The study of the hippocampal function in zebrafish.

Hideyuki Tanabe1, Pradeep Lal1,2, Akira Muto1,2, Koichi Kawakami1,2. 1) Molecular and Developmental Biology, National Institute of Genetics; 2) Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI).

Hippocampus is part of the limbic system in mammals, and plays an important role in learning and memory. To elucidate cellular and molecular basis for learning and memory, we aim to study hippocampal functions in zebrafish. First, we developed a trace two-way active avoidance conditioning system in zebrafish. In this system, green light is given as the conditioned stimulus (CS), and then an electrical shock is given as the unconditioned stimulus (US) after a temporal gap between CS and US. It has been thought that, the hippocampal function is essential to perform avoidance response in the trace conditioning paradigm. Using this assay system, we demonstrated that wild type zebrafish learn active avoidance in response to CS. Next, we have performed enhancer trap and gene trap screens, and isolated transgenic zebrafish, which had Gal4 expression in specific regions of the adult brain. We crossed them with the UAS:neurotoxin lines, inhibited neuronal activity in the specific regions and analyzed the double transgenic fish using the behavioral assay system. We found transgenic fish, which expressed Gal4 in the dorsolateral telencephalon (Dl), showed impairment of avoidance learning in the trace conditioning when crossed with UAS:neurotoxin. From this study and previous anatomical studies, tDl of zebrafish may be functional equivalent of the mammalian hippocampus.