Behavioral responses of zebrafish larvae to environmental cues are important functional readouts that should be evoked on-demand and studied phenotypically in behavioral, genetical and developmental investigations. Very recently, it was shown that zebrafish larvae execute a voluntary and oriented movement toward the positive electrode of an electric field along a microchannel. Phenotypic characterization of this response was not feasible due to larva's rapid movement along the channel. To overcome this challenge, a microfluidic device was introduced to partially immobilize the larva's head while leaving its mid-body and tail unrestrained in a chamber to image motor behaviors in response to electric stimulation, hence achieving quantitative phenotyping of the electrically evoked movement in zebrafish larvae. The effect of electric current on the tail-beat frequency and response duration of 5-7 days postfertilization zebrafish larvae was studied. Investigations were also performed on zebrafish exposed to neurotoxin 6-hydroxydopamine and larvae carrying a pannexin1a (panx1a) gene knockout, as a proof of principle applications to demonstrate on-demand movement behavior screening in chemical and mutant assays. We demonstrated for the first time that 6-hydroxydopamine leads to electric response impairment, levodopa treatment rescues the response and panx1a is involved in the electrically evoked movement of zebrafish larvae. We envision that our technique is broadly applicable as a screening tool to quantitatively examine zebrafish larvae's movements in response to physical and chemical stimulations in investigations of Parkinson's and other neurodegenerative diseases, and as a tool to combine recent advances in genome engineering of model organisms to uncover the biology of electric response.

中文翻译：

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使用对电刺激的按需响应对斑马鱼幼虫进行表型化学和突变筛选。

斑马鱼幼虫对环​​境线索的行为反应是重要的功能性表述，应在行为，遗传和发育研究中按需诱发和表型研究。最近，研究表明，斑马鱼幼虫沿着微通道向电场的正极执行自愿的定向运动。由于幼虫沿通道的快速运动，这种反应的表型表征是不可行的。为了克服这一挑战，引入了一种微流控设备来部分固定幼虫的头部，同时使其中体和尾巴不受约束地留在室内，以对响应电刺激的运动行为进行成像，从而实现斑马鱼幼虫中电诱发运动的定量表型分析。 。研究了电流对受精后斑马鱼幼虫5-7天的尾部拍频和反应持续时间的影响。还对斑马鱼暴露于神经毒素6-羟基多巴胺和携带pannexin1a（panx1a）基因敲除的幼虫进行了研究，以证明其在化学和突变分析中按需运动行为筛选的原理性应用证明。我们首次证明了6-羟基多巴胺会导致电反应障碍，左旋多巴治疗可以挽救反应，panx1a参与了斑马鱼幼虫的电诱发运动。我们设想，我们的技术将广泛用作筛查工具，以定量检查斑马鱼幼虫对物理和化学刺激的反应，以研究帕金森氏症。