Establishment of the miniature fish species Danionella translucida as a genetically and optically tractable neuroscience model

The rapid adoption of the larval zebrafish as a systems neuroscience model has been driven largely by its small size and optical transparency, which enable the use of imaging and optogenetics techniques to record and manipulate activity throughout the brain. Unfortunately, larval fish lack the sophisticated behavioral repertoire of adults and so a number of complex learning phenomena and social behaviors cannot be investigated in these animals. Here we establish the pedomorphic fish species Danionella translucida as a laboratory model that overcomes this limitation. Adult Danionella possess the size and optical transparency of late-larval zebrafish, which we exploit to image deep within the brains of a behaviorally mature animals using two-photon microscopy. The close phylogenetic relationship between Danionella and zebrafish enabled us to use existing reagents and techniques for transgenesis, and zebrafish-derived enhancer elements drove transgene expression in Danionella with the intended specificity. In a behavioral assay for socially-reinforced place preference, interactions between fish were found to be positively reinforcing, demonstrating the power of this species for studies of learning and memory as well as social behavior. The establishment of Danionella9s behavioral, molecular, and optical tractability provides a unique opportunity for researchers seeking to understand the relationship between circuits and complex behaviors at a whole-brain level.