The analysis of the function of cerebellar neural circuitry in fear conditioning

• Project/Area Number: 18K06333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: Nagoya University
• Principal Investigator: Shimizu Takashi 名古屋大学, 理学研究科, 准教授 (50324760)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 小脳 / 恐怖条件付 / 神経回路 / ゼブラフィッシュ / 社会性行動 / 回避学習 / 神経発生 / 顆粒細胞 / 恐怖応答 / 条件付け / 恐怖 / 学習

Outline of Final Research Achievements

In the present study, we attempted to elucidate the role of cerebellar neural circuits in fear conditioning using zebrafish as a model animal. When adult zebrafish are repeatedly exposed to fearful stimuli such as electric shocks (unconditioned stimuli) and harmless stimuli such as lights (conditioned stimuli), they learn the relationship between the two stimuli and show escape behavior when only conditioned stimuli are given. In fish whose cerebellar neural circuits were inhibited, this learning was significantly reduced, indicating that the cerebellum plays an important role in fear conditioning. In addition, social behaviors of the fish with inhibited cerebellar neural circuits were observed to be impaired. These results suggest that the cerebellum is involved not only in motor learning but also in fear conditioning and social behavior.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ゼブラフィッシュを用いて小脳神経回路が恐怖条件付けや回避学習に関与していることを明らかとした。自由遊泳下では恐怖応答に関与する連合学習に小脳神経回路が重要な役割を果たしていると考えられた。さらにセブらフィッシュにおいても社会性行動に小脳神経回路が関与しており、社会性行動の神経基盤は魚類から哺乳類に到るまで保存されている可能性が示唆された。また、これらの結果は自閉症などの神経疾患の原因解明に有効であると考えられる。

