神経性調節学 - 器官系機能調節学(協力) - 研究室紹介 | 名古屋大学大学院医学系研究科・医学部医学科

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器官系機能調節学(協力)神経性調節学

研究室概要

本研究室では、主にマウスをモデル動物として、動物行動の基盤となる神経回路機構を研究しています。特に、睡眠覚醒や摂食行動など本能行動を調節する視床下部神経回路の機能は研究室の中心テーマになっています。様々な遺伝子改変動物やウイルスベクターを作成・利用して、オプトジェネティクス(光遺伝学)やDREADD(薬理遺伝学)などの最新の神経活動操作技術や運命制御などによって摂動を与え、その結果表出する動物個体の行動・生理の変化を多角的に解析しています。分子から動物個体までを幅広く扱い、分子・細胞・シナプスレベルでの現象と神経回路機能・行動発現を繋げることで、動物行動の動作原理の統合的理解と疾患との関連について明らかにすることが目標です。

研究プロジェクト

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1. 視床下部神経による本能行動と生体恒常性の制御機構の解明

視床下部にあり神経ペプチドを産生する神経細胞は、睡眠覚醒などの本能行動や生体恒常性の制御において重要な役割を担っています。これまでに、スライス・パッチクランプ法を用いた視床下部オレキシン神経細胞からの記録によって、入力神経と応答様式について明らかにし、睡眠覚醒調節に関わる神経回路を同定してきました。また、光遺伝学を用いてオレキシン神経活動を制御したときの睡眠覚醒状態変化を調べることによって神経回路の動作原理について明らかにしてきました。現在では、オレキシン神経のみならず、視床下部のメラニン凝集ホルモン(MCH)神経の機能や、その上流・下流にある神経細胞群の応答様式や生理機能についても研究を進めています。

これまでの代表的な成果:Science 365:1308-1313 (2019); Science 352, 1315-1318 (2016); J. Neurosci. 34, 6896-6909 (2014): J. Neurosci. 34, 6495-6509 (2014); J. Neurosci. 31, 10529-10539 (2011); Neuron 38, 701-713 (2003)

2. 概日時計による行動・生理機能のタイミングを決める神経メカニズム

私たちは、時刻や光の情報が一切ない部屋で生活をしても、睡眠・覚醒や体温はおよそ24時間周期で変動します。このおよそ24時間のリズムを「概日リズム」と呼び、「概日時計」がその調節を担います。動物が1日のうち最適な時間に睡眠、繁殖、摂食などを行う事は、地球上で種を残すための極めて重要な生存戦略の1つです。また動物は季節により、繁殖機能や生理機能を劇的に変化させることで、厳しい環境を乗り越えています。しかし、これらの動物行動や生理機能のタイミングを調節する神経メカニズムはよくわかっていません。私たちの研究チームは、動物が示す行動や生理機能のタイミングを調節する、神経回路の動作原理の理解を目指しています。そのため、光操作や光イメージングや電気生理学、組織学、動物行動学に加え、ウイルスベクターやin vivoゲノム編集等の技術を総動員し、概日時計の中枢である視床下部に位置する「視交叉上核」を起点とした脳内神経ネットワークの全貌解明を目標とします。詳しくは以下個別HPをご参照ください。https://daiono14.wixsite.com/circadianrhythm

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これまでの代表的な成果: Ono et al., 2020 Science Advances, Ono et al., 2019 Communications Biology, Ono et al., 2017 PNAS, Ono et al., 2016 Science Advances, Ono et al., 2013 Nature Communications

教員

構成員名役職所属
山中 章弘 教授 環境医学研究所 ストレス受容・応答研究部門 神経系分野II
小野 大輔 講師 環境医学研究所 ストレス受容・応答研究部門 神経系分野II
山口 裕嗣 特任助教 環境医学研究所 ストレス受容・応答研究部門 神経系分野II

