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Neuronal mechanisms that regulate hyper-arousal in response to stress and anxiety

Research Project

Project/Area Number 15H03122
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic / Social brain science
Research InstitutionUniversity of Tsukuba (2016-2017)
Kanazawa University (2015)

Principal Investigator

Sakurai Takeshi  筑波大学, 医学医療系, 教授 (60251055)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords覚醒 / 情動 / 大脳辺縁系 / オレキシン / 不安 / 分界条床核 / 不眠 / ストレス / 睡眠 / 不眠障害 / 過覚醒 / 視床下部
Outline of Final Research Achievements

We found that acute optogenetic excitation of GABA neurons in the BNST during non-rapid eye movement (NREM) sleep in mice resulted in immediate transition to a wakefulness state without the function of orexins. Prolonged excitation of GABABNST neurons by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, which was abolished by pre-administration of a dual orexin receptor antagonist. We also found that when the orexin→NA→amygdala circuit was artificially activated, fear-related behavior increased in a similar but distinct from the training context. Increased activation of these circuits enhanced the fear response in otherwise neutral situation. Conditions that naturally activate orexin neurons, such as fasting, could result in an orexin-dependent shift to a ‘vigilance’ state and alter the selection of a behavioral response to avoid and handle environmental threats.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (39 results)

All 2018 2017 2016 2015 Other

All Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 7 results,  Invited: 11 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Orexin modulates behavioral fear expression through the locus coeruleus2017

    • Author(s)
      Soya Shingo、Takahashi Tohru M.、McHugh Thomas J.、Maejima Takashi、Herlitze Stefan、Abe Manabu、Sakimura Kenji、Sakurai Takeshi
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1606-1606

    • DOI

      10.1038/s41467-017-01782-z

    • NAID

      120007128779

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Orexin Receptor Multimerization versus Functional Interactions: Neuropharmacological Implications for Opioid and Cannabinoid Signalling and Pharmacogenetics2017

    • Author(s)
      Thompson Miles、Sakurai Takeshi、Rainero Innocenzo、Maj Mary、Kukkonen Jyrki
    • Journal Title

      Pharmaceuticals

      Volume: 10 Issue: 4 Pages: 79-79

    • DOI

      10.3390/ph10040079

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] xcitation of GABAergic neurons in the bed nucleus of the stria terminalis triggers immediate transition from non-rapid eye movement sleep to wakefulness in mice.2017

    • Author(s)
      Shota Kodani, Shingo Soya and Takeshi Sakurai
    • Journal Title

      Journal of Neuroscience

      Volume: 37 Issue: 30 Pages: 7164-7176

    • DOI

      10.1523/jneurosci.0245-17.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models2017

    • Author(s)
      Irukayama-Tomobe Y, Ogawa Y, Tominaga H, Ishikawa Y, Hosokawa N, Ambai S, Kawabe Y, Uchida S, Nakajima R, Saitoh T, Kanda T, Vogt K, Sakurai T, Nagase H, Yanagisawa M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114 Issue: 22 Pages: 5731-5736

    • DOI

      10.1073/pnas.1700499114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fine-Tuning Circadian Rhythms: The Importance of Bmal1 Expression in the Ventral Forebrain.2017

    • Author(s)
      Mieda M, Hasegawa E, Kessaris N, Sakurai T
    • Journal Title

      Front Neurosci.

      Volume: 11 Pages: 55-55

    • DOI

      10.3389/fnins.2017.00055

    • NAID

      120006027787

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serotonin neurons of the dorsal raphe mediate the anti-cataplectic action of orexin neurons by reducing the amygdala activity2017

    • Author(s)
      Hasegawa, E., Maejima, T., Yoshida, T., Masseck O.A., Herlitze, S., Yoshioka, M., Sakurai, T., Mieda, M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114 Issue: 17

    • DOI

      10.1073/pnas.1614552114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serotonin neurons of the dorsal raphe mediate the anti-cataplectic action of orexin neurons by reducing the amygdala activity2017

    • Author(s)
      Hasegawa, E., Maejima, T., Yoshida, T., Masseck O.A., Herlitze, S., Yoshioka, M., Sakurai, T., Mieda, M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Odour-induced analgesia mediated by hypothalamic orexin neurons in mice.2016

    • Author(s)
      Tashiro S, Yamaguchi R, Ishikawa S, Sakurai T, Kajiya K, Kanmura Y, Kuwaki T, Kashiwadani H.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 37129-37129

