The purpose of this project will be to develop the zebrafish (Danio rerio) into a useful model system for understanding the cellular and molecular mechanisms underlying learning and memory. Towards this end, behavioral investigations of several simple forms of learning in this vertebrate organism will be examined. The behavioral experiments will focus on experience-dependent modulation of the fish's startle reflex. The research will focus on simple forms of learning, including habituation and sensitization of the startle reflex in larval zebrafish The Principal Investigator will attempt to demonstrate more long-lasting forms of learning in zebrafish larvae, particularly intermediate- and long-term habituation and sensitization. In addition, the project will investigate whether the startle reflex can undergo associative learning. He will attempt to show a type of learned fear in the fish: the fear-potentiated startle reflex. Given that robust forms of learning can be developed for use in zebrafish larvae, pharmacological techniques will be used to begin to understand the neural and molecular processes that underlie associative learning in the fish. For example, training will be performed in inhibitors of protein or RNA synthesis in order to determine whether the various forms of memory depend on translation or gene transcription. Furthermore, specific inhibitors of the activity of various protein kinases and protein phosphatases will be used to test for roles for these kinases/phosphatases in learning in zebrafish. The proposed experiments will contribute significantly to an understanding of how the brain mediates learning and memory, as well cognition. Such knowledge should be highly useful for improving educational methods in the United States and will offer undergraduate students unique training opportunities using state-of-the-art methodologies.
