Adult Zebrafish Neuroscience Behavioral Models (Dissertation Research)

Zebrafish (Danio rerio) are offering novel perspectives to investigate the nervous system as a genetically and molecularly tractable in-vivo model of complex vertebrate behavior. The balance of low cost, experimental agility and phenotypic complexity, unique to zebrafish, empowers researchers to study biochemical regulators of development, behavior and disease pathogenesis in ways previously unapproachable. Larval zebrafish assays have demonstrated the value of integrating behavioral tests with high-throughput quantification techniques by successfully identifying psychotropic compounds and predicting neurological targets based on large-scale analysis of variation in behavioral responses. Pre-clinical drug discovery and behavioral genetics stands to benefit greatly from high-throughput screening assays using adult zebrafish. However, a characterization and quantification technique of adult zebrafish behavioral phenotypes requires standardization before such assays can be realized. This dissertation provides characterization of adult zebrafish behavior following ethological and pharmacological experimental treatments in affective and social domains. Behavior is quantified manually, as well as using automated video-tracking software, and correlated with a physiological biomarker (i.e. whole-body cortisol) to verify phenotypic states. In addition, a novel method of neurophenotyping using three-dimensional swim trajectory reconstructions is presented to enable rapid identification of treatment specific movement patterns. Collectively, this research provides a foundation for future studies pursing high-throughput behavioral phenotyping in adult zebrafish, and their application to modeling complex human disorders.