研究実績

  • 2021年
    1. Yamashita A, Moriya S, Nishi R, Kaminosono J,Yamanaka A, Kuwaki T*. Aversive emotion rapidly activates orexin neurons and increases heart rate in freely moving mice. Mol Brain 14(1):104 (2021)
    2. Matsubara T, Yanagida T, Kawaguchi N, Nakano T, Yoshimoto J, Sezaki M, Takizawa H, Tsunoda SP, Horigane SI, Ueda S, Takemoto-Kimura S, Kandori H,Yamanaka A, Yamashita T*.Remote control of neural function by X-ray-induced scintillation. Nat Commun 12(1):4478 (2021)
    3. Izawa S, Yoneshiro T, Kondoh K, Nakagiri S, Okamatsu-Ogura Y, Terao A, Minokoshi Y,Yamanaka A, Kimura K. J Physiol (in press)2021
    4. Ohmura Y, Iwami K, Chowdhury S, Sasamori H, Sugiura C, Bouchekioua Y, Nishitani N,Yamanaka A, Yoshioka M. Disruption of model-based decision making by silencing of serotonin neurons in the dorsal raphe nucleus. Curr Biol 31(11):2446-2454.(2021)
    5. Coffey AA, Joyal AA, Yamanaka A, Scammell TE*.The impacts of age and sex in a mouse model of childhood narcolepsy. Front Neurosci 15:644757 (2021)
    6. Kato Y*, Katsumata H*, Inutsuka A, Yamanaka A, Onaka T, Minami S, Orikasa C. Involvement of MCH-oxytocin neural relay within the hypothalamus in murine nursing behavior. Sci Rep 11(1):3348 (2021)
    7. Lin YH, Yamahashi Y, Kuroda K, Faruk MO, Zhang X, Yamada K, Yamanaka A, Nagai T, Kaibuchi K. Accumbal D2R-medium spiny neurons 1 regulate aversive behaviors 2 through PKA-Rap1 pathway. Neurochem Int 143:104935.(2021)
    8. Setsu T, Hamada Y, Oikawa D, Mori T, Ishiuji Y, Sato D, Narita M, Miyazaki S, Furuta E, Suda Y, Sakai H, Ochiya T, Tezuka H, Iseki M, Inada E, Yamanaka A, Kuzumaki N, Narita M. Direct evidence that the brain reward system is involved in the control of scratching behaviors induced by acute and chronic itch. Biochem Biophys Res Commun S0006-291X(20)32067-2. (2021)
  • 2020年
    1. Horii-Hayashi N, Nomoto K, Endo N, Yamanaka A, Kikusui T, Nishi M. Hypothalamic Perifornical Urocortin-3 Neurons Modulate Defensive Responses to a Potential Threat Stimulus. iScience 24(1):101908.(2020)
    2. Miyazaki K*, Miyazaki KW, Yamanaka A, Sivori G, Tanaka KF, Doya K. Serotonergic projections to the orbitofrontal and medial prefrontal cortices differentially modulate waiting for future rewards. Sci Adv 6(48):eabc7246. (2020) 
    3. Ono D, Sugiyama T, Mukai Y, Yamanaka A, Hung CJ, Chowdhury S. The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus. Sci Adv 6(45):eabd0384.(2020)
    4. Ito H, Yokoi D, Kobayashi R, Okada H, Kajita Y, Okuda S.The relationships between three-axis accelerometer measures of physical activity and motor symptoms in patients with Parkinson's disease: a single-center pilot study. BMC Neurol 20(1): 340 (2020)
    5. Li SB, Borniger JC, Yamaguchi H, Hedou J, Gaudilliere B, *de Lecea L.Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression.Sci Adv 6(37):eabc2590.
    6. Mukai Y, Nagayama A, Itoi K, Yamanaka A.*Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus. Sci Rep 10(1): 13639 (2020)
    7. Kawatani M, Itoi K, Talukder AH, Uchida K, Sakimura K, *Kawatani M. Cholinergic modulation of CRH and non-CRH neurons in Barrington's nucleus of the mouse. J Neurophysiol 124(2): 443-457. (2020)
    8. Kojima K, Miyoshi N, Shibukawa A, Chowdhury S, Tsujimura M, Noji T, Ishikita H, Yamanaka A, Sudo Y. A Green-Sensitive, Long-Lived and Step-Functional Anion Channelrhodopsin-2 Variant as a High-Potential Neural Silencing Tool.J Phys Chem Lett 11: 6214-6218 (2020)
    9. Yoshida K, Tsutsui-Kimura I, Kono A, Yamanaka A, Kobayashi K, Watanabe M, Mimura M, Tanaka KF: Opposing ventral striatal medium spiny neuron activities are shaped by striatalparvalbumin-expressing interneurons during goal-directed behaviors. Cell Rep 31(13):107829 (2020)
    10. Wang HY, Eguchi K, Yamashita T, Takahashi T: Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. J Neurosci 40: 4103-4115(2020)
    11. Abe C*, Yamaoka Y, Maejima Y, Mikami T, Yokota S, Yamanaka A, Morita H*: VGLUT2-expressing neurons in the vestibular nuclear complex mediate gravitational stress-induced hypothermia in mice. Commun Biol 3(1): 227 (2020)
    12. Moriya S*, Yamashita A, Masukawa D, Setoyama H, Hwang Y, Yamanaka A, Kuwaki T: Involvement of A13 dopaminergic neurons located in the zona incerta in nociceptive processing: a fiber photometry study. Mol Brain 13(1):60 (2020)
    13. Flanigan ME, Aleyasin H, Li L, Burnett CJ, Chan KL, LeClair KB, Lucas EK, Matikainen-Ankney B, Durand-de Cuttoli R, Takahashi A, Menard C, Pfau ML, Golden SA, Bouchard S, Calipari ES, Nestler EJ, DiLeone RJ, Yamanaka A, Huntley GW, Clem RL, *Russo SJ: Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice. Nat Neurosci 23(5): 638-650 (2020)
