4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.
4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.
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DOI：
10.1038/s41598-017-06646-6
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发表时间：
2017-07-26
影响因子：
4.6
通讯作者：
Tyler CR
中科院分区：
文献类型：
--
作者：
Winter MJ;Windell D;Metz J;Matthews P;Pinion J;Brown JT;Hetheridge MJ;Ball JS;Owen SF;Redfern WS;Moger J;Randall AD;Tyler CR
功能性神经成像，使用遗传编码的Ca 2+传感器在幼斑马鱼，提供了一个强大的组合高时空分辨率和更高的脊椎动物相关性定量神经药理学分析。在这里，我们使用具有GCaMP 6s的泛神经元表达的斑马鱼幼虫，结合光片显微镜和一种新的图像处理管道，用于多个大脑区域中化学惊厥作用的4D分析。在未经处理的幼虫，区域与自主功能，感觉处理和应激反应，一贯表现出自发活动升高。针对不同惊厥机制的药物（4-氨基吡啶，戊四唑，毛果芸香碱和士的宁）的应用导致不同的时空模式的活动。这些活动模式与已知的各自分子靶点的分布显示出一些有趣的相似之处，但关键的是也揭示了系统范围内的神经回路对刺激或抑制的反应。神经活动的药物浓度-反应曲线在解剖学定义的斑马鱼脑区的数量，并在体内幼虫电生理学，也进行了4dpf幼虫，提供了额外的措施的神经活动。我们对整个斑马鱼大脑中网络范围的化学惊厥药物活性的定量说明了这种方法在神经药理学分析中的作用，其应用范围从加速药物安全性和有效性的研究，到在人类神经系统疾病的斑马鱼模型中识别药理学改变的网络。
Functional neuroimaging, using genetically-encoded Ca2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.
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影响因子：
2.9
作者：
Hirata, Hiromi;Takahashi, Megumi;Ogino, Kazutoyo
通讯作者：
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影响因子：
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Lacoste, Alix M. B.;Schoppik, David;Robson, Drew N.;Haesemeyer, Martin;Portugues, Ruben;Li, Jennifer M.;Randlett, Owen;Wee, Caroline L.;Engert, Florian;Schier, Alexander F.
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作者：
MALOSIO, ML;MARQUEZEPOUEY, B;BETZ, H
通讯作者：
BETZ, H