Regulation of Organ Function(Cooperating field)Neural Regulation


We investigate the neuronal basis of animal behavior and neurological disorder, using model animals such as mice. We are particularly interested in functions of hypothalamic peptidergic neurons and their associated neuronal circuits that control instinctive behaviors (feeding, sleep/wakefulness, sexual behavior) and adaptive behaviors (learning, social behavior). Using recent techniques called optogenetics and pharmacogenetics combined with other conventional techniques, we study causal roles of specific types of neurons or specific neuronal pathways in animal behavior at the levels of molecule, synapse, cell and network.

Research Projects

1) Neuronal basis of instinctive behaviors

Hypothalamic peptiderdic neurons have a pivotal role in the regulation of instinctive behaviors such as sleeping. We have studied orexin/hypocretin neurons in the lateral hypothalamus and identified their pre- and postsynaptic networks as well as humoral factors that affect their activities. Recently, we have revealed the causal role of orexin/hypocretin neurons in sleep-wake regulation, using optogenetics and pharmacogenetics, cell-type-specific ablation. Currently we continue these studies and we are also focusing other neuronal populations such as hypothalamic MCH (melanin-containing hormone) neurons and their pre- and postsynaptic neurons.

Representative publications:
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) Neuronal basis of sentience

Primary sensory cortex is the key brain structure for animals to create their "sentience" that is the capacity to feel, perceive, or experience subjectively. We have investigated information processing by primary sensory cortex and its plasticity upon learning, and discovered the projection-specific nature of cortical sensory processing (Yamashita et al., Neuron, 2013; Yamashita and Petersen, eLife, 2016). We are further studying how cortical sensory processing is organized in projection-specific ways. Please refer to our group webpage for details:

Representative publications:
eLife 5, e15798 (2016); Neuron 80, 1477-1490 (2013); Nature Neuroscience 13, 838-844 (2010); Science 307, 124-127 (2005)

3) Development of novel optogenetical methods

Opsins used for current optogenetics can be activated by radiation of visible light such as red, blue and green. As visible light does not penetrate through thick mammalian tissue, it is impossible to activate neurons in deep brain without insertion of an optic fiber. We are collaborating with many laboratories to create a novel methodology which enables us to manipulate neuronal activities in deep brain from outside of the body without insertion of an optic fiber. (Funding: CREST to Akihiro Yamanaka; PRESTO to Takayuki Yamashita)

Faculty Members

YAMANAKA, Akihiro Professor Department of Neuroscience, Division of Stress Recognition and Response, Research Institute of Environmental Medicine (Higashiyama Campus)
ONO, Daisuke Assistant Professor Department of Neuroscience, Division of Stress Recognition and Response, Research Institute of Environmental Medicine (Higashiyama Campus)
YAMAGUCHI, Hiroshi Designated Assistant Professor Department of Neuroscience, Division of Stress Recognition and Response, Research Institute of Environmental Medicine (Higashiyama Campus)


  • 2020
    1. 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 (2020 in press)
    2. Wang HY, Eguchi K, Yamashita T, Takahashi T: Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. J Neurosci (2020 in press)
    3. Ohmura Y, Tsutsui-Kimura I, Sasamori H, Nebuka M, Nishitani N, Tanaka KF, Yamanaka A, Yoshioka M. Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects. Neuropharmacology, 2020; 167: 107703.
    4. 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, 2020; 13: 14.
    5. 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 alpha1 adrenoceptors in the medial prefrontal cortex of mice. Neuropharmacology, 2020; 166: 107968.
    6. 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, 2020; 10: 3191.
    7. Nebuka M, Ohmura Y, Izawa S, Bouchekioua Y, Nishitani N, Yoshida T, Yoshioka M. Behavioral characteristics of 5-HT2C receptor knockout mice: Locomotor activity, anxiety-, and fear memory-related behaviors. Behav Brain Res, 2020; 379: 112394.
    8. Hung CJ, Ono D, Kilduff TS, Yamanaka A. Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy. Elife, 2020; 9.
    9. 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, 2020; 13: 60.
    10. 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. Communications Biology, 2020; 3: 227.
    11. 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. Nature Neuroscience, 2020; 23: 638-650.
  • 2019
    1. 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 Biol, 2019.
    2. Miyazaki T, Chowdhury S, Yamashita T, Matsubara T, Yawo H, Yuasa H, Yamanaka A. Large Timescale Interrogation of Neuronal Function by Fiberless Optogenetics Using Lanthanide Micro-particles. Cell Rep, 2019; 26: 1033-1043.e1035.
    3. 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.
    4. 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.
    5. Macpherson T, Mizoguchi H, Yamanaka A, Hikida T. Preproenkephalin-expressing ventral pallidal neurons control inhibitory avoidance learning. Neurochem Int, 2019; 126: 11-18.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
    14. 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.
    15. 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.
    16. 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.
  • 2018
    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
    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. Hayasaka N, Hirano A, Miyoshi Y, Tokuda IT, Yoshitane H, Matsuda J, Fukada Y. Salt-inducible kinase 3 regulates the mammalian circadian clock by destabilizing PER2 protein. Elife, 2017; 6.
    10. 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
    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.
    8. Miyamoto D, Hirai D, Fung CC, Inutsuka A, Odagawa M, Suzuki T, Boehringer R, Adaikkan C, Matsubara C, Matsuki N, Fukai T, McHugh TJ, Yamanaka A, Murayama M. Top-down cortical input during NREM sleep consolidates perceptual memory. Science, 2016; 352: 1315-1318.
    9. Wakaizumi K, Kondo T, Hamada Y, Narita M, Kawabe R, Narita H, Watanabe M, Kato S, Senba E, Kobayashi K, Kuzumaki N, Yamanaka A, Morisaki H, Narita M. Involvement of mesolimbic dopaminergic network in neuropathic pain relief by treadmill exercise: A study for specific neural control with Gi-DREADD in mice. Mol Pain, 2016; 12.
    10. Mizumura K, Taguchi T. Delayed onset muscle soreness: Involvement of neurotrophic factors. J Physiol Sci, 2016; 66: 43-52.
  • 2015
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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.

Research Keywords

Hypothalamus、 Orexin、 Sleep and wake、 Instinctive behavior、 Circadian rhythm、 Optogenetics、 Pharmacogenetics、 Cerebral cortex、 Patch-clamp、 Learning and memory

Call for post-docs and graduate students

We are currently seeking post-doctoral researchers and graduate students who are interested in our projects and highly motivated to lead a research program in a team environment.

For detailed information, please do not hesitate to contact us.

Professor Akihiro Yamanaka

Tel +81-52-789-3864