Research Products

• [Journal Article] Involvement of cerebellar neural circuits in active avoidance conditioning in zebrafish. (2021)
  • Author(s): Koyama W, Hosomi R, Matsuda K, Kawakami K, Hibi M, Shimizu T.
  • Journal Title: eNeuro Volume: in press
  • Peer Reviewed
• [Journal Article] ゼブラフィッシュ小脳神経回路の発生と機能 (2021)
  • Author(s): 清水貴史、日比正彦
  • Journal Title: 生体の科学 Volume: 72 Pages: 3-8
• [Journal Article] Gsx2 is required for specification of neurons in the inferior olivary nuclei from Ptf1a-expressing neural progenitors in zebrafish. (2020)
  • Author(s): Itoh T, Takeuchi M, Sakgami M, Asakawa K, Sumiyama K, Kawakami K, Shimizu T, Hibi M.
  • Journal Title: Development Volume: 147
  • DOI: 10.1242/dev.190603
  • Peer Reviewed / Open Access
• [Journal Article] Role of Reelin in cell positioning in the cerebellum and the cerebellum-like structure in zebrafish. (2019)
  • Author(s): Nimura T, Itoh T, Hagio H, Hayashi T, Di Donato V, Takeuchi M, Itoh T, Inoguchi F, Sato Y, Yamamoto N, Katsuyama Y, Del Bene F, Shimizu T, Hibi M.
  • Journal Title: Dev Biol. Volume: 455 Issue: 2 Pages: 393-408
  • DOI: 10.1016/j.ydbio.2019.07.010
  • NAID: 120006808762
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tracing of Afferent Connections in the Zebrafish Cerebellum Using Recombinant Rabies Virus (2019)
  • Author(s): Dohaku Ryuji、Yamaguchi Masahiro、Yamamoto Naoyuki、Shimizu Takashi、Osakada Fumitaka、Hibi Masahiko
  • Journal Title: Frontiers in Neural Circuits Volume: 13 Pages: 1-15
  • DOI: 10.3389/fncir.2019.00030
  • Peer Reviewed / Open Access
• [Presentation] Investigations of effectivity of novel optogenetic tools controlling intracellular second messengers in neurons and the heart muscle (2020)
  • Author(s): Hagio, H., Koyama, W., Hosaka, S., Narantsatsral, J., Matsuda, K., Shimizu, T., Koyanagi, M., Hosohima, S., Tsunoda, S.P., Terakita, A, Kandori, H, Hibi, M.r
  • Organizer: 26th Japanese Medaka and Zebrafish Meeting
• [Presentation] Molecular mechanisms that control differentiation of Purkinje cells in zebrafish (2020)
  • Author(s): Itoh, T., Yura, S., Nakanishi, A., Uehara, M., Shimizu, T., Hibi, M.
  • Organizer: 26th Japanese Medaka and Zebrafish Meeting
• [Presentation] Role of cerebellar neural circuitry in active avoidance conditioning in zebrafish (2020)
  • Author(s): Koyama, W., Hosomi, R., Matsuda, K., Kawakami, K., Hibi, M., Shimizu, T.
  • Organizer: 26th Japanese Medaka and Zebrafish Meeting
• [Presentation] 細胞内二次メッセンジャーの光操作開発 (2020)
  • Author(s): 清水 貴史、萩尾 華子、Janchiv Narantsatsral、松田 光司、小柳 光正、寺北 明久、細島 頌子、角田 聡、神取 秀樹、日比 正彦
  • Organizer: 第43回日本神経科学大会
• [Presentation] 能動的回避学習におけるゼブラフィッシュの小脳の役割 (2020)
  • Author(s): 小山 航, 細見 椋, 松田 光司, 川上 浩一, 日比 正彦, 清水 貴史
  • Organizer: 第43回日本神経科学大会
• [Presentation] Cfdp1 regulates cell cycle and differentiation of granule cells in the zebrafish cerebellum. (2019)
  • Author(s): Shimizu T, Inoue S, Xiaodoing Sun, Hibi M.
  • Organizer: 第52回日本発生生物学会大会
• [Presentation] Roles of transcription regulators Foxp1b/Foxp4 and Skor1b/Skor2 in differentiation of Purkinje cells in zebrafish cerebellum. (2019)
  • Author(s): Yura S, Itoh T, Shimizu T, Hibi M.
  • Organizer: 第52回日本発生生物学会大会
• [Presentation] Molecular mechanisms for differentiation of the inferior olivary nucleus neurons in zebrafish. (2019)
  • Author(s): Itoh T, Takeuchi M, Sakagami M, Shimizu T, Hibi M.
  • Organizer: 第52回日本発生生物学会大会
• [Presentation] Generation of novel optogenetic tools controlling intracellular second messengers in neurons. (2019)
  • Author(s): Hagio H, Matsuda K, Shimizu T, Nagata T, Koyanagi M, Terakita A, Hibi M.
  • Organizer: 第25回小型魚類研究会
• [Presentation] Optogenetic manipulation of zebrafish neural circuits toward understanding higher order function of the cerebellum. (2018)
  • Author(s): Shimizu T, Matsuda K, Hibi M.
  • Organizer: 第56回日本生物物理学会年会
  • Invited
• [Presentation] Transcriptional regulators controlling formation of the cerebellar neural circuits. (2018)
  • Author(s): Hibi M, Itoh T, Yura S, Matsuda K, Shimizu T.
  • Organizer: 5th Imaging Structure and Function in the Zebrafish Brain Conference
  • Int'l Joint Research
• [Presentation] Involvement of axonal transport of Reelin in the layer and the neural circuit formation of the cerebellum and the optic tectum. (2018)
  • Author(s): Hibi M, Nimura T, Itoh T, Hayashi T, Takeuchi M, Di Donata V, Del Bene F, Shimizu T.
  • Organizer: 13th International Zebrafish Conference
  • Int'l Joint Research
• [Presentation] The cerebellar neural circuits differentially regulate freezing and active avoidance responses in the classical fear conditioning. (2018)
  • Author(s): Matsuda K, Yoshida M, Hosomi R, Tanabe H, Kawakami K, Hibi M, Shimizu T.
  • Organizer: 13th International Zebrafish Conference
  • Int'l Joint Research
• [Presentation] Roles of cerebellar neural circuits in active avoidance conditioning and classical fear conditioning in zebrafish. (2018)
  • Author(s): Matsuda K, Yoshida M, Hosomi R, Tanabe H, Kawakami K, Hibi M, Shimizu T
  • Organizer: 第24回小型魚類研究会
• [Book] ゼブラフィッシュ実験ガイド 第１７章実験に必要な手続き (2020)
  • Author(s): 日比正彦、清水貴史、橋本寿史、井原邦夫
  • Total Pages: 8
  • Publisher: 朝倉書店
  • ISBN: 9784254171730
• [Remarks] Gsx2はPtf1a陽性神経前駆細胞から下オリーブ核ニューロンへの運命決定に必要である
  • URL: https://www.bio.nagoya-u.ac.jp/paper/2020-36/08.html
• [Remarks] 名古屋大学大学院理学研究科生命理学専攻動物器官機能学グループ ホームページ
  • URL: http://bbc.agr.nagoya-u.ac.jp/~junkei/new/index.html
• [Remarks]
  • URL: http://bbc.agr.nagoya-u.ac.jp/~junkei/new/index.html