BRAIN EAGER: Functional dynamics of whole brain activity, behavior, and development from birth to adulthood

大脑渴望：从出生到成年的整个大脑活动、行为和发育的功能动态

• 批准号: 1452593
• 负责人: Aravinthan D Samuel
• 金额: $ 30万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-15 至 2019-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1452593&HistoricalAwards=false
• 关键词: BRAIN; EAGER; Functional; dynamics; whole

From birth to adulthood, the brain and nervous system continuously expand and develop to keep up with the growing body. Neurons and connections must constantly be added or changed for any animal, including humans, to gain new behaviors or retain old ones. This project is to develop and apply technology to monitor brain and behavior from birth to adulthood of the roundworm C. elegans, an important and widely studied model for neuroscience. A controlled environment will be created where individual animals are born, roam freely, and grow to adulthood while a microscope continuously scans the activity patterns of every neuron in the worm's nervous system. Because of their rapid maturation (2 days) and small nervous system (302 neurons), the technology will be used to answer fundamental questions about the developing brain. For example, how do highly conserved behavioral patterns like forward and reverse movement emerge from a nervous system that adapts to a body that grows ten-fold from birth to adult? Coordinating the parallel development of brain, body, and behavior is a problem faced by all animals. The accessibility of C. elegans will yield the first comprehensive measurements of brain and behavior development in any animal. Bringing together developmental biology, neurophysiology, and neurotechnology will train young scientists who will work at the rich interface between the physical and life sciences.A system will be developed-- a motorized, rotating agar-coated ball-- upon which a nematode can freely move without interruption as it feeds, grows, molts through four larval stages, and becomes an adult. Throughout the nematode's life, the system will record the activity of the entire nervous system visualized throughout its optically transparent body using a confocal microscope that achieves video-rate volumetric recording. These experiments will provide unprecedented datasets that describe the behavioral life history of an individual animal in temporal correlation with whole brain activity patterns. Comparison of these rich datasets between wild-type animals and informative mutants will allow dissection of a wide range of interconnected and shared processes in neurodevelopment, regulation, learning, and memory. For example, understanding the developmental progression of the motor circuit will be achieved by obtaining circuit-wide measurements that describe how the 20-neuron motor circuit that drives the forward and backward movements of the 0.1-mm long juvenile worm is expanded into the 80-neuron motor circuit that drives the same movements of the 1-mm long adult. These studies will illuminate system-wide changes in the nervous system as it dynamically keeps up with animal growth.

从出生到成年，大脑和神经系统不断扩展和发展，以跟上不断增长的身体。对于任何动物，包括人类，神经元和连接都必须不断增加或改变，以获得新的行为或保留旧的行为。本计画旨在发展及应用技术，以监测蛔虫C从出生到成年的脑部及行为。elegans，一个重要的和广泛研究的模型神经科学。将创造一个受控的环境，在那里个体动物出生，自由漫游，并成长到成年，而显微镜不断扫描蠕虫神经系统中每个神经元的活动模式。由于其快速成熟（2天）和小神经系统（302个神经元），该技术将用于回答有关发育中大脑的基本问题。例如，一个神经系统如何适应一个从出生到成年增长了十倍的身体，那么像向前和向后运动这样高度保守的行为模式是如何产生的呢？协调大脑、身体和行为的平行发展是所有动物都面临的问题。C.线虫将首次对动物的大脑和行为发育进行全面的测量。将发育生物学、神经生理学和神经技术结合在一起，将培养年轻的科学家，他们将在物理科学和生命科学之间的丰富界面上工作。将开发一个系统--一个机动的、旋转的琼脂涂层球--线虫可以在上面自由移动，不受干扰地进食、生长、蜕皮，经历四个幼虫阶段，然后变成成虫。在线虫的整个生命过程中，该系统将使用共聚焦显微镜记录整个神经系统的活动，该系统通过其光学透明的身体可视化，实现视频速率体积记录。这些实验将提供前所未有的数据集，描述个体动物的行为生活史与整个大脑活动模式的时间相关性。野生型动物和信息突变体之间的这些丰富的数据集的比较将允许解剖神经发育，调节，学习和记忆中的广泛的相互关联和共享的过程。例如，了解运动回路的发育进程将通过获得回路范围的测量来实现，这些测量描述了驱动0.1 mm长的幼年蠕虫的向前和向后运动的20个神经元运动回路如何扩展到驱动1 mm长的成年蠕虫的相同运动的80个神经元运动回路。这些研究将阐明神经系统的全系统变化，因为它动态地跟上动物的生长。