Neural circuits in zebrafish: form, function and plasticity

斑马鱼的神经回路：形式、功能和可塑性

基本信息

批准号：
8826324
负责人：
CONSTANCE L CEPKO
金额：
$ 173.64万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8826324
关键词：
Animals Area Behavior Behavioral Behavioral Assay Behavioral Paradigm Brain Calcium Cells Code Complement Complex Computer Simulation Data Data Set Development Electron Microscopy Engineering Fishes Functional Imaging Future Generations Goals Image Label Larva Machine Learning Maps Mathematics Measures Mental disorders Modality Modeling Mono-S Motion Motor Motor output Nature Neurodevelopmental Disorder Neurons Neurosciences Noise Output Pattern Plastics Process Reflex action Research Resolution Sensory Sensory Process Stimulus Structure Subgroup Synapses Techniques Technology Transgenic Organisms Viral Virus Virus Receptors Zebrafish base calcium indicator cell type computerized tools design experience in vivo information processing insight learned behavior light microscopy neural circuit public health relevance reconstruction relating to nervous system research study response scaffold statistics theories tool two-photon virtual virtual reality visual stimulus

项目摘要

DESCRIPTION (provided by applicant): We propose to combine whole brain 2-photon imaging of neural activity in behaving larval zebrafish with detailed anatomical and connectivity information extracted from the same animals. The final goal is to generate quantitative models of brain wide neural circuits that explain the dynamic processing of sensory information as well as the generation of motor output by these circuits. Anatomical data will be generated by two complementary technologies: 1) whole brain EM data sets will be prepared from the same fish that were used for calcium imaging. Respective data sets will be registered to each other, functionally relevant neuronal ensembles will then be identified in the EM stacks and connectivity will be analyzed in these sub-networks via sparse reconstruction. 2) EM based connectivity information will be supplemented by trans-synaptic viral tracing technology. These two technologies for identifying synaptic connections have complementary strengths and weaknesses and are thus ideally suited for combination with in-vivo 2-photon calcium imaging studies. The specific power of this approach is that all three techniques, whole brain calcium imaging, viral tracing and EM reconstruction, can be done in the same animal. Functional, anatomical and behavioral data can then be analyzed in the context of the specific stimuli and quantified behavioral output and subsequently synthesized into a theoretical framework. To that end we will start with quantitative models of simple reflex behaviors, like the optomotor and optokinetic reflex, where the transformation of sensory input to motor output is relatively straightforward and well defined. These elementary models will serve as a scaffold that can be refined and complemented by additional data from structure function studies from fish performing in more sophisticated behavioral assays that involve more complex stimuli, different modalities and plastic changes. As such the process of building such a "virtual fish" will be an iterative, open ended process that requires continuous and bidirectional exchange of information between the theoretical and experimental groups of the research team.

描述（由适用提供）：我们建议将整个脑2光子成像组合到行为幼虫斑马鱼中的神经元活性，以及从同一动物中提取的详细解剖和连通性信息。最终目标是生成大脑广泛的神经元电路的定量模型，这些模型解释了感官信息的动态处理以及这些电路的发动机输出产生。解剖学数据将由两种完整的技术生成：1）将从用于钙成像的同一条鱼中制备整个大脑EM数据集。将在功能相关的神经元集合中进行注册，然后在EM堆栈中识别与功能相关的神经元集合，并通过稀疏重建在这些子网络中分析连接性。 2）基于EM的连接信息将通过反式突触病毒追踪技术补充。这两种用于识别突触连接的技术具有完整的优势和劣势，因此非常适合与体内2-光子钙成像研究组合。这种方法的具体力量是，所有三种技术，即全脑钙成像，病毒追踪和EM重建，都可以在同一动物中完成。然后，可以在特定刺激的背景下分析功能，解剖和行为数据，并量化行为输出，然后将其合成为理论框架。为此，我们将从简单反射行为的定量模型开始，例如验光和光动力学反射，其中感觉输入对电动机输出的转换相对简单且定义良好。这些基本模型将用作脚手架，可以通过在更复杂的行为测定中进行的结构功能研究中的其他数据来完善和完成，这些数据涉及更复杂的刺激，不同的方式和塑料变化。因此，构建这样的“虚拟鱼”的过程将是一个迭代，开放的过程，需要在研究团队的理论和实验组之间进行连续和双向交换信息。