Gene Symbol: hcrt
Description: hypocretin (orexin) neuropeptide precursor
Alias: orexin, hypocretin/orexin
Species: zebrafish

Top Publications

  1. Prober D, Rihel J, Onah A, Sung R, Schier A. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006;26:13400-10 pubmed
    ..The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, ..
  2. Blechman J, Borodovsky N, Eisenberg M, Nabel Rosen H, Grimm J, Levkowitz G. Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia. Development. 2007;134:4417-26 pubmed
    ..Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates, and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation. ..
  3. Woods I, Schoppik D, Shi V, Zimmerman S, Coleman H, Greenwood J, et al. Neuropeptidergic signaling partitions arousal behaviors in zebrafish. J Neurosci. 2014;34:3142-60 pubmed publisher
  4. Madelaine R, Lovett Barron M, Halluin C, Andalman A, Liang J, Skariah G, et al. The hypothalamic NPVF circuit modulates ventral raphe activity during nociception. Sci Rep. 2017;7:41528 pubmed publisher
    ..This study reveals a novel NPVF-vRN functional circuit modulated by noxious stimuli in vertebrates. ..
  5. Pavlidis M, Sundvik M, Chen Y, Panula P. Adaptive changes in zebrafish brain in dominant-subordinate behavioral context. Behav Brain Res. 2011;225:529-37 pubmed publisher
    ..of histamine (histidine decarboxylase, HDC) and in the general stress response (galanin, GAL; hypocretin/orexin, Hcrt) was examined. The MR/GR ratio was higher in dominant and subordinate fish than in controls (P=0.016)...
  6. Kurrasch D, Nevin L, Wong J, Baier H, Ingraham H. Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish. Neural Dev. 2009;4:22 pubmed publisher
    ..Based on our collective findings, we speculate that neuroendocrine transcriptional programs adapt dynamically to both the supply and demand for neuropeptides to ensure adequate homeostatic responses. ..
  7. Chen A, Singh C, Oikonomou G, Prober D. Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep. Eneuro. 2017;4: pubmed publisher
    ..with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants...
  8. Naumann E, Kampff A, Prober D, Schier A, Engert F. Monitoring neural activity with bioluminescence during natural behavior. Nat Neurosci. 2010;13:513-20 pubmed publisher
    ..Our neuroluminescence assay can report, with high temporal resolution and sensitivity, the activity of small subsets of neurons during unrestrained behavior. ..
  9. Choi H, Calvert C, Husain N, Huss D, Barsi J, Deverman B, et al. Mapping a multiplexed zoo of mRNA expression. Development. 2016;143:3632-3637 pubmed

More Information


  1. Sterling M, Chang G, Karatayev O, Chang S, Leibowitz S. Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides. Behav Brain Res. 2016;304:125-38 pubmed publisher
    ..hypothalamic neurogenesis and the proliferation and expression of the orexigenic peptides, galanin (GAL) and orexin (OX), in the anterior hypothalamus...
  2. Kaslin J, Nystedt J, Ostergård M, Peitsaro N, Panula P. The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J Neurosci. 2004;24:2678-89 pubmed
    The orexin/hypocretin (ORX) system is involved in physiological processes such as feeding, energy metabolism, and the control of sleep and wakefulness...
  3. Li X, Zhang Y, Li X, Feng D, Zhang S, Zhao X, et al. Comparative analysis of biological effect of corannulene and graphene on developmental and sleep/wake profile of zebrafish larvae. Acta Biomater. 2017;55:271-282 pubmed publisher
    ..Finally, the effect of corannulene or graphene on the hypocretin (hcrt) system and sleep/wake regulators such as hcrt, hcrt G-protein coupled receptor (hcrtr), and arylalkylamine N-..
  4. Sterling M, Karatayev O, Chang G, Algava D, Leibowitz S. Model of voluntary ethanol intake in zebrafish: effect on behavior and hypothalamic orexigenic peptides. Behav Brain Res. 2015;278:29-39 pubmed publisher
    ..ethanol intake on different behaviors and the expression of hypothalamic orexigenic peptides, galanin (GAL) and orexin (OX), which are known in rodents to stimulate consumption of ethanol and alter behaviors associated with alcohol ..
  5. Theodoridi A, Tsalafouta A, Pavlidis M. Acute Exposure to Fluoxetine Alters Aggressive Behavior of Zebrafish and Expression of Genes Involved in Serotonergic System Regulation. Front Neurosci. 2017;11:223 pubmed publisher
    ..Overall, an acute administration of a selective serotonin reuptake inhibitor alters aggressive behavior in male zebrafish in association with changes in the neuroendocrine mediators of coping styles. ..
