3D Digital Modeling of the Developing Drosophila Brain

发育中的果蝇大脑的 3D 数字建模

基本信息

批准号：
8604636
负责人：
VOLKER HARTENSTEIN
金额：
$ 32.68万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8604636
关键词：
Address Adult Animals Atlases Autistic Disorder Axon Behavior Control Bioinformatics Biological Neural Networks Brain Brain Part Caliber Cognition Communities Complex Computer software Data Data Set Dendrites Development Disease Drosophila genus Electron Microscopy Electronics Elements Embryo Exhibits Fascicle Funding Genes Genetic Grant Image Individual Learning Light Maps Memory Mental disorders Modeling Mushroom Bodies Neurites Neurobiology Neurons Pharmacological Treatment Population Prefrontal Cortex Process Relative (related person)Research Schizophrenia Staging Stereotyping Surface Synapses Technology Testing Time Vertebral column area striata base data mining digital digital models improved insight interest knowledge base motor control mutant nerve stem cell neural circuit neuroblast neuronal cell body public health relevance reconstruction relating to nervous system software development tool

项目摘要

DESCRIPTION (provided by applicant): Brains contain large number of neurons whose connections, formed by axonal and dendritic processes, are the structural underpinning of electrical circuits that control behavior. The analysis of circuits is of great importance. All acts of fine motor control, memory formation and cognition can only be understood if the circuitry within the brain compartments dealing with these functions is known. Likewise, the insight into psychiatric disease mechanisms and their pharmacological treatment requires brain circuitry to be known in detail. For example, recent findings suggest that diseases like autism or schizophrenia can be understood in terms of abnormalities in the micro- circuitry of the prefrontal cortex. We propose in this grant to develop and utilize bioinformatics tools that enable us to address circuitry in the Drosophila brain. The Drosophila central brain is formed by a stereotyped set of approximately 100 paired lineages, each one derived from one neuroblast. Neurons of one lineage form processes that spread within discrete compartments of the brain. Lineages thereby represent the most appropriate structural/developmental units of brain macro-circuitry. Reconstructing the projection of all lineages means to have generated an accurate map of Drosophila brain circuitry at the level of neuron populations ("macro-circuitry"). We propose to generate this map, presented in a standardized electronic format that is accessible to the neurobiology community. In addition, we will reconstruct circuitry at the level of individual synapses ("micro-circuitry"), which requires electron microscopy (EM). We have developed the software required for the automated recording, registration and navigation of large EM image data sets. We will further improve and use these tools to generate a digital EM dataset that, for the first time, encompasses the entire brain of an animal with a sizeable number of structurally complex neurons. Our software allows us to efficiently reconstruct the neural networks encountered in different parts of the brain. We anticipate that we will be able to learn structural principles about neural network that have general application.

描述（由申请人提供）：大脑包含大量神经元，其连接是由轴突和树突过程形成的，是控制行为的电路的结构基础。电路的分析非常重要。只有知道处理这些功能的大脑隔室中的电路，才能理解所有精细运动控制，记忆形成和认知的行为。同样，对精神疾病机制及其药理治疗的洞察力需要详细了解脑电路。例如，最近的发现表明，自闭症或精神分裂症等疾病可以从前额叶皮质的微电路中的异常来理解。我们建议在这笔赠款中开发和利用生物信息学工具，使我们能够解决果蝇大脑中的电路。果蝇中央大脑是由刻板印象的大约100个配对谱系形成的，每个谱系均来自一个神经细胞。一个谱系形式过程的神经元在大脑的离散室内传播。因此，谱系代表了脑宏观交流的最合适的结构/发育单元。重建所有谱系的投影意味着在神经元种群水平（“宏观交流”）上生成了精确的果蝇脑电路图。我们建议以标准化的电子格式呈现此地图，该地图可用于神经生物学社区。此外，我们将在单个突触水平（“微路”）的水平上重建电路，该电路需要电子显微镜（EM）。我们已经开发了大型EM图像数据集的自动记录，注册和导航所需的软件。我们将进一步改进并使用这些工具来生成数字EM数据集，该数据集首次涵盖具有大量结构复杂神经元的动物的整个大脑。我们的软件使我们能够有效地重建大脑不同部分遇到的神经网络。我们预计我们将能够学习有关具有一般应用的神经网络的结构原则。