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A microfluidic device to study electrotaxis and dopaminergic system of zebrafish larvae

机译:用于研究斑马鱼幼虫的电出租车和多巴胺能系统的微流控装置

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摘要

The zebrafish is a lower vertebrate model organism offering multiple applications for both fundamental and biomedical research into the nervous system from genes to behaviour. Investigation of zebrafish larvae's movement in response to various stimuli, which involves the dopaminergic system, is of interest in the field of sensory-motor integration. Nevertheless, the conventional methods of movement screening in Petri dishes and multi-well plates are mostly qualitative, uncontrollable, and inaccurate in terms of stimulus delivery and response analysis. We recently presented a microfluidic device built as a versatile platform for fluid flow stimulation and high speed time-lapse imaging of rheotaxis behaviour of zebrafish larvae. Here, we describe for the first time that this microfluidic device can also be used to test zebrafish larvae's sense of the electric field and electrotaxis in a systemic manner. We further show that electrotaxis is correlated with the dopamine signalling pathway in a time of day dependent manner and by selectively involving the D2-like dopamine receptors. The primary outcomes of this research opens avenues to study the molecular and physiological basis of electrotaxis, the effects of known agonist and antagonist compounds on the dopaminergic system, and the screen of novel pharmacological tools in the context of neurodegenerative disorders. We propose that this microfluidic device has broad application potential, including the investigation of complex stimuli, biological pathways, behaviors, and brain disorders.
机译:斑马鱼是一种低等脊椎动物模型生物,可为从基因到行为的神经系统基础和生物医学研究提供多种应用。涉及多巴胺能系统的斑马鱼幼虫响应各种刺激的运动研究是感觉运动整合领域的研究热点。然而,在刺激培养和反应分析方面,在培养皿和多孔板中进行运动筛查的常规方法大多是定性的,不可控制的和不准确的。我们最近提出了一种微流体装置,该装置被构建为多功能平台,用于流体流动刺激和斑马鱼幼虫的流变行为的高速延时成像。在这里,我们首次描述了这种微流体装置还可以用于系统地测试斑马鱼幼虫对电场和电的感觉。我们进一步表明,电出租车与多巴胺信号通路在一天中依赖时间的方式,并通过选择性地涉及D2样多巴胺受体相关。这项研究的主要成果为研究电生理学的分子和生理基础,已知的激动剂和拮抗剂化合物对多巴胺能系统的作用以及在神经退行性疾病中筛选新型药理学手段开辟了道路。我们建议这种微流体装置具有广泛的应用潜力,包括复杂刺激,生物途径,行为和脑部疾病的调查。

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