Gene c analysis of anxiety-related behavior in zebrafish

Yuri Kotani1,2, Koichi Kawakami1,3

1. Division of Molecular and Developmental Biology, Na onal Ins tute of Gene cs, Mishima, Shizuoka, Japan
2. Japan Society for the Promo on of Science (JSPS), Tokyo, Japan
3. Department of Gene cs, Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan

Amygdala, a center of decision-making, memory and emo onal responses, is one of key components of the anxiety circuit. We are interested in dissec ng precise neural circuits and understanding the molecular mechanism of anxiety using zebrafish. From neuroanatomical and hodological studies in zebrafish, it has been proposed that the medial zone of dorsal telencephalon (Dm) is a homolog of the mammalian amygdala. The emx3 gene, encoding a homeodomain transcrip onal factor, is expressed in neurons in Dm at the adult stage and in the forebrain at the larval stage. In order to test whether, emx3 is essen al for func ons of the Dm neurons, we generated emx3 homozygous mutants using the CRISPR/Cas9 method and analyzed them for an anxiety-related behavior, namely novel tank assay. We found the emx3 homozygous mutants showed severer phenotypes in the novelty-evoked anxiety behavior, compared to sibling controls. This indicates that the emx3 gene may be involved in reduc on of anxiety. We think that these func ons may possibly be correlated with anxiety disorders that show an excessive fear response and/or increased anxiety. We are inves ga ng how the emx3 gene knockout a ects the func on and forma on of the emx3-expressing neurons in Dm.