    14. Hung CJ, Ono D, Kilduff TS, Yamanaka A*: Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy. eLife 9:e54275.(2020)
    15. Nagai Y,Takayama K, Nishitani N, Andoh C, Koda M, Shirakawa H, Nakagawa T, Nagayasu K* ,Yamanaka A, Kaneko S*: The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion. Int J Mol Sci 21(6). pii: E2160. (2020)
    16. Imayoshi I, Tabuchi S, Matsumoto M, Kitano S, Miyachi H, Kageyama R, Yamanaka A: Light-induced silencing of neural activity in Rosa26 knock-in and BAC transgenic mice conditionally expressing the microbial halorhodopsin eNpHR3. Sci Rep 10(1):3191(2020)  
    17. Moriya S, Yamashita A, Masukawa D, Kambe Y, Sakaguchi J, Setoyama H, Yamanaka A, Kuwaki T: Involvement of supralemniscal nucleus (B9) 5-HT neuronal system in nociceptive processing: a fiber photometry study. Mol Brain 13(1):14 (2020)
    18. Wada S, Yanagida J, Sasase H, Zhang T, Li X, Kamii H, Domoto M, Deyama S, Hinoi E, Yamanaka A, Nishitani N, Nagayasu K, Kaneko S, Minami M, *Kaneda K: Acute restraint stress augments the rewarding memory of cocaine through activation of α1 adrenoceptors in the medial prefrontal cortex of mice. Neuropharmacology 166:107968 (2020)  
    19. Zhang T, Yanagida J, Kamii H, Wada S, Domoto M, Sasase H, Deyama S, Takarada T, Hinoi E, Sakimura K, Yamanaka A, Maejima T, Mieda M, Sakurai T, Nishitani N, Nagayasu K, Kaneko S, Minami M, Kaneda K: Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice. Addict Biol25(1):e12723 (2020)
  • 2019年
    1. Liang L, Teh DBL, Dinh ND, Chen W, Chen Q, Wu Y, Chowdhury S, Yamanaka A, Sum TC, Chen CH, Thakor NV, All AH, Liu X. Upconversion amplification through dielectric superlensing modulation. Nat Commun, 2019; 10: 1391.
    2. Lee JW, Hirota T, Ono D, Honma S, Honma KI, Park K, Kay SA. Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase Ialpha and delta. J Med Chem, 2019; 62: 1989-1998.
    3. Macpherson T, Mizoguchi H, Yamanaka A, Hikida T. Preproenkephalin-expressing ventral pallidal neurons control inhibitory avoidance learning. Neurochem Int, 2019; 126: 11-18.
    4. Murata K, Kinoshita T, Fukazawa Y, Kobayashi K, Yamanaka A, Hikida T, Manabe H, Yamaguchi M. Opposing Roles of Dopamine Receptor D1- and D2-Expressing Neurons in the Anteromedial Olfactory Tubercle in Acquisition of Place Preference in Mice. Front Behav Neurosci, 2019; 13: 50.
    5. Chowdhury S, Hung CJ, Izawa S, Inutsuka A, Kawamura M, Kawashima T, Bito H, Imayoshi I, Abe M, Sakimura K, Yamanaka A. Dissociating orexin-dependent and -independent functions of orexin neurons using novel Orexin-Flp knock-in mice. Elife, 2019; 8.
    6. Chowdhury S, Matsubara T, Miyazaki T, Ono D, Fukatsu N, Abe M, Sakimura K, Sudo Y, Yamanaka A. GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice. Elife, 2019; 8.
    7. Moriya S, Yamashita A, Nishi R, Ikoma Y, Yamanaka A, Kuwaki T. Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice. IBRO Rep, 2019; 7: 1-9.
    8. Yamanashi T, Maki M, Kojima K, Shibukawa A, Tsukamoto T, Chowdhury S, Yamanaka A, Takagi S, Sudo Y. Quantitation of the neural silencing activity of anion channelrhodopsins in Caenorhabditis elegans and their applicability for long-term illumination. Sci Rep, 2019; 9: 7863.
    9. Ono D, Honma K-i, Yanagawa Y, Yamanaka A, Honma S. GABA in the suprachiasmatic nucleus refines circadian output rhythms in mice. Communications Biology, 2019; 2: 232.
    10. Matsubara T, Hayashi K, Wakatsuki K, Abe M, Ozaki N, Yamanaka A, Mizumura K, Taguchi T. Thin-fibre receptors expressing acid-sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise. Eur J Pain, 2019; 23: 1801-1813.
    11. Izawa S, Chowdhury S, Miyazaki T, Mukai Y, Ono D, Inoue R, Ohmura Y, Mizoguchi H, Kimura K, Yoshioka M, Terao A, Kilduff TS, Yamanaka A. REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories. Science, 2019; 365: 1308-1313.
    12. Sugiyama E, Kondo T, Kuzumaki N, Honda K, Yamanaka A, Narita M, Suematsu M, Sugiura Y. Mechanical allodynia induced by optogenetic sensory nerve excitation activates dopamine signaling and metabolism in medial nucleus accumbens. Neurochem Int, 2019; 129: 104494.
    13. Nishitani N, Ohmura Y, Nagayasu K, Shibui N, Kaneko S, Ohashi A, Yoshida T, Yamanaka A, Yoshioka M. CRISPR/Cas9-mediated in vivo gene editing reveals that neuronal 5-HT1A receptors in the dorsal raphe nucleus contribute to body temperature regulation in mice. Brain Res, 2019; 1719: 243-252.
    14. Williams RH, Tsunematsu T, Thomas AM, Bogyo K, Yamanaka A, Kilduff TS. Transgenic Archaerhodopsin-3 Expression in Hypocretin/Orexin Neurons Engenders Cellular Dysfunction and Features of Type 2 Narcolepsy. J Neurosci, 2019; 39: 9435-9452.
