A comprehensive characterizations of zebrafish rheotactic behaviors and its application to otoprotective drug screening

Aquatic animals have rheotaxis that maintains a balance in response to water flow. They sense water flow through hair cells in lateral line, thereby leading to behavior changes relevant to damages on hair cells, the primary sensory receptor cells within auditory and vestibular systems. Zebrafish are efficient animal models for high-throughput drug screening with human-like hair cells along the lateral line. Their rheotactic behaviors could be assays for hair-cell-targeted drug screening. However, knowledge and tools for rheotaxis analysis along the extent of hair-cell damage have not been fully investigated. This article aims at characterization of rheotactic behaviors identifying lateral line states via an analysis platform that simultaneously examines multiple zebrafish larvae. To this end, we developed an automated framework that incorporated animal test hardware equipment and real-time analysis software for monitoring aquatic behaviors of multiple larvae. Through this framework, a commensurable measure for one-dimensional characterization of rheotactic behaviors was consolidated so that its linear changes could be associated with the population of hair cells remaining intact. These findings satisfied requests for an automated analysis platform to conduct large-scale screening and a biomarker that discriminate the seriousness of hair cell damage to screen candidates having significant effects in otoprotective drug discovery.