Rapid well-plate assays for motor and social behaviors in larval zebrafish

Behavior phenotypes are a powerful means of uncovering subtle xenobiotic chemical impacts on vertebrate nervous system development. Rodents manifest complex and informative behavior phenotypes but are generally not practical models in which to screen large numbers of chemicals. Zebrafish recapitulate much of the behavioral complexity of higher vertebrates, develop externally and are amenable to assay automation. Short duration automated assays can be leveraged to screen large numbers of chemicals or comprehensive dose-response for fewer chemicals. Here we describe a series of mostly automated assays including larval photomotor response, strobe light response, blue color avoidance, shoaling and mirror stimulus-response performed on the ZebraBox (ViewPoint Behavior Technologies) instrument platform. To explore the sensitivity and uniqueness of each assay endpoint, larval cohorts from 5 to 28 days post fertilization were acutely exposed to several chemicals broadly understood to impact different neuro-activities. We highlight the throughput advantages of using the same instrument platform for multiple assays and the ability of different assays to detect unique phenotypes among different chemicals.