ゼブラフィッシュの手綱核による恐怖行動制御

• Project Area: Systems molecular ethology to understand the operating principle of the nervous system
• Project/Area Number: 21115521
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: 岡本 仁 独立行政法人理化学研究所, 発生遺伝子制御研究チーム, シニア・チームリーダー (40183769)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 手綱核 / ゼブラフィッシュ / 恐怖行動 / トランスジェニック / 情動 / 恐怖 / 破傷風毒素 / Ga14-VP16 / 恐怖学習 / フリージング

Research Abstract

我々は、ゼブラフィッシュの背側手綱核が、更に外側と内側の亜核に分かれており、外側亜核は脚間核の背側半分に、内側亜核は脚間核の腹側半分に選択的に投射すること、左側の手綱核では外側亜核が内側亜核よりも有意に大きく、右側の手綱核ではその反対であることを発見した(Aizawa et al., Current Biology,2005 ; Devel.Cell,2007)。平成21年度には、マウスの外側手綱核が、縫線核に投射する事に基づき、ゼブラフィッシュ脳の縫線核に色素を注入し、逆行性に細胞体を染める事によって、手綱核の腹側の部分の神経細胞が染色されたことから、ゼブラフィッシュの腹側手綱核が、マウスの外側手綱核に相当する事を確認した(Amo et al., J.Neurosci.2010)。平成22年度には、腹側手綱核特異的に、神経活動の操作を行うために、手綱核特異的遺伝子のスクリーニングを行い、2つの遺伝子が、腹側手綱核特異的に発現する事を発見した。このうちのdiamine oxydase(dao)については、この遺伝子を含むBACクローンを単離し、大腸菌内での遺伝子組換えを使って、コーディング領域を、Cre recombinaseと交換した組換え体を作成し、これを用いて、トランスジェニック系統を作成した。本系統と、vglut2-loxP-dsRed-loxP-GFPを持つ別系統とをかけ合わせることによって、腹側手綱核のみで、GFPを活性化できることを明らかにした。今後、GFPの代りに破傷風毒素や、Channelrhodopsin等を、腹側特異的に発現させる事によって、腹側手綱核の神経細胞からの、神経伝達の活性を人為的に調整し、ゼブラフィッシュの行動が、どのように影響されるかを観察する予定である。

