Advertisement

The Hypocretin/Orexin Neuronal Networks in Zebrafish

  • Idan Elbaz
  • Talia Levitas-Djerbi
  • Lior Appelbaum
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 33)

Abstract

The hypothalamic Hypocretin/Orexin (Hcrt) neurons secrete two Hcrt neuropeptides. These neurons and peptides play a major role in the regulation of feeding, sleep wake cycle, reward-seeking, addiction, and stress. Loss of Hcrt neurons causes the sleep disorder narcolepsy. The zebrafish has become an attractive model to study the Hcrt neuronal network because it is a transparent vertebrate that enables simple genetic manipulation, imaging of the structure and function of neuronal circuits in live animals, and high-throughput monitoring of behavioral performance during both day and night. The zebrafish Hcrt network comprises ~16–60 neurons, which similar to mammals, are located in the hypothalamus and widely innervate the brain and spinal cord, and regulate various fundamental behaviors such as feeding, sleep, and wakefulness. Here we review how the zebrafish contributes to the study of the Hcrt neuronal system molecularly, anatomically, physiologically, and pathologically.

Keywords

Behavior Hypocretin Narcolepsy Orexin Sleep Zebrafish 

Notes

Acknowledgments

This work was supported by the Israel Science Foundation (grant no. 690/15), the Legacy Heritage Biomedical Program of the Israel Science Foundation (grant no. 992/14), and by the US-Israel Binational Science Foundation (BSF, grant no. 2011335). IE is supported by the Nehemia Levtzion scholarship from the Council for Higher Education, Israel.