    • DOI

      10.1038/srep37129

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] QRFP-deficient mice are hypophagic, lean, hypoactive and exhibit increased anxiety-like behavior2016

    • Author(s)
      Okamoto K, Yamasaki M, Takao K, Soya S, Iwasaki M, Sasaki K, Magoori K, Sakakibara I, Miyakawa T, Mieda M, Watanabe M, Sakai J, Yanagisawa M, Sakurai T
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 11 Pages: e0164716-e0164716

    • DOI

      10.1371/journal.pone.0164716

    • NAID

      120007129233

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.2016

    • Author(s)
      Mieda M, Okamoto H, Sakurai T.
    • Journal Title

      Curr Biol.

      Volume: S0960-9822(16) Issue: 18 Pages: 30773-4

    • DOI

      10.1016/j.cub.2016.07.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sleep Control, GPCRs, and Glucose Metabolism.2016

    • Author(s)
      Tsuneki H, Sasaoka T, Sakurai T.
    • Journal Title

      Trends Endocrinol Metab.

      Volume: 27(9) Issue: 9 Pages: 633-42

    • DOI

      10.1016/j.tem.2016.06.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive Behavioral Analysis of Male Ox1r (-/-) Mice Showed Implication of OrexinReceptor-1 in Mood, Anxiety, and Social Behavior.2015

    • Author(s)
      Abbas MG, Shoji H, Soya S, Hondo M, Miyakawa T, Sakurai T.
    • Journal Title

      Front Behav Neurosci.

      Volume: 9 Pages: 324-324

    • DOI

      10.3389/fnbeh.2015.00324

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nighttime Administration of Nicotine Improves Hepatic Glucose Metabolism via the Hypothalamic Orexin System in Mice.2015

    • Author(s)
      Tsuneki H, Nagata T, Fujita M, Kon K, Wu N, Takatsuki M, Yamaguchi K, Wada T, Nishijo H, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Endocrinology

      Volume: 157 Pages: 195-206

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypocretin/orexin prevents recovery from sickness.2015

    • Author(s)
      Tanaka S, Toyoda H, Honda Y, Seki Y, Sakurai T, Honda K, Kodama T.
    • Journal Title

      Biomed Rep.

      Volume: 3 Pages: 648-650

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Messenger RNA expression profile of sleep-related genes in peripheral blood cells in patients with chronic kidney disease.2015

    • Author(s)
      Kitajima S, Iwata Y, Furuichi K, Sagara A, Shinozaki Y, Toyama T, Sakai N, Shimizu M, Sakurai T, Kaneko S, Wada T.
    • Journal Title

      Clin Exp Nephrol

      Volume: 20 Issue: 2 Pages: 218-25

    • DOI

      10.1007/s10157-015-1150-y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies.2015

    • Author(s)
      Nishizawa D et al.
    • Journal Title

      Mol Brain.

      Volume: 8 Issue: 1 Pages: 50-50

    • DOI

      10.1186/s13041-015-0142-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular clocks in AVP neurons of the SCN are critical for interneuronal coupling regulating circadian behavior rhythm.2015

    • Author(s)
      Mieda M, Ono D, Hasegawa E, Okamoto H, Honma K, Honma S, Sakurai T.
    • Journal Title

      Neuron

      Volume: 85 Pages: 1103-1116

    • Related Report
      2015 Annual Research Report
  • [Presentation] Roles of Orexin Neurons at the Interface of Systems that regulate Emotion and Arousal/Vigilance The 8th International Society of Radiation Neurobiology Conference2018

    • Author(s)
      Takeshi Sakurai
    • Organizer
      The 8th International Society of Radiation Neurobiology Conference ISRN-2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 大脳辺縁系と覚醒系を結ぶオレキシンの役割2018

    • Author(s)
      櫻井 武
    • Organizer
      第 95 回日本生理学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Neural circuits of orexin neurons:interface of systems of emotion and arousal/vigilance.2017

    • Author(s)
      Takeshi Sakurai
    • Organizer
      The 6th Annual IIIS Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The Mechanism of Narcolepsy: what it tells on clinical perspective2017

    • Author(s)
      Takeshi Sakurai
    • Organizer
      2nd International Taiwanese Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] オレキシンによる覚醒と行動の制御機構2017

    • Author(s)
      櫻井 武
    • Organizer
      日本睡眠学会第42回定期学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] オレキシンは青斑核に働き情動行動を増強する2017