  6. Chen H, Huang H, Chen X, Deng S, Zhu C, Huang H, et al. Structural and functional characterization of neuromedin S in the teleost fish, zebrafish (Danio rerio). Comp Biochem Physiol B Biochem Mol Biol. 2016;191:76-83 pubmed publisher
    ..of zebrafish NMSRP by intraperitoneal injection significantly promoted the expression of neuropeptide Y (NPY) and orexin, suggesting an orexigenic role for NMSRP in zebrafish...
  7. Dalmolin C, Almeida D, Figueiredo M, Marins L. Food intake and appetite control in a GH-transgenic zebrafish. Fish Physiol Biochem. 2015;41:1131-41 pubmed publisher
    ..It is clear that transgenic zebrafish eat more and faster, and it seems that it occurs due to pomc down-regulation, since npy might be under regulation of the humoral factor glucose. ..
  8. Chen S, Reichert S, Singh C, Oikonomou G, Rihel J, Prober D. Light-Dependent Regulation of Sleep and Wake States by Prokineticin 2 in Zebrafish. Neuron. 2017;95:153-168.e6 pubmed publisher
    ..These results suggest that Prok2 antagonizes the direct wake-promoting effect of light in zebrafish, in part through the induction of galn expression in the hypothalamus. ..
  9. Russek Blum N, Gutnick A, Nabel Rosen H, Blechman J, Staudt N, Dorsky R, et al. Dopaminergic neuronal cluster size is determined during early forebrain patterning. Development. 2008;135:3401-13 pubmed publisher
    ..This study also shows, for the first time, that diencephalic DA population size is modulated inside the neural plate much earlier than expected, concomitant with Wnt-mediated regional patterning events. ..
  10. Holden T, Nguyen A, Lin E, Cheung E, Dehipawala S, Ye J, et al. Exploratory bioinformatics study of lncRNAs in Alzheimer's disease mRNA sequences with application to drug development. Comput Math Methods Med. 2013;2013:579136 pubmed publisher
    ..inclusion of erythropoietin (where all CDSs have higher FD than mRNA) would suppress correlation, suggesting that HCRT, a hypothalamus neurotransmitter related to the wake/sleep cycle, might be better when compared to EPO, a ..
  11. Novak C, Jiang X, Wang C, Teske J, Kotz C, Levine J. Caloric restriction and physical activity in zebrafish (Danio rerio). Neurosci Lett. 2005;383:99-104 pubmed
    ..No change in orexin mRNA was seen after 2 days of food deprivation...
  12. Liu J, Merkle F, Gandhi A, Gagnon J, Woods I, Chiu C, et al. Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9. Development. 2015;142:1113-24 pubmed publisher
    Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy...
  13. Chen Y, Sundvik M, Rozov S, Priyadarshini M, Panula P. MANF regulates dopaminergic neuron development in larval zebrafish. Dev Biol. 2012;370:237-49 pubmed publisher
    ..Strikingly, manf mRNA could partly restore the decrease of th1 positive cells in Nr4a2-deficient larvae. These results suggest that MANF is involved in the regulation of the development of dopaminergic system in zebrafish. ..
  14. Podlasz P, Sallinen V, Chen Y, Kudo H, Fedorowska N, Panula P. Galanin gene expression and effects of its knock-down on the development of the nervous system in larval zebrafish. J Comp Neurol. 2012;520:3846-62 pubmed publisher
    ..not alter the expression of tyrosine hydroxylases 1 and 2, choline acetyltransferase, histidine decarboxylase, or orexin mRNA...
  15. Singh C, Oikonomou G, Prober D. Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish. elife. 2015;4:e07000 pubmed publisher
    ..Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal...
  16. Yelin Bekerman L, Elbaz I, Diber A, Dahary D, Gibbs Bar L, Alon S, et al. Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a. elife. 2015;4:e08638 pubmed publisher
    ..The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\wake states, feeding, stress, and reward...
  17. Pavlidis M, Theodoridi A, Tsalafouta A. Neuroendocrine regulation of the stress response in adult zebrafish, Danio rerio. Prog Neuropsychopharmacol Biol Psychiatry. 2015;60:121-31 pubmed publisher
    ..factor, crf; pro-opiomelanocortin, pomc; glucocorticoid receptor, gr; MR/GR ratio; prolactin, prl; hypocretin/orexin, hcrt; brain-derived neurotrophic factor, bdnf; c-fos)...
  18. Schweitzer J, Löhr H, Bonkowsky J, Hübscher K, Driever W. Sim1a and Arnt2 contribute to hypothalamo-spinal axon guidance by regulating Robo2 activity via a Robo3-dependent mechanism. Development. 2013;140:93-106 pubmed publisher
    ..Therefore, Sim1a and Arnt2 contribute to control of lateral positioning of longitudinal hypothalamic-spinal axons by negative regulation of robo3a.1 expression, which in turn attenuates the repulsive activity of Robo2. ..
