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通过靶向γ-氨基丁酸(GABA)受体的药物制剂对斑马鱼视动反射的调节

Modulation of the zebrafish optokinetic reflex by pharmacologic agents targeting GABA receptors.

作者信息

Shao Enhua, Scheetz Seth D, Xie Wenting, Burton Edward A

机构信息

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Tsinghua University Medical School, Beijing, China.

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Neurosci Lett. 2018 Apr 3;671:33-37. doi: 10.1016/j.neulet.2018.01.055. Epub 2018 Feb 2.

DOI:10.1016/j.neulet.2018.01.055
PMID:29410359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5889744/
Abstract

Optokinetic reflex (OKR) responses provide a convenient means to evaluate visual, integrative and oculomotor function in larval zebrafish. We measured multiple aspects of the OKR response in zebrafish exposed systemically to compounds altering signaling at GABA receptors in order to derive quantitative concentration-response relationships. The GABA antagonist picrotoxin caused concentration-dependent decreases in reflex gain, saccade velocity, saccade amplitude, interocular concordance and interocular gain. Conversely, the GABA agonist gaboxadol provoked increases in reflex gain, saccade velocity, saccade amplitude and ocular range at low concentrations, and decreases in some of these parameters at higher concentrations. These data show that GABA signaling influences multiple aspects of the OKR (including gain, generation of saccades, and coordination between the two eyes) and provide proof of concept that quantitative OKR analysis can be used as a tool for chemical biology and neuropharmacology applications.

摘要

视动反射(OKR)反应为评估斑马鱼幼体的视觉、整合和眼球运动功能提供了一种便捷的方法。我们测量了全身暴露于改变GABA受体信号传导的化合物的斑马鱼OKR反应的多个方面,以得出定量的浓度-反应关系。GABA拮抗剂印防己毒素导致反射增益、扫视速度、扫视幅度、眼间一致性和眼间增益呈浓度依赖性降低。相反,GABA激动剂加波沙朵在低浓度时会引起反射增益、扫视速度、扫视幅度和眼动范围增加,而在高浓度时会使其中一些参数降低。这些数据表明,GABA信号传导影响OKR的多个方面(包括增益、扫视的产生以及双眼之间的协调),并提供了概念验证,即定量OKR分析可作为化学生物学和神经药理学应用的工具。

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An open-source method to analyze optokinetic reflex responses in larval zebrafish.开源方法分析幼斑马鱼的光偏斜反射反应。
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