Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.
Cell Rep Methods. 2023 Jan 5;3(1):100381. doi: 10.1016/j.crmeth.2022.100381. eCollection 2023 Jan 23.
It has been a major challenge to systematically evaluate and compare how pharmacological perturbations influence social behavioral outcomes. Although some pharmacological agents are known to alter social behavior, precise description and quantification of such effects have proven difficult. We developed a scalable social behavioral assay for zebrafish named ZeChat based on unsupervised deep learning to characterize sociality at high resolution. High-dimensional and dynamic social behavioral phenotypes are automatically classified using this method. By screening a neuroactive compound library, we found that different classes of chemicals evoke distinct patterns of social behavioral fingerprints. By examining these patterns, we discovered that dopamine D3 agonists possess a social stimulative effect on zebrafish. The D3 agonists pramipexole, piribedil, and 7-hydroxy-DPAT-HBr rescued social deficits in a valproic-acid-induced zebrafish autism model. The ZeChat platform provides a promising approach for dissecting the pharmacology of social behavior and discovering novel social-modulatory compounds.
系统评估和比较药理学干扰如何影响社会行为结果一直是一个重大挑战。虽然一些药理学药物已知会改变社会行为，但精确描述和量化这些影响一直很困难。我们开发了一种名为 ZeChat 的可扩展的斑马鱼社交行为检测方法，该方法基于无监督深度学习，可高分辨率地描述社交性。使用这种方法可以自动对高维动态社交行为表型进行分类。通过筛选神经活性化合物文库，我们发现不同类别的化学物质会引发不同模式的社交行为指纹。通过研究这些模式，我们发现多巴胺 D3 激动剂对斑马鱼具有社交刺激作用。多巴胺 D3 激动剂普拉克索、吡贝地尔和 7-羟基-DPAT-HBr 可挽救丙戊酸诱导的斑马鱼自闭症模型中的社交缺陷。ZeChat 平台为剖析社交行为的药理学和发现新型社交调节化合物提供了一种很有前途的方法。
