High-throughput behavioral screens: the first step towards finding genes involved in vertebrate brain function using zebrafish

Abstract

The zebrafish has been in the forefront of developmental biology for three decades and has become a favorite of geneticists. Due to the accumulated genetic knowledge and tools developed for the zebrafish it is gaining popularity in other disciplines, including neuroscience. The zebrafish offers a compromise between system complexity (it is a vertebrate similar in many ways to our own species) and practical simplicity (it is small, easy to keep, and prolific). Such features make zebrafish an excellent choice for high throughput mutation and drug screening. For the identification of mutation or drug induced alteration of brain function arguably the best methods are behavioral test paradigms. This review does not present experimental examples for the identification of particular genes or drugs. Instead it describes how behavioral screening methods may enable one to find functional alterations in the vertebrate brain. Furthermore, the review is not comprehensive. The behavioral test examples presented are biased according to the personal interests of the author. They will cover research areas including learning and memory, fear and anxiety, and social behavior. Nevertheless, the general principles will apply to other functional domains and should represent a snapshot of the rapidly evolving behavioral screening field with zebrafish.

Figure 1

Performance during the Inter-Stimulus Intervals (ISI): percent of time test fish spent on the side of the experimental tank where the stimulus fish used to be shown (modified from [25]).

Figure 2

The natural alarm substance (Panel A) as well as the synthetic alarm substance, H3NO (Panel B) elicits increased number of erratic movement responses (modified from [39,40]).

Figure 3

Presentation of animated (moving) images of zebrafish (grey horizontal bar above the X-axis) induces a significant shoaling response: upon the presentation of the images, the experimental zebrafish moves closer to the presentation screen (modified from [27]).