    • Author(s)
      櫻井 武,征矢 晋吾,高橋 徹,前島 隆司
    • Organizer
      第94回日本生理学大会日本神経内分泌学会連携シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] セロトニンによるオレキシンニューロンの制御が睡眠・覚醒状態に与える影響2016

    • Author(s)
      齊藤夕貴、前島隆司、辻野なつ子、阿部学、崎村建司、櫻井 武
    • Organizer
      日本睡眠学会第41回定期学術集会
    • Place of Presentation
      京王プラザホテル 東京都新宿区
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] レキシンは扁桃体へのノルアドレナリン入力を制御し恐怖行動の発現に関与する2016

    • Author(s)
      征矢晋吾、前島隆司、桜井 武
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス脳におけるヒスタミン作動性神経細胞に直接シナプス入力を送る神経細胞のマッピング2016

    • Author(s)
      前島隆司、西谷光広、齋藤夕貴、櫻井 武
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] オレキシン産生ニューロンの抗カタプレキシー作用は背側縫線核・セロトニン作動性ニューロンの扁桃体抑制により仲介される2016

    • Author(s)
      長谷川恵美、前島隆司、櫻井 武、三枝理博
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 視床下部外側野のオレキシンニューロンへ直接入力する神経の同定2016

    • Author(s)
      4.齊藤夕貴、前島隆司、櫻井 武
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Orexins and Orexin Receptors in the Regulation of Sleep and Wakefulness.2016

    • Author(s)
      Takeshi Sakurai
    • Organizer
      The Sixteenth Conference of Peace through Mind/Brain Science
    • Place of Presentation
      Hamamatsu, Japan
    • Year and Date
      2016-02-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural Circuits of Orexin Neurons: Interface of Systems of Emotion, Energy Homeostasis and Arousal.2016

    • Author(s)
      Takeshi Sakurai
    • Organizer
      30th CINP World Congress of Neuropsychopharmacology Satellite Symposium
    • Place of Presentation
      COEX Convention Center, Korea、ソウル市、韓国
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural circuit of orexin neurons, and its role in regulating the sleep/wakefulness states2015

    • Author(s)
      Takeshi Sakurai
    • Organizer
      IBRO-Kemali School 2015
    • Place of Presentation
      Institute of Biomolecular Chemistry of CNR, Pozzuoli, Italy
    • Year and Date
      2015-09-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of adult born neurons during sleep.2015

    • Author(s)
      Sakaguchi, M., Kumar, D., Hayashi, M., Yu, L.M., McHugh, T.J., Sakurai, T.
    • Organizer
      The 38th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] rexin neurons suppress narcolepsy via 2 distinct efferent pathways.2015

    • Author(s)
      Hasegawa, E., Yanagisawa, M., Sakurai, T., Mieda, M.
    • Organizer
      The 38th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Cellular clocks in AVP neurons of the SCN are critical for interneuronal coupling regulating circadian behavior thythm.2015

    • Author(s)
      Mieda, M., Ono, D., Hasegawa, E., Okamoto, H., Honma, K., Honma, S., Sakurai, T.
    • Organizer
      The 38th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Orexins and orexin receptors in the regulation of sleep and wakefulness.2015

    • Author(s)
      Sakurai, T.
    • Organizer
      rd Alpine Sleep Summer School 2015
    • Place of Presentation
      Lugano-Switzerland
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 視交叉上核バソプレシン産生ニューロンの細胞時計はニューロン間カップリングの調節を通して概日行動リズムを制御する2015

    • Author(s)
      三枝理博、小野大輔、長谷川恵美、岡本仁、本間研一、本間さと、櫻井 武
    • Organizer
      第12回GPCR研究会
    • Place of Presentation
      未来館ホール お台場
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 睡眠の科学・改訂新版 なぜ眠るのか なぜ目覚めるのか2017

    • Author(s)
      櫻井 武
    • Total Pages
      264
    • Publisher
      講談社
    • ISBN
      4065020263
    • Related Report
      2017 Annual Research Report
  • [Book] 睡眠障害のなぞを解く 「眠りのしくみ」から「眠るスキル」まで2015

    • Author(s)
      櫻井 武
    • Total Pages
      144
    • Publisher
      講談社
    • Related Report
      2015 Annual Research Report
  • [Remarks] http://sakurai-lab.com/

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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