Zebrafish model systems for developmental neurobehavioral toxicology

Abstract

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models.

Figure 1

The tap startle/habituation task (Sledge et al., 2011) in which eight zebrafish are tested simultaneously. A solenoid beneath each arena provide taps at one-minute intervals for ten trials. Initial, vigorous swimming response is followed by gradual habituation of response.

Figure 2

The novel tank diving task (Bencan et al., 2009) in which zebrafish are placed in a novel narrow tank and the vertical dimension of their swimming behavior is measured. Initially, during a five-minute session the fish dive to the bottom of the novel tank and later swim to explore other levels of the tank.

Figure 3

The three-chamber task for testing learning and memory using a spatial discrimination procedure (Levin et al., 2003) in which the zebrafish is initially placed in the center chamber and then given the opportunity to swim to either of two side chambers. If the correct choice is made the fish is permitted to swim undisturbed in the choice chamber. If an incorrect choice is made the partition between chambers is moved toward the end to restrain the fish. Sequential trials are given to index learning. Spatial or nonspatial cues can be used for the discrimination.

Figure 4

Developmental diazinon exposure in zebrafish (Levin et al., 2010) on the novel tank diving task mean±sem of time spent in bottom portion of the tank is plotted for each minute of the 5 minute session, for each exposure group.

Figure 5

Developmental diazinon exposure in zebrafish (Levin et al., 2010), on the novel tank diving task, mean±sem of distance travelled is plotted for each minute of the 5 minute session, for each exposure group.