    15. Ito H, Yokoi S, Yokoyama K, Asai T, Uda K, Araki Y, Takasu S, Kobayashi R, Okada H, Okuda S. Progressive stenosis and radiological findings of vasculitis over the entire internal carotid artery in moyamoya vasculopathy associated with graves' disease: a case report and review of the literature. BMC Neurol, 2019, 19(1):34.
  • 2018年
    1. Futatsuki T, Yamashita A, Ikbar KN, Yamanaka A, Arita K, Kakihana Y, Kuwaki T. Involvement of orexin neurons in fasting- and central adenosine-induced hypothermia. Sci Rep, 2018; 8: 2717.
    2. Suda Y, Kuzumaki N, Narita M, Hamada Y, Shibasaki M, Tanaka K, Tamura H, Kawamura T, Kondo T, Yamanaka A, Narita M. Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors. Biochem Biophys Res Commun, 2018; 496: 1102-1108.
    3. Watanabe M, Narita M, Hamada Y, Yamashita A, Tamura H, Ikegami D, Kondo T, Shinzato T, Shimizu T, Fukuchi Y, Muto A, Okano H, Yamanaka A, Tawfik VL, Kuzumaki N, Navratilova E, Porreca F, Narita M. Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer. Mol Pain, 2018; 14: 1744806918756406.
    4. Watanabe M, Sugiura Y, Sugiyama E, Narita M, Navratilova E, Kondo T, Uchiyama N, Yamanaka A, Kuzumaki N, Porreca F, Narita M. Extracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated system. Mol Pain, 2018; 14: 1744806918754934.
    5. Nasanbuyan N, Yoshida M, Takayanagi Y, Inutsuka A, Nishimori K, Yamanaka A, Onaka T. Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice. Endocrinology, 2018; 159: 763-775.
    6. Kikusui T, Kajita M, Otsuka N, Hattori T, Kumazawa K, Watarai A, Nagasawa M, Inutsuka A, Yamanaka A, Matsuo N, Covington HE, 3rd, Mogi K. Sex differences in olfactory-induced neural activation of the amygdala. Behav Brain Res, 2018; 346: 96-104.
    7. Hashimoto M, Yamanaka A, Kato S, Tanifuji M, Kobayashi K, Yaginuma H. Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus. Front Neural Circuits, 2018; 12: 6.
    8. Ono D, Honma KI, Yanagawa Y, Yamanaka A, Honma S. Role of GABA in the regulation of the central circadian clock of the suprachiasmatic nucleus. J Physiol Sci, 2018.
    9. Yamashita T, Vavladeli A, Pala A, Galan K, Crochet S, Petersen SSA, Petersen CCH. Diverse Long-Range Axonal Projections of Excitatory Layer 2/3 Neurons in Mouse Barrel Cortex. Frontiers in Neuroanatomy, 2018; 12.
    10. Moriya S, Yamashita A, Kawashima S, Nishi R, Yamanaka A, Kuwaki T. Acute Aversive Stimuli Rapidly Increase the Activity of Ventral Tegmental Area Dopamine Neurons in Awake Mice. Neuroscience, 2018; 386: 16-23.
    11. Thannickal TC, John J, Shan L, Swaab DF, Wu MF, Ramanathan L, McGregor R, Chew KT, Cornford M, Yamanaka A, Inutsuka A, Fronczek R, Lammers GJ, Worley PF, Siegel JM. Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy. Sci Transl Med, 2018; 10.
    12. Black SW, Sun JD, Santiago P, Laihsu A, Kimura N, Yamanaka A, Bersot R, Humphries PS. Partial ablation of the orexin field induces a sub-narcoleptic phenotype in a conditional mouse model of orexin neurodegeneration. Sleep, 2018; 41.
    13. Miyazaki K, Miyazaki KW, Yamanaka A, Tokuda T, Tanaka KF, Doya K. Reward probability and timing uncertainty alter the effect of dorsal raphe serotonin neurons on patience. Nat Commun, 2018; 9: 2048.
    14. Koizumi K, Inoue M, Chowdhury S, Bito H, Yamanaka A, Ishizuka T, Yawo H. Functional emergence of a column-like architecture in layer 5 of mouse somatosensory cortex in vivo. J Physiol Sci, 2018.
    15. Ikoma Y, Kusumoto-Yoshida I, Yamanaka A, Ootsuka Y, Kuwaki T. Inactivation of Serotonergic Neurons in the Rostral Medullary Raphe Attenuates Stress-Induced Tachypnea and Tachycardia in Mice. Front Physiol, 2018; 9: 832.
    16. Heiss JE, Yamanaka A, Kilduff TS. Parallel Arousal Pathways in the Lateral Hypothalamus. eNeuro, 2018; 5.
    17. Kondo T, Saito R, Otaka M, Yoshino-Saito K, Yamanaka A, Yamamori T, Watakabe A, Mizukami H, Schnitzer MJ, Tanaka KF, Ushiba J, Okano H. Calcium Transient Dynamics of Neural Ensembles in the Primary Motor Cortex of Naturally Behaving Monkeys. Cell Rep, 2018; 24: 2191-2195.e2194.
    18. Matsui S, Sasaki T, Kohno D, Yaku K, Inutsuka A, Yokota-Hashimoto H, Kikuchi O, Suga T, Kobayashi M, Yamanaka A, Harada A, Nakagawa T, Onaka T, Kitamura T. Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice. Nat Commun, 2018; 9: 4604.
    19. Tokuda IT, Ono D, Honma S, Honma KI, Herzel H. Coherency of circadian rhythms in the SCN is governed by the interplay of two coupling factors. PLoS Comput Biol, 2018; 14: e1006607.
  • 2017年
    1. Black SW, Yamanaka A, Kilduff TS. Challenges in the development of therapeutics for narcolepsy. Prog Neurobiol, 2017; 152: 89-113.
