ゼブラフィッシュ手綱核-縫線核経路は逃避行動学習を制御する
The Habenula-Raphe pathway Regulates Active Avoidance Learning in Zebrafish

○天羽 龍之介 / Ryunosuke Amo:1　揚妻 正和 / Masakazu Agetsuma:1,2　木下 雅恵 / Masae Kinoshita:1　 白木 利幸 / Toshiyuki Shiraki:1　青木 田鶴 / Tazu Aoki:1　山崎 昌子 / Masako Yamazaki:1　東島 眞一 / Shin-ichi Higashijima:3　 松田 勝 / Masaru Matsuda:4　Maximilia Suster:5　川上 浩一 / Koichi Kawakami:5　大島 登志男 / Toshio Ohshima:6　 相澤 秀紀 / Hidenori Aizawa:1,7　岡本 仁 / Hitoshi Okamoto:1　

1:理研BSI発生遺伝子制御 / RIKEN BSI, Saitama　
2:コロンビア大 / Dept Biological Sciences, Columbia Univ, New York　
3:岡崎統合バイオサイエンスセンター生理研 / NIPS, Okazaki Institute for Integrative Bioscience, Aichi　
4:宇都宮大学バイオサイエンス教育研究センター / Center for Bioscience Research and Education, Utsunomiya Univ, Tochigi　
5:国立遺伝研個体遺伝初期発生 / Division of Molecular and Developmental Biology, NIG, Shizuoka　
6:早稲田大院先進理工生医 / Dept Life Science and Medical Bioscience, Waseda Univ, Tokyo　
7:東京医科歯科大分子神経科学研究室 / Dept Molecular Neurosciences, Tokyo Medical and Dental Univ, Tokyo　

Appropriate choice of voluntary behavior such as avoiding predictable danger is critical for animals to survive. Monoaminergic modulation of neural circuits including the cortico-basal ganglia circuit is one of the key mechanisms regulating this behavior. Recent studies have suggested that the lateral habenula conveys negative emotional information. Interestingly, anatomical and electrophysiological studies showed that the lateral habenula regulates the activity of midbrain dopaminergic neurons and serotonergic neurons in the raphe. Although the lateral habenula is a major afferent of the raphe, function of the habenula-raphe pathway is poorly understood. We previously identified the homolog of the mammalian lateral habenula in zebrafish, the ventral habenula. Notably, the ventral habenula projects exclusively to the raphe but not to the dopaminergic nuclei in zebrafish. In this study, we have successfully established a transgenic fish line expressing tetanus toxin to inhibit neural transmission in the ventral habenula-raphe pathway. We found that Inhibition of the ventral habenula impaired active avoidance learning, a type of operant conditioning, while learning of classical fear conditioning was unaffected. Furthermore, ventral habenula neurons were phasically excited by an aversive stimulus and optogenetic stimulation of ventral habenula axons increased the firing of serotonergic neurons in the raphe. Taken together, our study suggests that the evolutionarily conserved lateral habenula-raphe pathway conveys negative emotional information to modify behavior to avoid danger through the regulation of serotonergic neurons.