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，其连接由轴突和树突过程形成，是控制行为的电路的结构基础。电路分析非常重要。只有了解处理这些功能的脑室内的电路，才能理解精细运动控制、记忆形成和认知的所有行为。同样，深入了解精神疾病机制及其药物治疗需要详细了解大脑回路。例如，最近的研究结果表明，自闭症或精神分裂症等疾病可以通过前额皮质微电路的异常来理解。我们在这笔赠款中建议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问题。果蝇中枢大脑由大约 100 个配对谱系组成，每个谱系都源自一个神经母细胞。一种谱系的神经元形成在大脑的离散区室中传播的过程。因此，谱系代表了大脑宏观电路最合适的结构/发育单元。重建所有谱系的投影意味着在神经元群体水平上生成果蝇大脑电路的准确图（“宏电路”）。我们建议生成这张地图，以神经生物学界可以访问的标准化电子格式呈现。此外，我们将重建单个突触水平的电路（“微电路”），这需要电子显微镜（EM）。我们开发了自动记录、配准和导航大型 EM 图像数据集所需的软件。我们将进一步改进和使用这些工具来生成数字电磁数据集，该数据集首次包含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具有普遍应用的神经网络的结构原理。