    2. Hayashi K, Katanosaka K, Abe M, Yamanaka A, Nosaka K, Mizumura K, Taguchi T. Muscular mechanical hyperalgesia after lengthening contractions in rats depends on stretch velocity and range of motion. Eur J Pain, 2017; 21: 125-139.
    3. Dergacheva O, Yamanaka A, Schwartz AR, Polotsky VY, Mendelowitz D. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons. Am J Physiol Heart Circ Physiol, 2017; 312: H808-H817.
    4. Enoki R, Oda Y, Mieda M, Ono D, Honma S, Honma KI. Synchronous circadian voltage rhythms with asynchronous calcium rhythms in the suprachiasmatic nucleus. Proc Natl Acad Sci U S A, 2017.
    5. Enoki R, Ono D, Kuroda S, Honma S, Honma KI. Dual origins of the intracellular circadian calcium rhythm in the suprachiasmatic nucleus. Sci Rep, 2017; 7: 41733.
    6. Yamashita T, Yamanaka A. Lateral hypothalamic circuits for sleep-wake control. Curr Opin Neurobiol, 2017; 44: 94-100.
    7. Ono D, Honma S, Nakajima Y, Kuroda S, Enoki R, Honma KI. Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus in parallel with behavioral outputs. Proc Natl Acad Sci U S A, 2017; 114: E3699-E3708.
    8. Ono D, Yamanaka A. Hypothalamic regulation of the sleep/wake cycle. Neurosci Res, 2017; 118: 74-81.
    9. Busse L, Cardin JA, Chiappe ME, Halassa MM, McGinley MJ, Yamashita T, Saleem AB. Sensation during Active Behaviors. J Neurosci, 2017; 37: 10826-10834.
  • 2016年
    1. Branch AF, Navidi W, Tabuchi S, Terao A, Yamanaka A, Scammell TE, Diniz Behn C. Progressive Loss of the Orexin Neurons Reveals Dual Effects on Wakefulness. Sleep, 2016; 39: 369-377.
    2. Dergacheva O, Yamanaka A, Schwartz AR, Polotsky VY, Mendelowitz D. Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons. Neuroscience, 2016; 339: 47-53.
    3. Dergacheva O, Yamanaka A, Schwartz AR, Polotsky VY, Mendelowitz D. Hypoxia and hypercapnia inhibit hypothalamic orexin neurons in rats. J Neurophysiol, 2016; 116: 2250-2259.
    4. Yamashita T, Petersen C. Target-specific membrane potential dynamics of neocortical projection neurons during goal-directed behavior. Elife, 2016; 5.
    5. Ono D, Honma S, Honma K. Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN. Sci Adv, 2016; 2: e1600960.
    6. Chowdhury S, Yamanaka A. Optogenetic activation of serotonergic terminals facilitates GABAergic inhibitory input to orexin/hypocretin neurons. Sci Rep, 2016; 6: 36039.
    7. Inutsuka A, Yamashita A, Chowdhury S, Nakai J, Ohkura M, Taguchi T, Yamanaka A. The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation. Sci Rep, 2016; 6: 29480.
  • 2015年
    1. Taguchi T, Katanosaka K, Yasui M, Hayashi K, Yamashita M, Wakatsuki K, Kiyama H, Yamanaka A, Mizumura K. Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model. Pain, 2015; 156: 415-427.
    2. 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. A Top-Down Cortical Circuit for Accurate Sensory Perception. Neuron, 2015; 86: 1304-1316.
    3. 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. Atomistic design of microbial opsin-based blue-shifted optogenetics tools. Nat Commun, 2015; 6: 7177.
    4. Shibasaki K, Sugio S, Takao K, Yamanaka A, Miyakawa T, Tominaga M, Ishizaki Y. TRPV4 activation at the physiological temperature is a critical determinant of neuronal excitability and behavior. Pflugers Arch, 2015.
    5. Mizoguchi H, Katahira K, Inutsuka A, Fukumoto K, Nakamura A, Wang T, Nagai T, Sato J, Sawada M, Ohira H, Yamanaka A, Yamada K. Insular neural system controls decision-making in healthy and methamphetamine-treated rats. Proc Natl Acad Sci U S A, 2015; 112: E3930-3939.
    6. Ishii K, Kubo K, Endo T, Yoshida K, Benner S, Ito Y, Aizawa H, Aramaki M, Yamanaka A, Tanaka K, Takata N, Tanaka KF, Mimura M, Tohyama C, Kakeyama M, Nakajima K. Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits. J Neurosci, 2015; 35: 12432-12445.
    7. Hososhima S, Yuasa H, Ishizuka T, Hoque MR, Yamashita T, Yamanaka A, Sugano E, Tomita H, Yawo H. Near-infrared (NIR) up-conversion optogenetics. Sci Rep, 2015; 5: 16533.
    8. Black SW, Yamanaka A, Kilduff TS. Challenges in the development of therapeutics for narcolepsy. Prog Neurobiol, 2015.
    9. Fuller PM, Yamanaka A, Lazarus M. How genetically engineered systems are helping to define, and in some cases redefine, the neurobiological basis of sleep and wake. Temperature, 2015; 2: 406-417.
    10. Tokuda Isao T, Ono D, Ananthasubramaniam B, Honma S, Honma K-I, Herzel H. Coupling Controls the Synchrony of Clock Cells in Development and Knockouts. Biophysical Journal, 2015; 109: 2159-2170.
