Neuroscientists face the difficult task of describing the coordinated activities of many single neurons across the brain, and explaining how the cells' firing patterns create behavior. Achieving this goal at the immense scale of the human brain is the ultimate goal of the BRAIN Initiative. To accomplish this complex goal, it first is necessary to establish appropriate experimental and analytical techniques, as well as a better understanding of basic circuit principles, in simpler systems. The current project expands the opportunities for gaining insight by developing a new laboratory model organism. The candidate species is the fish Danionella translucida. This species is very small (~1 cm body length as an adult) and optically transparent, two characteristics that make the species exquisitely well-suited to molecular and optical techniques for recording from and manipulating large sets of neurons, and enabling researchers to use the most powerful experimental methods to study how each neuron in an adult vertebrate contributes to complex behaviors. The project will establish this potentially revolutionary model species and demonstrate proof-of-principle by mapping the neural circuits that underlie odor-mediated social alarm behavior in adult Danionella. The societal benefits of this work include unprecedented insight into the mechanisms of complex behaviors, some of which are affected in human neurological diseases. Additionally, the integration of multiple levels of analysis, from molecular biology to social behavior, render this project the basis of a particularly powerful neuroscience teaching tool, to be implemented through existing undergraduate and high school research programs that include outreach to students from minority groups.
This project draws on Danionella's close phylogenetic similarity to the zebrafish, Danio rerio, to apply existing experimental tools to a new animal model. The first aim is to establish breeding, transgenesis, and gene editing techniques that will allow propagation of these fish in the lab, introduction of fluorescent reporters and optogenetic actuators, and targeted manipulation of specific, endogenous genes. The second aim is to apply multiphoton and light-sheet imaging to adult Danionella, and evaluate the results against benchmarks established in larval zebrafish. The third aim is to develop assays for a pheromone-mediated social alarm behavior, and record pheromone-evoked activity from every neuron in the brain. These experiments collectively demonstrate the experimental power of this new model species and create tools that are essential for its adoption by the research community. The insights will be disseminated through, among others, existing and new websites supporting exchange among scientists.
