Ariyasiri Krishan, Choi Tae-Ik, Kim Oc-Hee, Hong Ted Inpyo, Gerlai Robert, Kim Cheol-Hee
Department of Biology, Chungnam National University, Daejeon 34134, South Korea.
Department of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jan 10;88:53-65. doi: 10.1016/j.pnpbp.2018.06.009. Epub 2018 Jun 26.
Social behavior is a fundamental aspect of our own species, a feature without which our society would not function. There are numerous human brain disorders associated with abnormal social behavior, among them are the autism spectrum disorders whose causal factors include a genetic component. Environmental factors, including drugs of abuse such as alcohol, also contribute to numerous abnormalities related to social behavior. Several such disorders have been modeled using laboratory animals. Perhaps one of the newest among them is the zebrafish. However, the paucity of standardized behavioral assays specifically developed for the zebrafish have hindered progress. Here, we present a newly developed zebrafish behavioral paradigm, the three-chamber social choice task. This task, which was adapted from a murine model, assesses sociality and social novelty preference in zebrafish in three phases: habituation, phase-I to evaluate sociality, and phase-II to quantify social novelty preference. Test fish are placed in the middle chamber, while conspecifics are introduced to the flanking chambers during phase-I and II. Both male and female zebrafish displayed sociality (preference for conspecifics) during phase-I and social novelty preference (preference for unfamiliar conspecifics) during phase-II. We found the paradigm to be able to detect both environmentally (alcohol) as well as genetically (targeted knock out of sam2) induced alterations of behavioral phenotypes. Although ethanol-treated fish displayed similar levels of sociality to those of control (not alcohol exposed) male and female zebrafish, they were found to exhibit significantly impaired social novelty preference, a finding compatible with altered motivational or perhaps mnemonic processes. Moreover, we found that knock out of sam2, previously shown to lead to emotional dysregulation, also disrupted social novelty preference, while leaving sociality relatively intact. We conclude that our novel behavioral paradigm is appropriate for the modeling and quantification of social behavior deficits in zebrafish.
社会行为是人类物种的一个基本方面，没有这一特征，我们的社会就无法运转。有许多与异常社会行为相关的人类脑部疾病，其中包括自闭症谱系障碍，其病因包括遗传因素。环境因素，包括酒精等滥用药物，也会导致许多与社会行为相关的异常。已经使用实验动物对其中几种疾病进行了建模。也许其中最新的一种是斑马鱼。然而，专门为斑马鱼开发的标准化行为测定方法的匮乏阻碍了研究进展。在此，我们提出一种新开发的斑马鱼行为范式，即三室社会选择任务。该任务改编自小鼠模型，分三个阶段评估斑马鱼的社交性和对社会新奇性的偏好：适应阶段、第一阶段评估社交性以及第二阶段量化对社会新奇性的偏好。在第一阶段和第二阶段，将测试鱼放置在中间室，同时将同种鱼引入两侧的室中。雄性和雌性斑马鱼在第一阶段都表现出社交性（对同种鱼的偏好），在第二阶段表现出对社会新奇性的偏好（对不熟悉的同种鱼的偏好）。我们发现该范式能够检测出环境（酒精）以及基因（靶向敲除sam2）诱导的行为表型变化。虽然经乙醇处理的鱼与对照（未接触酒精）的雄性和雌性斑马鱼表现出相似水平的社交性，但发现它们对社会新奇性的偏好明显受损，这一发现与动机或记忆过程改变相符。此外，我们发现敲除sam2（先前已证明会导致情绪失调）也会破坏对社会新奇性的偏好，而社交性相对保持不变。我们得出结论，我们的新型行为范式适用于对斑马鱼社会行为缺陷进行建模和量化。
