Social Behavior in a Zebrafish Model of Schizophrenia

Sammanfattning: Schizophrenia is a severe psychiatric disorder with unsatisfactory treatment options and poorly under- stood etiology. Genetic models are a suitable tool for studying this disorder with its high heritability. However, currently available animal models do not cover the broad range of schizophrenia symptoms and are not disorder-specific. Ribonucleic acid binding motif protein 12 gene (RBM12), a novel, high- risk gene for schizophrenia, was recently identified. This thesis aimed to assess the social behavior of schizophrenia-like phenotype in RBM12 zebrafish mutants. The social behavior of mutated adult zebrafish was assessed during free-swimming. Trajectories of each zebrafish were obtained from recordings by the usage of idtracker.ai. Parameters selected to quantify the social behavior of the zebrafish were chosen based on common symptoms of humans with schizophrenia. Inter-fish distance was examined as an indicator of preferred personal space since humans diagnosed with schizophre- nia have an increased need for a greater personal space compared to mentally healthy individuals. Wall-hugging, increased speed and bottom-dwelling were studied as indicators of anxiety, a common comorbid symptom of schizophrenia. The RBM12 mutants exhibited a greater inter-fish distance than their wild-type siblings during three-dimensional recordings. They however, did not demonstrate an increased inter-fish distance during two-dimensional recordings. The mutated zebrafish displayed a higher average speed and greater wall-hugging, indicating anxiety. It can be concluded that RBM12 mutation produces partial symptomatology consistent with humans diagnosed with schizophrenia, providing a promising animal model. The current work provided novel insight into the neural substrates of schizophrenia and for potential drug screening for this disorder. Further research is needed to fully characterise schizophrenia-like symptoms in this RBM12 animal model.