Research Products

• [Journal Article] Dual roles of notch in regulation of apically restricted mitosis and apicobasal polarity of neuroepithelial cells (2011)
  • Author(s): Ohata, S., et al.
  • Journal Title: Neuron Volume: 69(2) Pages: 215-230
  • Peer Reviewed
• [Journal Article] The habenula is crucial for experience-dependent modification of fear responses in zebrafish (2010)
  • Author(s): Agetsuma, M., et al.
  • Journal Title: Nature Neuroscience Volume: 13(11) Pages: 1354-1356
  • Peer Reviewed
• [Journal Article] Islet1 selectively promotes peripheral axon outgrowth in Rohon-Beard primary sensory neurons (2010)
  • Author(s): Tanaka, H., et al.
  • Journal Title: Developmental Dynamics Volume: 240 Pages: 9-22
  • Peer Reviewed
• [Journal Article] Characterization of neural stem cells and their progeny in the adult zebrafish optic tectum (2010)
  • Author(s): Ito, Y., Tanaka, H., Okamoto, H., Oshima, T.
  • Journal Title: Developmental Biology Volume: 342 Pages: 26-38
  • Peer Reviewed
• [Journal Article] Identification of the zebrafish ventral habenula as a homologue of the mammalian lateral habenula (2010)
  • Author(s): Amo, R.et al.
  • Journal Title: J.Neuroscience 30 Pages: 1556-1574
  • Peer Reviewed
• [Journal Article] From the olfactory bulb to higher brain centers : genetic visualization of secondary olfactory pathways in zebrafish (2009)
  • Author(s): Miyasaka N.et al.
  • Journal Title: J Neurosci. 29 Pages: 4756-4767
  • Peer Reviewed
• [Journal Article] Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hind brain (2009)
  • Author(s): Ohata S.et al.
  • Journal Title: Development 136(10) Pages: 1653-1663
  • Peer Reviewed
• [Journal Article] Roles of planar cell polarity pathway genes for neural migration and differentiation (2009)
  • Author(s): Wada H.et al.
  • Journal Title: Dev Growth Differ. 51 Pages: 233-240
  • Peer Reviewed
• [Journal Article] Roles of noncanonical Wnt/PCP pathway genes in neuronal migration and neurulation in zebrafish (2009)
  • Author(s): Wada H.et al.
  • Journal Title: Zebrafish 6 Pages: 3-8
  • Peer Reviewed
• [Presentation] Cross-species approach for the study of the neural circuits controlling emotion (2011)
  • Author(s): Hitoshi Okamoto
  • Organizer: Educational workshop for students in the medical and dental scientist training program
  • Place of Presentation: Naju Korea
  • Year and Date: 2011-01-24
• [Presentation] Imaging structure and function in the zebrafish brain (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: Imaging structure and function in the zebrafish brain
  • Place of Presentation: Lisboa Portugal
  • Year and Date: 2010-12-13
• [Presentation] Cross-species approach for the study of the neural circuits controlling emotion (2010)
  • Author(s): 岡本仁
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Habenula as the multimodal switching board for controlling behaviors (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: International symposium on brain aging and dementia : basic and translational aspects
  • Place of Presentation: Vanarasi India
  • Year and Date: 2010-11-29
• [Presentation] Zebrafish as a model system for study of fear (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: The 5th congress of Federation of Asian-Oceanian Neuroscience Societies (FAONS) and 28th annual meeting of Indian Academy of Neurosciences (IAN)
  • Place of Presentation: Lucknow India
  • Year and Date: 2010-11-27
• [Presentation] ゼブラフィッシュの研究からわかる,ヒトの脳の成り立ちと働き (2010)
  • Author(s): 岡本仁
  • Organizer: 大学グローバルCOEプログラム「機能分子医学への神経疾患・腫瘍の融合拠点」ニューロサイエンスコース
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-05
• [Presentation] Habenula as the multimodal switching board for controlling behaviors (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: Emotions : From neurochemistry and brain evolution to human behaviour
  • Place of Presentation: Genval Belgium
  • Year and Date: 2010-10-17
• [Presentation] ゼブラフィッシュ研究から見たヒトの心の成り立ち:Fish-eye's view on human mind (2010)
  • Author(s): 岡本仁
  • Organizer: 平成22年度生理学研究所情動研究会「感覚刺激・薬物による快・不快情動生成機構とその破綻」
  • Place of Presentation: 岡崎
  • Year and Date: 2010-10-01
• [Presentation] Zebrafish as a model system for study of fear (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: EU COST Action BM0804 workshop : Zebrafish as a neurophysiological and neurobehavioural model