    11. Tsuchiya Y, Minami Y, Umemura Y, Watanabe H, Ono D, Nakamura W, Takahashi T, Honma S, Kondoh G, Matsuishi T, Yagita K. Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse. Genes Cells, 2015; 20: 992-1005.
    12. Ono D, Honma S, Honma K. Circadian PER2::LUC rhythms in the olfactory bulb of freely moving mice depend on the suprachiasmatic nucleus but not on behaviour rhythms. Eur J Neurosci, 2015; 42: 3128-3137.
    13. Ono D, Honma K, Honma S. Circadian and ultradian rhythms of clock gene expression in the suprachiasmatic nucleus of freely moving mice. Sci Rep, 2015; 5: 12310.
    14. Mieda M, Ono D, Hasegawa E, Okamoto H, Honma K-i, Honma S, Sakurai T. Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm. Neuron, 2015; 85: 1103-1116.
  • 2014年
    1. Ohmura Y, Tanaka KF, Tsunematsu T, Yamanaka A, Yoshioka M. Optogenetic activation of serotonergic neurons enhances anxiety-like behaviour in mice. Int J Neuropsychopharmacol, 2014: 1-7.
    2. Tsunematsu T, Ueno T, Tabuchi S, Inutsuka A, Tanaka KF, Hasuwa H, Kilduff TS, Terao A, Yamanaka A. Optogenetic Manipulation of Activity and Temporally Controlled Cell-Specific Ablation Reveal a Role for MCH Neurons in Sleep/Wake Regulation. J Neurosci, 2014; 34: 6896-6909.
    3. Tabuchi S, Tsunematsu T, Black SW, Tominaga M, Maruyama M, Takagi K, Minokoshi Y, Sakurai T, Kilduff TS, Yamanaka A. Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J Neurosci, 2014; 34: 6495-6509.
    4. Black SW, Morairty SR, Chen TM, Leung AK, Wisor JP, Yamanaka A, Kilduff TS. GABAB Agonism Promotes Sleep and Reduces Cataplexy in Murine Narcolepsy. J Neurosci, 2014; 34: 6485-6494.
    5. Takayama Y, Shibasaki K, Suzuki Y, Yamanaka A, Tominaga M. Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1. Faseb j, 2014; 28: 2238-2248.
    6. Beppu K, Sasaki T, Tanaka KF, Yamanaka A, Fukazawa Y, Shigemoto R, Matsui K. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron, 2014; 81: 314-320.
    7. Inutsuka A, Inui A, Tabuchi S, Tsunematsu T, Lazarus M, Yamanaka A. Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons. Neuropharmacology, 2014.
    8. Miyazaki KW, Miyazaki K, Tanaka KF, Yamanaka A, Takahashi A, Tabuchi S, Doya K. Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. Curr Biol, 2014; 24: 2033-2040.
  • 2013年
    1. Tabuchi S, Tsunematsu T, Kilduff TS, Sugio S, Xu M, Tanaka KF, Takahashi S, Tominaga M, Yamanaka A. Influence of inhibitory serotonergic inputs to orexin/hypocretin neurons on the diurnal rhythm of sleep and wakefulness. Sleep, 2013; 36: 1391-1404.
    2. Tsujino N, Tsunematsu T, Uchigashima M, Konno K, Yamanaka A, Kobayashi K, Watanabe M, Koyama Y, Sakurai T. Chronic alterations in monoaminergic cells in the locus coeruleus in orexin neuron-ablated narcoleptic mice. PLoS One, 2013; 8: e70012.
    3. John J, Thannickal TC, McGregor R, Ramanathan L, Ohtsu H, Nishino S, Sakai N, Yamanaka A, Stone C, Cornford M, Siegel JM. Greatly increased numbers of histamine cells in human narcolepsy with cataplexy. Ann Neurol, 2013; 74: 786-793.
    4. Taguchi T, Yasui M, Kubo A, Abe M, Kiyama H, Yamanaka A, Mizumura K. Nociception originating from the crural fascia in rats. Pain, 2013; 154: 1103-1114.
    5. Tsunematsu T, Tabuchi S, Tanaka KF, Boyden ES, Tominaga M, Yamanaka A. Long-lasting silencing of orexin/hypocretin neurons using archaerhodopsin induces slow-wave sleep in mice. Behav Brain Res, 2013; 255: 64-74.
    6. Inutsuka A, Yamanaka A. The regulation of sleep and wakefulness by the hypothalamic neuropeptide orexin/hypocretin. Nagoya J Med Sci, 2013; 75: 29-36.
    7. Inutsuka A, Yamanaka A. The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions. Front Endocrinol (Lausanne), 2013; 4: 18.
    8. Koizumi A, Tanaka KF, Yamanaka A. The manipulation of neural and cellular activities by ectopic expression of melanopsin. Neurosci Res, 2013; 75: 3-5.
    9. Tsunematsu T, Tanaka KF, Yamanaka A, Koizumi A. Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of wakefulness of mice in vivo by blue light. Neurosci Res, 2013; 75: 23-28.
    10. Imayoshi I, Tabuchi S, Hirano K, Sakamoto M, Kitano S, Miyachi H, Yamanaka A, Kageyama R. Light-induced silencing of neural activity in Rosa26 knock-in mice conditionally expressing the microbial halorhodopsin eNpHR2.0. Neurosci Res, 2013; 75: 53-58.
    11. Yamashita T, Pala A, Pedrido L, Kremer Y, Welker E, Petersen CCH. Membrane potential dynamics of neocortical projection neurons driving target-specific signals. Neuron, 2013; 80: 1477-1490.
    12. Ono D, Honma S, Honma K. Postnatal constant light compensates Cryptochrome1 and 2 double deficiency for disruption of circadian behavioral rhythms in mice under constant dark. PLoS One, 2013; 8: e80615.
