different spatial and temporal scales. A multidisciplinary, comprehensive effort is proposed to address these questions that can only be completed through close collaboration between researchers with unique and complementary expertise. An innovative multi-scale approach integrating functional, anatomical, and genetic analyses with theoretical modeling will be leveraged. This approach involves quantitative behavioral assays, large-scale imaging of cellular and molecular dynamics, targeted cell-type-specific manipulations, high- throughput omic techniques, genetic profiling, protein engineering, machine learning, and computational modeling. By integrating experimental and theoretical approaches, molecular, cellular, and circuit mechanisms will be determined through which astrocytes influence neural circuits and contribute to complex behaviors and brain computation theories. The experimental and data analysis tools developed as part of this project will be invaluable for the broader neuroscience community.

项目摘要：总体 “神经中心中神经胶质细胞的功能是什么？答案仍不知道，并且可能仍未解决多年来，直到科学家找到直接攻击它的方法。”（Ramon Y Cajal，1901年）。这一预言原来是准确的。星形胶质细胞是大脑中最丰富的细胞类型之一，长期以来一直被认为 AS主要被动支持细胞。在过去的二十年中，研究表明星形胶质细胞发挥着关键作用在神经系统发育，功能和疾病中的作用。但是，在神经科学是星形胶质细胞在健康条件下整合潜水员神经元信号的方式，调节神经元电路结构和功能在多个临时和空间尺度上，以及令人兴奋和分子的异常输出会影响感觉运动行为并导致疾病。这项U19团队研究的总体目标脑电路计划的建议是通过开发更深层的机理来解决这个基本问题了解星形胶质细胞在神经电路操作，复杂行为和大脑计算中的作用理论。将解决两个总体问题：1）星形胶质细胞如何临时和空间整合在感觉运动行为过程中激活的潜水员类型的局部和投影神经元的分子信号。 2）星形胶质细胞如何将这些信息转换为调节神经电路结构和的功能输出在不同的空间和临时尺度上发挥作用。提出了多学科的全面努力来解决这些问题只能通过具有独特和独特的研究人员之间的密切合作来完成完全专业知识。一种创新的多尺度方法，以整合功能，解剖和遗传将利用理论建模的分析。这种方法涉及定量行为测定，细胞和分子动力学的大规模成像，靶向细胞类型的操作，高 - 吞吐量的奥米技术，基因分析，蛋白质工程，机器学习和计算造型。通过整合实验和理论方法，分子，细胞和电路机制将确定星形胶质细胞会影响神经循环，并有助于复杂的行为和大脑计算理论。作为该项目的一部分开发的实验和数据分析工具将是对于更广泛的神经科学社区来说是无价的。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multiplex translaminar imaging in the spinal cord of behaving mice.

DOI：
10.1038/s41467-023-36959-2
发表时间：
2023-03-21
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Shekhtmeyster, Pavel;Carey, Erin M.;Duarte, Daniela;Ngo, Alexander;Gao, Grace;Nelson, Nicholas A.;Clark, Charles L.;Nimmerjahn, Axel
通讯作者：
Nimmerjahn, Axel

Data science and its future in large neuroscience collaborations.

DOI：
10.1101/2024.03.20.585936
发表时间：
2024-03-25
期刊：
bioRxiv
影响因子：
0
作者：
Schottdorf，Manuel;Yu，Guoqiang;Walker，Edgar Y.
通讯作者：
Walker，Edgar Y.

Astrocyte regulation of neural circuit function and animal behavior.

星形胶质细胞对神经回路功能和动物行为的调节。

DOI：
10.1002/glia.24223
发表时间：
2022
期刊：
Glia
影响因子：
6.2
作者：
Nimmerjahn,Axel;Hirrlinger,Johannes
通讯作者：
Hirrlinger,Johannes

Trans-segmental imaging in the spinal cord of behaving mice.

行为小鼠脊髓的跨节段成像。

DOI：
10.1038/s41587-023-01700-3
发表时间：
2023
期刊：
Nature biotechnology
影响因子：
46.9
作者：
Shekhtmeyster,Pavel;Duarte,Daniela;Carey,ErinM;Ngo,Alexander;Gao,Grace;Olmstead,JackA;Nelson,NicholasA;Nimmerjahn,Axel
通讯作者：
Nimmerjahn,Axel

A perspective on astrocyte regulation of neural circuit function and animal behavior.