  19. Faraco J, Appelbaum L, Marin W, Gaus S, Mourrain P, Mignot E. Regulation of hypocretin (orexin) expression in embryonic zebrafish. J Biol Chem. 2006;281:29753-61 pubmed
    ..A critical region of 250 base pairs was identified containing a core 13-base pair element essential for hypocretin expression. ..
  20. Elbaz I, Yelin Bekerman L, Nicenboim J, Vatine G, Appelbaum L. Genetic ablation of hypocretin neurons alters behavioral state transitions in zebrafish. J Neurosci. 2012;32:12961-72 pubmed publisher
    ..Narcolepsy is caused by selective degeneration of hypothalamic hypocretin/orexin (HCRT) neurons...
  21. Appelbaum L, Wang G, Maro G, Mori R, Tovin A, Marin W, et al. Sleep-wake regulation and hypocretin-melatonin interaction in zebrafish. Proc Natl Acad Sci U S A. 2009;106:21942-7 pubmed publisher
    In mammals, hypocretin/orexin (HCRT) neuropeptides are important sleep-wake regulators and HCRT deficiency causes narcolepsy...
  22. Elbaz I, Zada D, Tovin A, Braun T, Lerer Goldshtein T, Wang G, et al. Sleep-Dependent Structural Synaptic Plasticity of Inhibitory Synapses in the Dendrites of Hypocretin/Orexin Neurons. Mol Neurobiol. 2017;54:6581-6597 pubmed publisher
    ..The hypothalamic hypocretin/orexin (Hcrt) neurons regulate various functions including feeding, reward, sleep, and wake...
  23. Appelbaum L, Wang G, Yokogawa T, Skariah G, Smith S, Mourrain P, et al. Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron. 2010;68:87-98 pubmed publisher
    ..zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night...
  24. Chen Y, Semenova S, Rozov S, Sundvik M, Bonkowsky J, Panula P. A Novel Developmental Role for Dopaminergic Signaling to Specify Hypothalamic Neurotransmitter Identity. J Biol Chem. 2016;291:21880-21892 pubmed
    Hypothalamic neurons expressing histamine and orexin/hypocretin (hcrt) are necessary for normal regulation of wakefulness...
  25. Zhao Y, Singh C, Prober D, Wayne N. Morphological and Physiological Interactions Between GnRH3 and Hypocretin/Orexin Neuronal Systems in Zebrafish (Danio rerio). Endocrinology. 2016;157:4012-4020 pubmed
    ..Hypocretin (Hcrt) (also known as orexin) is one such peptide, primarily controlling sleep/wakefulness, food intake, and reward processing...
  26. Sundvik M, Kudo H, Toivonen P, Rozov S, Chen Y, Panula P. The histaminergic system regulates wakefulness and orexin/hypocretin neuron development via histamine receptor H1 in zebrafish. FASEB J. 2011;25:4338-47 pubmed publisher
    The histaminergic and hypocretin/orexin (hcrt) neurotransmitter systems play crucial roles in alertness/wakefulness in rodents...
  27. Pauli A, Montague T, Lennox K, Behlke M, Schier A. Antisense Oligonucleotide-Mediated Transcript Knockdown in Zebrafish. PLoS ONE. 2015;10:e0139504 pubmed publisher
    ..Despite this drawback, quantitation of knockdown efficiency and the ability to degrade lncRNAs make ASOs a useful knockdown reagent in zebrafish. ..
  28. Levitas Djerbi T, Yelin Bekerman L, Lerer Goldshtein T, Appelbaum L. Hypothalamic leptin-neurotensin-hypocretin neuronal networks in zebrafish. J Comp Neurol. 2015;523:831-48 pubmed publisher
    ..In mammals, NTS-producing neurons that express leptin receptor (LepRb) regulate the function of hypocretin/orexin (HCRT) and dopamine neurons...
  29. Nishimura Y, Okabe S, Sasagawa S, Murakami S, Ashikawa Y, Yuge M, et al. Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers. Front Pharmacol. 2015;6:257 pubmed publisher
    ..We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants...
  30. Appelbaum L, Skariah G, Mourrain P, Mignot E. Comparative expression of p2x receptors and ecto-nucleoside triphosphate diphosphohydrolase 3 in hypocretin and sensory neurons in zebrafish. Brain Res. 2007;1174:66-75 pubmed
    The hypocretin/orexin (HCRT/ORX) excitatory neuropeptides are expressed in a small population of lateral hypothalamic cells in mammals and fish. In humans, loss of these cells causes the sleep disorder narcolepsy...
  31. Yokobori E, Kojima K, Azuma M, Kang K, Maejima S, Uchiyama M, et al. Stimulatory effect of intracerebroventricular administration of orexin A on food intake in the zebrafish, Danio rerio. Peptides. 2011;32:1357-62 pubmed publisher
    b>Orexin is a potent orexigenic neuropeptide implicated in feeding regulation of mammals. However, except for the case of goldfish, the involvement of orexin in the feeding behavior of teleost fish has not well been studied...