Pharmacogenetic analysis of orexin neuronal projections

• Project/Area Number: 26860157
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Jichi Medical University (2015); Nagoya University (2014)
• Principal Investigator: Inutsuka Ayumu 自治医科大学, 医学部, 助教 (30584776)
• Co-Investigator(Renkei-kenkyūsha): YAMANAKA Akihiro 名古屋大学, 環境医学研究所, 教授 (60323292)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DREADD / オレキシン神経 / 視床下部 / 投射経路 / オレキシン / 薬理遺伝学 / 摂食 / 代謝

Outline of Final Research Achievements

Using orexin-Cre mice and Cre-dependent AAV vectors, we achieved pharmacogenetic activation of orexin neurons. We also achieved selective ablation of orexin neurons using diphtheria toxin fragment A (DTA). Our comprehensive analysis of these transgenic mice revealed a concurrent regulation of sleep/wakefulness, feeding, and metabolism by orexin neurons. In order to manipulate specific orexin neuronal projections, we developed genetic tools for retrograde transport of Cre recombinase.

Research Products

• [Journal Article] Insular neural system controls decision-making in healthy and methamphetamine-treated rats (2015)
  • Author(s): Mizoguchi H, Katahira K, Inutsuka A, Fukumoto K, Nakamura A, Wang T, Nagai T, Sato J, Sawada M, Ohira H,Yamanaka A, Yamada K
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 (29) Issue: 29 Pages: 3930-3939
  • DOI: 10.1073/pnas.1418014112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A top-down cortical circuit for accurate sensory perception (2015)
  • Author(s): Manita S, Suzuki T, Homma C, Matsumoto T, Odagawa M, Yamada K, Ota K, Matsubara C, Inutsuka A, Sato M, Ohkura M, Yamanaka A, Yanagawa Y, Nakai J, Hayashi Y, Larkum ME, Murayama M
  • Journal Title: Neuron Volume: 86(5) Issue: 5 Pages: 1304-16
  • DOI: 10.1016/j.neuron.2015.05.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Atomistic design of microbial opsin-based blue-shifted optogenetics tools (2015)
  • Author(s): Kato HE, Kamiya M, Sugo S, Ito J, Taniguchi R, Orito A, Hirata K, Inutsuka A,Yamanaka A, Maturana AD, Ishitani R, Sudo Y, Hayashi S, Nureki O
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 7177-7177
  • DOI: 10.1038/ncomms8177
  • NAID: 120005745621
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. (2014)
  • Author(s): Tsunematsu T, Ueno T, Tabuchi S, Inutsuka A, Tanaka KF, Hasuwa H, Kilduff TS, Terao A, Yamanaka A.
  • Journal Title: Journal of Neuroscience Volume: 34 Issue: 20 Pages: 6896-6909
  • DOI: 10.1523/jneurosci.5344-13.2014
  • Peer Reviewed / Open Access
• [Journal Article] Concurrent and robust regulation of feeding behavions and metabolism by orexin neurons. (2014)
  • Author(s): Inutsuka A, Inui A, Tabuchi S, Tsunematsu T, Lazarus M.
  • Journal Title: Neuropharmacology Volume: 85 Pages: 451-460
  • DOI: 10.1016/j.neuropharm.2014.06.015
  • Peer Reviewed / Open Access
• [Journal Article] Vangl2 regulates E-cadherin in epithelial cells. (2014)
  • Author(s): Nagaoka, T., Inutsuka, A., Begum, K., Bin hafiz, K. & Kishi, M.
  • Journal Title: Scientific reports Volume: 4 Issue: 1 Pages: 6940-6940
  • DOI: 10.1038/srep06940
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Correlative activity and physiological role of orexin neurons in nociception (2015)
  • Author(s): 犬束歩、山下哲、田口徹、チョドリスリカンタ、山中章弘
  • Organizer: 包括型脳科学研究推進支援ネットワーク 平成27 年度 冬のシンポジウム
  • Place of Presentation: 東京都・千代田区
  • Year and Date: 2015-12-18
• [Presentation] The integrative role of orexin neurons in nociception and analgesia (2015)
  • Author(s): Ayumu Inutsuka, Akira Yamashita, Srikanta Chowdhury, Junichi Nakai, Masamichi Okura, Toru Taguchi, Akihiro Yamanaka
  • Organizer: THE 12TH NIKKO INTERNATIONAL SYMPOSIUM 2015 FRONTIERS IN TRANSLATIONAL NEUROSCIENCE
  • Place of Presentation: 栃木県・下野市
  • Year and Date: 2015-11-20
  • Int'l Joint Research
• [Presentation] オレキシン神経は痛み刺激に応じて活動し、侵害受容を調節する (2015)
  • Author(s): 犬束歩、山下哲、田口徹、チョドリスリカンタ、山中章弘
  • Organizer: 第３８回 日本神経科学大会
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2015-07-29
• [Presentation] The physiological role of orexin neurons in feeding and metabolism revealed by pharmacogenetic activation and chronic ablation (2014)
  • Author(s): Inutsuka A, Inui A, Tabuchi S, Lazarus M, Yamanaka A.
  • Organizer: Neuroscience 2014 Annual Meeting
  • Place of Presentation: Washington, D.C.
  • Year and Date: 2014-11-19
• [Presentation] オレキシン神経特異的な活動操作・細胞死誘導による、摂食・代謝調節機構の解析 (2014)
  • Author(s): 犬束 歩、乾 あずさ、田淵 紗和子、常松 友美、Michael Lazarus、山中 章弘
  • Organizer: 第６１回中部日本生理学会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-08
• [Presentation] 薬理遺伝学的手法を用いたオレキシン神経の機能解析 (2014)
  • Author(s): 犬束 歩
  • Organizer: 平成26年度生理学研究所研究会 グリア細胞機能から迫る脳機能解明
  • Place of Presentation: 岡崎
  • Year and Date: 2014-10-24
  • Invited
• [Presentation] Pharmacogenetic analysis of concurrent regulation of feeding and metabolism by orexin neurons (2014)
  • Author(s): Inutsuka A, Inui A, Tabuchi S, Lazarus M, Yamanaka A.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-13
• [Book] 分子脳科学: 分子から脳機能と心に迫る (2015)
  • Author(s): 三品 昌美
  • Total Pages: 291
  • Publisher: 化学同人
• [Book] プログレッシブ生命科学 (第7章 2.時間単位のリズム) (2014)
  • Author(s): 犬束歩、山中章弘
  • Publisher: 南山堂
• [Patent(Industrial Property Rights)] 投射経路選択的な遺伝子発現制御 (2014)
  • Inventor(s): 山中章弘、犬束歩
  • Industrial Property Rights Holder: 山中章弘、犬束歩
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-04-30