A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay

Douglas W. Todd, Rohit C. Philip, Maki Niihori, Ryan A. Ringle, Kelsey R. Coyle, Sobia F. Zehri, Leanne Zabala, Jordan A. Mudery, Ross H. Francis, Jeffrey J Rodriguez, Abraham Jacob

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.

Original languageEnglish (US)
Pages (from-to)331-342
Number of pages12
JournalZebrafish
Volume14
Issue number4
DOIs
StatePublished - Aug 1 2017

Keywords

  • behavioral assay
  • drug discovery and development
  • hearing and hearing loss
  • ototoxicity
  • rheotaxis
  • zebrafish

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Developmental Biology

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  • Cite this

    Todd, D. W., Philip, R. C., Niihori, M., Ringle, R. A., Coyle, K. R., Zehri, S. F., Zabala, L., Mudery, J. A., Francis, R. H., Rodriguez, J. J., & Jacob, A. (2017). A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay. Zebrafish, 14(4), 331-342. https://doi.org/10.1089/zeb.2016.1412