Action sequencing in the spontaneous swimming behavior of zebrafish larvae - implications for drug development.

All motile organisms need to organize their motor output to obtain functional goals. In vertebrates, natural behaviors are generally composed of a relatively large set of motor components which in turn are combined into a rich repertoire of complex actions. It is therefore an experimental challenge to investigate the organizational principles of natural behaviors. Using the relatively simple locomotion pattern of 10 days old zebrafish larvae we have here characterized the basic organizational principles governing the swimming behavior. Our results show that transitions between different behavioral states can be described by a model combining a stochastic component with a control signal. By dividing swimming bouts into a limited number of categories, we show that similar types of swimming behavior as well as stand-stills between bouts were temporally clustered, indicating a basic level of action sequencing. Finally, we show that pharmacological manipulations known to induce alterations in the organization of motor behavior in mammals, mainly through basal ganglia interactions, have related effects in zebrafish larvae. This latter finding may be of specific relevance to the field of drug development given the growing importance of zebrafish larvae in phenotypic screening for novel drug candidates acting on central nervous system targets.