Behavioral Neuroscience of Zebrafish

Abstract

Models are used to represent complex problems in simplified forms—physics, chemistry, and biology all make good use of models. The most familiar are the mathematical sorts that form the basis of natural science theory. In the life sciences, the concept of modeling can extend further to include experimental procedures and nonhuman subjects. For example, a neuroscientist might employ a rat running in a radial-arm maze to study working memory processes, or a mouse in an open-field test to study anxiety. The value of a model is primarily a function of its fidelity: in the case of a theoretical model, fidelity is measured in terms of predicted findings; in the case of biological models, the issue is couched in terms of validity. It is this second kind of model that concerns us in this chapter on neuroscience methods, where the challenge of model species is particularly acute because behavioral and brain processes are both extraordinarily complex, and the problem is to find species that display both interesting behavior and easily accessible neural processes.Rats and mice, unquestionably the most successful models in neuroscience, have been extremely effective in helping determine which mammalian brain regions and neurotransmitter systems involved in cognition, learning, and other varieties of behavioral function. But the invertebrate Aplysia, a marine mollusk, has also served as a molecular model of memory processes [1]. Such seemingly unrelated model species are useful to the extent that they balance external validity, simplicity, and cost. Most recently these considerations have led researchers in behavioral neuroscience to use fish, a sort of middle ground between rodents and mollusks. In this chapter we review progress in the behavioral neuroscience of the diminutive zebrafish (Danio rerio), a species that has already firmly established itself as a model of vertebrate development, and now opens new doors for the investigation of brain mechanisms.Zebrafish are sometimes identified as an alternative model (relative to classic rodent models), but the term complementary model might be more appropriate since it addresses the use of fish in addition to classic mammalian models. Some questions, such as about the role of frontal cortical and hippocampal structures in learning and memory, cannot be studied with fish since these are not evident (but see [2]). But other attributes of fish make them valuable models in behavioral neuroscience research. Developmental processes can be continuously visualized in species that have a clear chorion (egg sack). Reporter systems can highlight specific neural systems so that their proliferation, differentiation, migration, and projections can be easily discerned. Reversible genetic suppression through the morpholino technique can determine the importance of specific molecular mechanisms for neurodevelopment. Numerous mutants available also help with the evaluation of molecular mechanisms throughout life. Finally, fish are easily bred in great numbers and develop rapidly, reducing the cost of experimentation and significantly increasing research throughput—potentially, more experiments can be run in less time to answer any number of questions.The merit of fish models is now a matter of record. Zebrafish, in particular, have been well used in genetics, neuroscience, pharmacology, and toxicology (e.g., see [3–7]). The next and ongoing step is to extend the zebrafish model to pursue questions of behavioral neuroscience, an undertaking that requires valid, reliable, and efficient methods of behavioral assessment.