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Brain-wide circuit interrogation at the cellular level guided by online analysis of neuronal function
Nature Methods ( IF 48.0 ) Pub Date : 2018-11-30 , DOI: 10.1038/s41592-018-0221-x
Nikita Vladimirov , Chen Wang , Burkhard Höckendorf , Avinash Pujala , Masashi Tanimoto , Yu Mu , Chao-Tsung Yang , Jason D. Wittenbach , Jeremy Freeman , Stephan Preibisch , Minoru Koyama , Philipp J. Keller , Misha B. Ahrens

Whole-brain imaging allows for comprehensive functional mapping of distributed neural pathways, but neuronal perturbation experiments are usually limited to targeting predefined regions or genetically identifiable cell types. To complement whole-brain measures of activity with brain-wide manipulations for testing causal interactions, we introduce a system that uses measured activity patterns to guide optical perturbations of any subset of neurons in the same fictively behaving larval zebrafish. First, a light-sheet microscope collects whole-brain data that are rapidly analyzed by a distributed computing system to generate functional brain maps. On the basis of these maps, the experimenter can then optically ablate neurons and image activity changes across the brain. We applied this method to characterize contributions of behaviorally tuned populations to the optomotor response. We extended the system to optogenetically stimulate arbitrary subsets of neurons during whole-brain imaging. These open-source methods enable delineating the contributions of neurons to brain-wide circuit dynamics and behavior in individual animals.



中文翻译:

在神经元功能在线分析的指导下在细胞水平进行脑范围的电路询问

全脑成像可以对分布的神经通路进行全面的功能映射,但是神经元扰动实验通常仅限于针对预定区域或遗传可识别的细胞类型。为了用全脑操作来测​​试因果相互作用来补充全脑活动量度,我们引入了一个系统,该系统使用测得的活动模式来指导相同虚构行为的幼虫斑马鱼中任何神经元子集的光学扰动。首先,光片显微镜收集全脑数据,然后通过分布式计算系统对其进行快速分析,以生成功能性大脑图。根据这些图,实验者可以光学消融神经元,并改变大脑的图像活动。我们应用这种方法来表征行为调整的人口对光动力反应的贡献。我们扩展了该系统,以在全脑成像过程中以光遗传学方式刺激神经元的任意子集。这些开放源代码的方法能够描述神经元对单个动物大脑范围内电路动力学和行为的贡献。

更新日期:2018-12-10
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