Deficiency of Serotonin in Raphe Neurons and Altered Behavioral Responses in Tryptophan Hydroxylase 2-Knockout Medaka (Oryzias latipes)

作者：Ansai Satoshi; Hosokawa Hiroshi; Maegawa Shingo; Naruse Kiyoshi; Washio Youhei; Sato Kenji; Kinoshita Masato^*

来源：Zebrafish, 2017, 14(6): 495-507.

DOI：10.1089/zeb.2017.1452

• medaka
• serotonin
• knockout
• tryptophan hydroxylase
• behavior

Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2(13/13)) lacked the ability to synthesize 5-HT in the raphe neurons. To investigate the effects of 5-HT deficiency in adult behaviors, the mutant fish were subjected to five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and two-fish social interaction). The homozygous mutation caused a longer duration of freezing response in all examined paradigms and reduced the number of entries to the top area in the diving test. In addition, the mutants exhibited a decreased number of mirror-biting in the males and an increased contact time in direct social interaction between the females. These results indicate that this tph2-knockout medaka serves as a good model to analyze the effects of 5-HT deficiency in the raphe neurons.

• 出版日期2017-12