Emergence of Functional Network Dynamics from Single Cell Properties

从单细胞特性中出现功能网络动力学

• 批准号: 10245166
• 负责人: Saul S Kato
• 金额: $ 39.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245166
• 关键词: Bacteria; Behavior; Biological; Brain; Caenorhabditis elegans; Calcium; Cells; Data; Engineering; Functional disorder; Genetic; Genomics; Goals; Image; Machine Learning; Maintenance; Microscopic; Microscopy; Modeling; Molecular; Motor output; Nervous system structure; Neurons; Pathology; Pattern; Property; Research; Resolution; Signal Transduction; Structure; Systems Analysis; Work; base; cell motility; dynamic system; image processing; nervous system disorder; novel strategies; signal processing; theories; therapeutic target

Project Summary/Abstract The collective dynamics of the network of neurons in the brain drive its primary holistic function — control of organismal behavior. Pathologies of the nervous system that disrupt this coordinated activity result in dysfunctional patterns of motor output and gross behavior. However, it is unknown how patterns of coordinated activity arise from the properties of single neurons and their connections. In the next five years we seek to develop a rigorous theory and biologically realistic model of the emergence of coordinated dynamics in a complete network of neurons, similar to the current level of understanding of how the dynamics of interacting molecular species produce goal-directed motile behavior in single-cell bacteria. We focus on the relatively simple nervous system of C. elegans; with precisely 302 neurons, it is a natural choice for such fundamental neurodynamical studies. To attack this problem, the research in our lab utilizes a fusion of experimental and computational approaches including advanced microscopy, genomic engineering, machine learning based image processing, quantitative behavior, and dynamical systems analysis. We have developed novel approaches to quantitatively probe and characterize the signal processing properties of single neurons as well as record and quantify the activity of the entire C. elegans nervous system at single-cell resolution using volumetric calcium imaging under genetic perturbation. We are now exploring the relationship between the microscopic properties of cellular signaling and the macroscopic function of collective network dynamics. A mechanistic model of the composition and maintenance of structured, controlled brain dynamics would provide a framework for understanding how gross neurological disease states arise from cellular and molecular dysfunction.

项目总结/文摘

项目成果

A set of hub neurons and non-local connectivity features support global brain dynamics in C. elegans.

一组中枢神经元和非局部连接功能支持线虫的全局大脑动力学。

• DOI: 10.1016/j.cub.2022.06.039
• 发表时间: 2022
• 期刊: Current biology : CB
• 作者: Uzel,Kerem;Kato,Saul;Zimmer,Manuel
• 通讯作者: Zimmer,Manuel