  • Place of Presentation: London, UK
  • Year and Date: 2010-09-09
• [Presentation] Habenula as the multimodal switching board for controlling behaviors (2010)
  • Author(s): 岡本仁
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会(Neuro2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] 魚の研究から明らかになったヒトの脳の成り立ちと働き (2010)
  • Author(s): 岡本仁
  • Organizer: Neuro2010サテライトシンポジウム「脳科学におけるヒト研究と動物研究のクロスオーバー」
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-01
• [Presentation] ゼブラフィッシュの生細胞イメージング (2010)
  • Author(s): 岡本仁
  • Organizer: 第35回組織細胞化学講習会
  • Place of Presentation: 甲府
  • Year and Date: 2010-08-05
• [Presentation] ゼブラフィッシュ研究から見たヒトの心の成り立ち (2010)
  • Author(s): 岡本仁
  • Organizer: 第29回分子病理学研究会
  • Place of Presentation: つくば
  • Year and Date: 2010-07-31
• [Presentation] Habenula as the multimodal switching board for controlling bahaviors (2010)
  • Author(s): 岡本仁
  • Organizer: 脳と心のメカニズム第11回夏のワークショップ「知覚と運動」
  • Place of Presentation: 札幌
  • Year and Date: 2010-07-29
• [Presentation] Circuit formation (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: Developmental Neurobiology Course
  • Place of Presentation: Onna Village, Japan
  • Year and Date: 2010-07-19
• [Presentation] Zebrafish as a model animal to study fear (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: 43rd Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-06-23
• [Presentation] The habenula regulates experience-dependent choice of fear responses in zebrafish (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: Development of pattern in the nervous system
  • Place of Presentation: Minerve France
  • Year and Date: 2010-05-13
• [Presentation] Zebrafish as a model system for study of fear (2010)
  • Author(s): Hitoshi Okamoto
  • Organizer: 2nd International MRC symposium on Signals, Neurons and Behavior
  • Place of Presentation: Gwangju, Korea
  • Year and Date: 2010-04-07
• [Presentation] Functional analysis of the habenula in control of fear (2010)
  • Author(s): 岡本仁
  • Organizer: 11th Australian and New Zealand zebrafish workshop
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2010-02-04
• [Presentation] Functional analysis of the habenula in control of fear (2010)
  • Author(s): 岡本仁
  • Organizer: 14th IBRO-APRC associate school of neuroscience "Synaptic plasticity : From basics to clinical applications"
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2010-01-27
• [Presentation] Emotion (2010)
  • Author(s): 岡本仁
  • Organizer: 14th IBRO-APRC associate school of neuroscience "Synaptic plasticity : From basics to clinical applications"
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2010-01-27
• [Presentation] ゼブラフィッシュ研究から見たヒトの心の成り立ち (2010)
  • Author(s): 岡本仁
  • Organizer: 大阪バイオサイエンス研究所 Monthly Lecture
  • Place of Presentation: 吹田市
  • Year and Date: 2010-01-08
• [Presentation] Zebrafish as a model animal to study neural circuits against fear (2009)
  • Author(s): 岡本仁
  • Organizer: NCF Topical Workshop -Roles of neuroinformatics in the process of building, evaluating and using genetic animal models for brain diseases
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2009-12-13
• [Presentation] 恐怖研究の新しいモデル実験動物としてのゼブラフィッシュ (2009)
  • Author(s): 岡本仁
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-12-10
• [Presentation] Zebrafish as a model system for study of fear (2009)
  • Author(s): 岡本仁
  • Organizer: IBRO-APRC Neuroscience associate school : Hormones, Brain and Behaviour
  • Place of Presentation: Bandar Sunway, Malaysia
  • Year and Date: 2009-11-30
• [Presentation] 手綱核:行動と記憶のスイッチボードを求めて (2009)
  • Author(s): 岡本仁
  • Organizer: 千里ライフサイエンスセミナー「次世代の脳研究」
  • Place of Presentation: 豊中市
  • Year and Date: 2009-11-06
• [Presentation] Roles of Mosaic eyes/Crumbs complex in coordination of proliferation with the a pico-basal polarity of the neuroepithelial cells (2009)
  • Author(s): 岡本仁
  • Organizer: Construction and Reconstruction of the Brain
  • Place of Presentation: 淡路市
  • Year and Date: 2009-10-09
• [Presentation] Functional analysis of the habenula in control of fear (2009)
  • Author(s): 岡本仁
  • Organizer: 4th Asia-Oceania zebrafish meeting
  • Place of Presentation: Jeju island, Korea
  • Year and Date: 2009-09-01
• [Book] 遺伝子と経験が作る神経回路 現代生物科学入門第4巻 (2009)
  • Author(s): 浅島誠, 他編
  • Publisher: 岩波書店
• [Book] 研究をささえるモデル生物:実験室いきものガイド (2009)
  • Author(s): 吉川寛, 他編
  • Publisher: 化学同人