The Body Size of Stimulus Conspeciﬁcs Affects Social Preference in a Binary Choice Task in Wild-Type, But Not in dyrk1aa Mutant, Zebraﬁsh Morteza Aslanzadeh, 1, * Krishan Ariyasiri, 1, * Oc-Hee Kim, 1 Tae-Ik Choi, 1 Jae-Hoon Lim, 1 Hyung-Goo Kim, 2 Robert Gerlai, 3 and Cheol-Hee Kim 1 Abstract The zebraﬁsh has become an appropriate animal model in the analysis of numerous human brain disorders. A variety of neuropsychiatric conditions and neurodevelopmental disorders are comorbid with abnormal social behavior. Given the translational relevance of zebraﬁsh, multidisciplinary studies employing behavioral, neu- robiological, and molecular methods with this species may provide insights into human central nervous system (CNS) disorders. Many of these studies impinge upon our ability to properly induce and quantify the behavior of zebraﬁsh, a relatively understudied aspect of this species. In this study, we investigate how the body size of conspeciﬁcs relative to that of the test subject inﬂuences social (shoaling) responses in zebraﬁsh. We found a robust preference by wild-type (WT) test zebraﬁsh toward big conspeciﬁcs, but not toward smaller conspeciﬁcs. Additionally, we tested an autism-relevant zebraﬁsh knockout (KO) model. The dyrk1aa KO zebraﬁsh showed impaired social preference compared with WT in the social behavior test. Our results conﬁrm the effect of relative body size on social preference and that the social preference task developed for zebraﬁsh may uncover the function of genes and biological mechanisms potentially associated with human CNS disorders. Keywords: autism spectrum disorders, social behavior, shoaling, social preference task, Danio rerio Introduction A nalysis of animal behavior is often regarded as a crucial method for establishment of appropriate animal models of human neuropsychiatric disorders as well as for in- vestigation of the mechanisms of such disorders. The zebraﬁsh has been a popular animal model of developmental biology, but more recently, it has also started to be employed by behavioral geneticists due to the sophisticated genetic tools developed for this species and due to the complex behavioral repertoire it possesses. 1,2 For example, adult zebraﬁsh exhibit a variety of behaviors that can be easily induced and quantiﬁed relevant to the analysis and modeling of autism spectrum disorder (ASD). 3 In addition, zebraﬁsh are also utilized in psychopharmacology, for example, for screening neuroactive drugs for efﬁcacy in central nervous system (CNS) disease models. 4 Numerous features of shoal mates, or conspeciﬁcs, have been suggested to inﬂuence shoaling (social preference)-related re- sponses. For example, the color, shape, and speed of move- ment, 5 as well as the size of stimulus zebraﬁsh, 6 have been found to inﬂuence how test ﬁsh respond to these stimuli. Our study focused on one of these factors, the relative size of conspeciﬁcs. One could hypothesize several scenarios in which the rel- ative size of the ﬁsh approaching a shoal of conspeciﬁcs may inﬂuence whether the ﬁsh prefers joining the shoal. For in- stance, protection from predators may be enhanced when the approaching ﬁsh joins a group of conspeciﬁcs whose body size is larger than its own. Another possibility is that joining a group made up of smaller individuals is adaptive for the new- comer because its larger size guarantees higher dominance status and, with it, better access to mates and food. Most stud- ies observed that test ﬁsh prefer same-sized shoal mates, likely because of the phenomenon known as the oddity effect, that is, the effect of standing out in the crowd resulting in increased probability of being spotted and eaten by the predator. 5,7 Which of these strategies (preference for larger, smaller, or same-sized shoal mates) is/are typical of zebraﬁsh have only been studied in one report, which found that the strongest 1 Department of Biology, Chungnam National University, Daejeon, South Korea. 2 Neurological Disorder Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar. 3 Department of Psychology, University of Toronto Mississauga, Mississauga, Canada. *These authors contributed equally to this work. ZEBRAFISH Volume 16, Number 3, 2019 ª Mary Ann Liebert, Inc. DOI: 10.1089/zeb.2018.1717 262 Downloaded by 54.163.42.124 from www.liebertpub.com at 06/27/20. For personal use only.