Development and Divergence of Whole-Brain Activity

全脑活动的发展和分化

• 批准号: 10417604
• 负责人: Vivek Venkatachalam
• 金额: $ 47.34万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-05 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417604
• 关键词: Adult; Affect; Age; Animal Behavior; Animals; Behavior; Biological Models; Brain; Brain imaging; Caenorhabditis elegans; Calcium; Cells; Chemicals; Collection; Complement; Cues; Development; Funding; Gene Expression; Genetic; Goals; Housing; Human; Image; Individual; Larva; Learning; Maps; Measurement; Measures; Microfluidic Microchips; Microfluidics; Modeling; Molting; Motor Neurons; National Institute of Neurological Disorders and Stroke; Neurons; Newborn Infant; Optics; Output; Pattern; Process; Resolution; Sensory; Series; Stimulus; Structure; Synapses; System; Techniques; Touch sensation; Work; cell type; computerized tools; connectome; expectation; fictional works; individual variation; insight; inter-individual variation; lithography; nutrition; reproductive; response; tool; young adult; Adult; Affect; Age; Animal Behavior; Animals; Behavior; Biological Models; Brain; Brain imaging; Caenorhabditis elegans; Calcium; Cells; Chemicals; Collection; Complement; Cues; Development; Funding; Gene Expression; Genetic; Goals; Housing; Human; Image; Individual; Larva; Learning; Maps; Measurement; Measures; Microfluidic Microchips; Microfluidics; Modeling; Molting; Motor Neurons; National Institute of Neurological Disorders and Stroke; Neurons; Newborn Infant; Optics; Output; Pattern; Process; Resolution; Sensory; Series; Stimulus; Structure; Synapses; System; Techniques; Touch sensation; Work; cell type; computerized tools; connectome; expectation; fictional works; individual variation; insight; inter-individual variation; lithography; nutrition; reproductive; response; tool; young adult

Project Summary/Abstract An animal’s brain consists of interconnected neurons that are responsible for processing sensory information over many timescales to guide behavior. The function of that brain is determined partially by the animal’s connectome – the topology, strength, and valence of every connection in its brain. While a draft of the whole connectome for an animal (the worm Caenorhabditis elegans) has been available for decades, recent work has found that this connectome varies dramatically through development and between individuals. It is not stereotyped as expected. We do not know how this large variability in connectivity manifests itself in brain activity through development or between individuals. Nonetheless, the single connectome an animal has must somehow be able to support every behavior that the animal may perform in a given instant. Each of these behaviors may engage overlapping portions of the brain. This project aims to leverage calcium imaging to study how whole-brain activity in C. elegans varies through development and between individuals. Our goal is to clarify precisely how large-scale structure and function are related in a simple system. To do this, we will perform whole-brain imaging with cellular resolution in a collection of behaving individual animals as they progress from newly-hatched larvae through a series of molts and turn into adults. These long-term calcium recordings will be complemented by microfluidic measurements of whole-brain responses to chemosensory cues at multiple developmental stages. Throughout this process, we will focus on the following big questions: (1) How does the activity of every neuron in a worm change through development? (2) How does brain activity vary between genetically identical individuals? (3) How are each of the above questions affected by changes in environmental context? (4) How does the relationship between brain activity and connectivity change over development, and how does it vary between individuals? If successful, this work could provide unprecedented insight into how brain function changes as an animal adds neurons, connections, and synapses. It will show how inter-individual and intra-individual variation are related to the brain’s connectome. This will have immediate value in guiding expectations about how brain activity and brain wiring are related in other model systems and humans, where direct information about wiring is less readily available.

项目摘要/摘要 动物的大脑由互连的神经元组成，这些神经元负责处理感官信息 许多时间尺度指导行为。该大脑的功能由动物的连接部分部分决定 - 大脑中各个连接的拓扑，强度和价。而整个Connectome的草稿 几十年 连接组通过开发和个人之间的大幅变化。它不是预期的刻板印象。 我们不知道这种连通性的大变异性如何通过开发在大脑活动中表现出来 或个人之间。但是，动物必须以某种方式支持的单一连接组 动物在给定的瞬间可能会执行的每种行为。这些行为中的每一个都可能使重叠 大脑的部分。 该项目旨在利用钙成像来研究秀丽隐杆线虫中的全脑活动如何通过 发展和个人之间。我们的目标是精确澄清结构和功能的大规模结构和功能 与简单系统相关。为此，我们将在A中使用细胞分辨率执行全脑成像 从新轴幼虫发展到一系列蜕皮时，行为单个动物的收集 并变成成年人。这些长期钙记录将通过微流体测量完成 在多个发育阶段对化学感应线索的全脑反应。通过这个过程，我们 将关注以下大问题：（1）蠕虫中每个神经元的活动如何通过 发展？ （2）大脑活性在遗传相同的个体之间有何不同？ （3）每个 上述问题受环境环境变化影响？ （4）大脑之间的关系如何 活动和连通性在发展上的变化，个人之间的变化如何？ 如果成功，这项工作可能会为大脑功能如何变化作为动物提供前所未有的见解 添加神经元，连接和突触。它将显示个人间和个体内部变化是多么 与大脑的连接组有关。这将在指导有关大脑活动的期望时具有直接的价值 在其他模型系统和人类中，有关接线的直接信息较少 随时可用。