    13. Ono D, Honma S, Honma K. Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus. Nat Commun, 2013; 4: 1666.
  • 2012年
    1. Tanaka KF, Matsui K, Sasaki T, Sano H, Sugio S, Fan K, Hen R, Nakai J, Yanagawa Y, Hasuwa H, Okabe M, Deisseroth K, Ikenaka K, Yamanaka A. Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. Cell Rep, 2012; 2: 397-406.
    2. Yamashita T. Ca2+-dependent regulation of synaptic vesicle endocytosis. Neurosci Res, 2012; 73: 1-7.
    3. Enoki R, Kuroda S, Ono D, Hasan MT, Ueda T, Honma S, Honma K. Topological specificity and hierarchical network of the circadian calcium rhythm in the suprachiasmatic nucleus. Proc Natl Acad Sci U S A, 2012; 109: 21498-21503.
    4. Yoshitane H, Honma S, Imamura K, Nakajima H, Nishide SY, Ono D, Kiyota H, Shinozaki N, Matsuki H, Wada N, Doi H, Hamada T, Honma K, Fukada Y. JNK regulates the photic response of the mammalian circadian clock. EMBO Rep, 2012; 13: 455-461.
  • 2011年
    1. Tsunematsu T, Kilduff TS, Boyden ES, Takahashi S, Tominaga M, Yamanaka A. Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J Neurosci, 2011; 31: 10529-10539.
    2. Hirashima N, Tsunematsu T, Ichiki K, Tanaka H, Kilduff TS, Yamanaka A. Neuropeptide B induces slow wave sleep in mice. Sleep, 2011; 34: 31-37.
  • 2010年
    1. Yamanaka A, Tabuchi S, Tsunematsu T, Fukazawa Y, Tominaga M. Orexin directly excites orexin neurons through orexin 2 receptor. J Neurosci, 2010; 30: 12642-12652.
    2. Mihara H, Boudaka A, Shibasaki K, Yamanaka A, Sugiyama T, Tominaga M. Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice. J Neurosci, 2010; 30: 16536-16544.
    3. Kawaguchi H, Yamanaka A, Uchida K, Shibasaki K, Sokabe T, Maruyama Y, Yanagawa Y, Murakami S, Tominaga M. Activation of polycystic kidney disease-2-like 1 (PKD2L1)-PKD1L3 complex by acid in mouse taste cells. J Biol Chem, 2010; 285: 17277-17281.
    4. Yamashita T, Eguchi K, Saitoh N, von Gersdorff H, Takahashi T. Developmental shift to a mechanism of synaptic vesicle endocytosis requiring nanodomain Ca2+. Nat Neurosci, 2010; 13: 838-844.
    5. Watanabe H, Yamashita T, Saitoh N, Kiyonaka S, Iwamatsu A, Campbell KP, Mori Y, Takahashi T. Involvement of Ca2+ channel synprint site in synaptic vesicle endocytosis. J Neurosci, 2010; 30: 655-660.
  • 2009年
    1. Yamashita T, Kanda T, Eguchi K, Takahashi T. Vesicular glutamate filling and AMPA receptor occupancy at the calyx of Held synapse of immature rats. J Physiol, 2009; 587: 2327-2339.
  • 2008年
    1. Tsunematsu T, Fu LY, Yamanaka A, Ichiki K, Tanoue A, Sakurai T, van den Pol AN. Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: implications for water homeostasis. J Neurosci, 2008; 28: 228-238.
    2. Xie X, Wisor JP, Hara J, Crowder TL, LeWinter R, Khroyan TV, Yamanaka A, Diano S, Horvath TL, Sakurai T, Toll L, Kilduff TS. Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. J Clin Invest, 2008; 118: 2471-2481.
    3. Nakamura T, Yamashita T, Saitoh N, Takahashi T. Developmental changes in calcium/calmodulin-dependent inactivation of calcium currents at the rat calyx of Held. J Physiol, 2008; 586: 2253-2261.
    4. Koike-Tani M, Kanda T, Saitoh N, Yamashita T, Takahashi T. Involvement of AMPA receptor desensitization in short-term synaptic depression at the calyx of Held in developing rats. J Physiol, 2008; 586: 2263-2275.
  • 2006年
    1. Obara K, Uchino M, Koide M, Yamanaka A, Nakayama K. Stretch-induced triphosphorylation of myosin light chain and myogenic tone in canine basilar artery. Eur J Pharmacol, 2006; 534: 141-151.
    2. Takayasu S, Sakurai T, Iwasaki S, Teranishi H, Yamanaka A, Williams SC, Iguchi H, Kawasawa YI, Ikeda Y, Sakakibara I, Ohno K, Ioka RX, Murakami S, Dohmae N, Xie J, Suda T, Motoike T, Ohuchi T, Yanagisawa M, Sakai J. A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice. Proc Natl Acad Sci U S A, 2006; 103: 7438-7443.
    3. Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K, Nakazato M. Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology, 2006; 147: 2306-2314.
    4. Yamanaka A, Muraki Y, Ichiki K, Tsujino N, Kilduff TS, Goto K, Sakurai T. Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner. J Neurophysiol, 2006; 96: 284-298.
    5. Xie X, Crowder TL, Yamanaka A, Morairty SR, Lewinter RD, Sakurai T, Kilduff TS. GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus. J Physiol, 2006; 574: 399-414.
  • 2005年
    1. Sakurai T, Nagata R, Yamanaka A, Kawamura H, Tsujino N, Muraki Y, Kageyama H, Kunita S, Takahashi S, Goto K, Koyama Y, Shioda S, Yanagisawa M. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron, 2005; 46: 297-308.
    2. Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff TS, Yagami K, Takahashi S, Goto K, Sakurai T. Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor. J Neurosci, 2005; 25: 7459-7469.
    3. Yamashita T, Hige T, Takahashi T. Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse. Science, 2005; 307: 124-127.
  • 2004年
    1. Muroya S, Funahashi H, Yamanaka A, Kohno D, Uramura K, Nambu T, Shibahara M, Kuramochi M, Takigawa M, Yanagisawa M, Sakurai T, Shioda S, Yada T. Orexins (hypocretins) directly interact with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca 2+ signaling in a reciprocal manner to leptin: orexigenic neuronal pathways in the mediobasal hypothalamus. Eur J Neurosci, 2004; 19: 1524-1534.
    2. Muraki Y, Yamanaka A, Tsujino N, Kilduff TS, Goto K, Sakurai T. Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor. J Neurosci, 2004; 24: 7159-7166.
    3. Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T, Kilduff TS, Horvath TL, de Lecea L. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci, 2004; 24: 11439-11448.
  • 2003年
    1. Yamanaka A, Muraki Y, Tsujino N, Goto K, Sakurai T. Regulation of orexin neurons by the monoaminergic and cholinergic systems. Biochem Biophys Res Commun, 2003; 303: 120-129.
    2. Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N, Garry MG, Lerner MR, King DS, O'Dowd BF, Sakurai T, Yanagisawa M. Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Proc Natl Acad Sci U S A, 2003; 100: 6251-6256.
    3. Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron, 2003; 38: 701-713.
    4. Zhu Y, Miwa Y, Yamanaka A, Yada T, Shibahara M, Abe Y, Sakurai T, Goto K. Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. J Pharmacol Sci, 2003; 92: 259-266.
    5. Yamashita T, Ishikawa T, Takahashi T. Developmental increase in vesicular glutamate content does not cause saturation of AMPA receptors at the calyx of Held synapse. J Neurosci, 2003; 23: 3633-3638.
  • 2002年
    1. Yamanaka A, Tsujino N, Funahashi H, Honda K, Guan JL, Wang QP, Tominaga M, Goto K, Shioda S, Sakurai T. Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem Biophys Res Commun, 2002; 290: 1237-1245.
    2. Nanmoku T, Isobe K, Sakurai T, Yamanaka A, Takekoshi K, Kawakami Y, Goto K, Nakai T. Effects of orexin on cultured porcine adrenal medullary and cortex cells. Regul Pept, 2002; 104: 125-130.
    3. Zhu Y, Yamanaka A, Kunii K, Tsujino N, Goto K, Sakurai T. Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways. Physiol Behav, 2002; 77: 251-257.
    4. Miyakawa N, Uchino S, Yamashita T, Okada H, Nakamura T, Kaminogawa S, Miyamoto Y, Hisatsune T. A glycine receptor antagonist, strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex. Neuroreport, 2002; 13: 1667-1673.
  • 2001年
    1. Yamada M, Miyakawa T, Duttaroy A, Yamanaka A, Moriguchi T, Makita R, Ogawa M, Chou CJ, Xia B, Crawley JN, Felder CC, Deng CX, Wess J. Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature, 2001; 410: 207-212.
    2. Obara K, Saito M, Yamanaka A, Uchino M, Nakayama K. Involvement of different activator Ca(2+) in the rate-dependent stretch-induced contractions of canine basilar artery. Jpn J Physiol, 2001; 51: 327-335.
  • 2000年
    1. Yamanaka A, Kunii K, Nambu T, Tsujino N, Sakai A, Matsuzaki I, Miwa Y, Goto K, Sakurai T. Orexin-induced food intake involves neuropeptide Y pathway. Brain Res, 2000; 859: 404-409.
    2. Abe Y, Nakayama K, Yamanaka A, Sakurai T, Goto K. Subtype-specific trafficking of endothelin receptors. J Biol Chem, 2000; 275: 8664-8671.
    3. Nanmoku T, Isobe K, Sakurai T, Yamanaka A, Takekoshi K, Kawakami Y, Ishii K, Goto K, Nakai T. Orexins suppress catecholamine synthesis and secretion in cultured PC12 cells. Biochem Biophys Res Commun, 2000; 274: 310-315.
  • 1999年
    1. Kunii K, Yamanaka A, Nambu T, Matsuzaki I, Goto K, Sakurai T. Orexins/hypocretins regulate drinking behaviour. Brain Res, 1999; 842: 256-261.
    2. Yamanaka A, Sakurai T, Katsumoto T, Yanagisawa M, Goto K. Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight. Brain Res, 1999; 849: 248-252.
  • 1998年
    1. Yamanaka A, Ishikawa T, Goto K. Characterization of endothelium-dependent relaxation independent of NO and prostaglandins in guinea pig coronary artery. J Pharmacol Exp Ther, 1998; 285: 480-489.
  • 1997年
    1. Yamada M, Ishikawa T, Yamanaka A, Fujimori A, Goto K. Local neurogenic regulation of rat hindlimb circulation: CO2-induced release of calcitonin gene-related peptide from sensory nerves. Br J Pharmacol, 1997; 122: 710-714.

研究キーワード

視床下部、オレキシン、本能行動、睡眠・覚醒、概日リズム、光遺伝学、薬理遺伝学、大脳皮質、パッチクランプ、学習・記憶

博士研究員・大学院生募集

熱意ある博士研究員および大学院生(修士、博士課程)を募集しています。

問い合わせ先

山中 章弘 教授 
e-mail: yamank@riem.nagoya-u.ac.jp