References

  1. 1.
    Burt J, Alberto CO, Parsons MP, Hirasawa M (2011) Local network regulation of orexin neurons in the lateral hypothalamus. Am J Physiol Regul Integr Comp Physiol 301:R572–R580PubMedGoogle Scholar
  2. 2.
    DiLeone RJ, Georgescu D, Nestler EJ (2003) Lateral hypothalamic neuropeptides in reward and drug addiction. Life Sci 73:759–768PubMedGoogle Scholar
  3. 3.
    Saper CB (2006) Staying awake for dinner: hypothalamic integration of sleep, feeding, and circadian rhythms. Prog Brain Res 153:243–252PubMedGoogle Scholar
  4. 4.
    Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257–1263PubMedGoogle Scholar
  5. 5.
    de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, et al. (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A 95:322–327PubMedPubMedCentralGoogle Scholar
  6. 6.
    Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, et al. (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585PubMedGoogle Scholar
  7. 7.
    Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, et al. (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451Google Scholar
  8. 8.
    Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa M, Nakazato M (1999) Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci U S A 96:748–753PubMedPubMedCentralGoogle Scholar
  9. 9.
    Elias CF, Saper CB, Maratos-Flier E, Tritos NA, Lee C, Kelly J, Tatro JB, Hoffman GE, Ollmann MM, Barsh GS, et al. (1998) Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 402:442–459PubMedGoogle Scholar
  10. 10.
    Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K (1999) Distribution of orexin neurons in the adult rat brain. Brain Res 827:243–260PubMedGoogle Scholar
  11. 11.
    Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015PubMedGoogle Scholar
  12. 12.
    Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM (2000) Reduced number of hypocretin neurons in human narcolepsy. Neuron 27:469–474Google Scholar
  13. 13.
    Sakurai T (2014) The role of orexin in motivated behaviours. Nat Rev Neurosci 15:719–731Google Scholar
  14. 14.
    Tabuchi S, Tsunematsu T, Black SW, Tominaga M, Maruyama M, Takagi K, Minokoshi Y, Sakurai T, Kilduff TS, Yamanaka A (2014) Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J Neurosci 34:6495–6509PubMedPubMedCentralGoogle Scholar
  15. 15.
    Wong KKY, Ng SYL, Lee LTO, Ng HKH, Chow BKC (2011) Orexins and their receptors from fish to mammals: a comparative approach. Gen Comp Endocrinol 171:124–130PubMedGoogle Scholar
  16. 16.
    Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, et al. (2001) Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30:345–354PubMedGoogle Scholar
  17. 17.
    Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98:365–376Google Scholar
  18. 18.
    Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE (2004) Behavioral state instability in orexin knock-out mice. J Neurosci 24:6291–6300PubMedGoogle Scholar
  19. 19.
    Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, et al. (2000) A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6:991–997PubMedGoogle Scholar
  20. 20.
    Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000) Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355:39–40Google Scholar
  21. 21.
    Fernandes AM, Fero K, Driever W, Burgess HA (2013) Enlightening the brain: linking deep brain photoreception with behavior and physiology. Bioessays 35:775–779PubMedPubMedCentralGoogle Scholar
  22. 22.
    Varshney GK, Burgess SM (2014) Mutagenesis and phenotyping resources in zebrafish for studying development and human disease. Brief Funct Genomics 13:82–94PubMedGoogle Scholar
  23. 23.
    Wang G, Grone B, Colas D, Appelbaum L, Mourrain P (2011) Synaptic plasticity in sleep: learning, homeostasis and disease. Trends Neurosci 34:452–463PubMedPubMedCentralGoogle Scholar
  24. 24.
    Wolman M, Granato M (2012) Behavioral genetics in larval zebrafish: learning from the young. Dev Neurobiol 72:366–372PubMedGoogle Scholar
  25. 25.
    Leung LC, Wang GX, Mourrain P (2013) Imaging zebrafish neural circuitry from whole brain to synapse. Front Neural Circuits 7:76PubMedPubMedCentralGoogle Scholar
  26. 26.
    Maximino C, de Brito TM, da Silva Batista AW, Herculano AM, Morato S, Gouveia A (2010) Measuring anxiety in zebrafish: a critical review. Behav Brain Res 214:157–171PubMedGoogle Scholar
  27. 27.
    Norton W, Bally-Cuif L (2010) Adult zebrafish as a model organism for behavioural genetics. BMC Neurosci 11:90PubMedPubMedCentralGoogle Scholar
  28. 28.
    Kawakami K (2007) Tol2: a versatile gene transfer vector in vertebrates. Genome Biol 8:S7PubMedPubMedCentralGoogle Scholar
  29. 29.
    Auer TO, Del Bene F (2014) CRISPR/Cas9 and TALEN-mediated knock-in approaches in zebrafish. Methods 69:142–150PubMedGoogle Scholar
  30. 30.
    Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales APW, Li Z, Peterson RT, Yeh J-RJ, et al. (2015) Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523:481–485PubMedPubMedCentralGoogle Scholar
  31. 31.
    MacRae CA, Peterson RT (2015) Zebrafish as tools for drug discovery. Nat Rev Drug Discov 14:721–731PubMedGoogle Scholar
  32. 32.
    Rubinstein AL (2006) Zebrafish assays for drug toxicity screening. Expert Opin Drug Metab Toxicol 2:231–240PubMedGoogle Scholar
  33. 33.
    Alvarez CE, Sutcliffe JG (2002) Hypocretin is an early member of the incretin gene family. Neurosci Lett 324:169–172PubMedGoogle Scholar
  34. 34.
    Faraco JH, Appelbaum L, Marin W, Gaus SE, Mourrain P, Mignot E (2006) Regulation of hypocretin (orexin) expression in embryonic zebrafish. J Biol Chem 281:29753–29761PubMedGoogle Scholar
  35. 35.
    Huesa G, van den Pol AN, Finger TE (2005) Differential distribution of hypocretin (orexin) and melanin-concentrating hormone in the goldfish brain. J Comp Neurol 488:476–491PubMedGoogle Scholar
  36. 36.
    Kaslin J, Nystedt JM, Ostergård M, Peitsaro N, Panula P (2004) The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J Neurosci 24:2678–2689PubMedGoogle Scholar
  37. 37.
    Matsuda K, Azuma M, Kang KS (2012) Orexin system in teleost fish. Vitam Horm 89:341–361PubMedGoogle Scholar
  38. 38.
    Nakamachi T, Matsuda K, Maruyama K, Miura T, Uchiyama M, Funahashi H, Sakurai T, Shioda S (2006) Regulation by orexin of feeding behaviour and locomotor activity in the goldfish. J Neuroendocrinol 18:290–297PubMedGoogle Scholar
  39. 39.
    Appelbaum L, Wang GX, Maro GS, Mori R, Tovin A, Marin W, Yokogawa T, Kawakami K, Smith SJ, Gothilf Y, et al. (2009) Sleep-wake regulation and hypocretinmelatonin interaction in zebrafish. Proc Natl Acad Sci U S A 106:21942–21947PubMedPubMedCentralGoogle Scholar
  40. 40.
    Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF (2006) Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci 26:13400–13410PubMedGoogle Scholar
  41. 41.
    Panula P, Chen Y-C, Priyadarshini M, Kudo H, Semenova S, Sundvik M, Sallinen V (2010) The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases. Neurobiol Dis 40:46–57PubMedGoogle Scholar
  42. 42.
    Singh C, Oikonomou G, Prober DA (2015) Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish. eLife 4:e07000PubMedPubMedCentralGoogle Scholar
  43. 43.
    Sundvik M, Panula P (2015) Interactions of the orexin/hypocretin neurones and the histaminergic system. Acta Physiol (Oxf) 213:321–333Google Scholar
  44. 44.
    Sundvik M, Kudo H, Toivonen P, Rozov S, Chen Y-C, Panula P (2011) The histaminergic system regulates wakefulness and orexin/hypocretin neuron development via histamine receptor H1 in zebrafish. FASEB J 25:4338–4347PubMedGoogle Scholar
  45. 45.
    Yokogawa T, Marin W, Faraco J, Pézeron G, Appelbaum L, Zhang J, Rosa F, Mourrain P, Mignot E (2007) Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol 5:e277PubMedPubMedCentralGoogle Scholar
  46. 46.
    Cvetkovic-Lopes V, Bayer L, Dorsaz S, Maret S, Pradervand S, Dauvilliers Y, Lecendreux M, Lammers G-J, Donjacour CEHM, Du Pasquier RA, et al. (2010) Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients. J Clin Invest 120:713–719PubMedPubMedCentralGoogle Scholar
  47. 47.
    Dalal J, Roh JH, Maloney SE, Akuffo A, Shah S, Yuan H, Wamsley B, Jones WB, de Guzman Strong C, Gray PA, et al. (2013) Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation. Genes Dev 27:565–578PubMedPubMedCentralGoogle Scholar
  48. 48.
    Honda M, Arai T, Fukazawa M, Honda Y, Tsuchiya K, Salehi A, Akiyama H, Mignot E (2009) Absence of ubiquitinated inclusions in hypocretin neurons of patients with narcolepsy. Neurology 73:511–517PubMedPubMedCentralGoogle Scholar
  49. 49.
    Rosin DL, Weston MC, Sevigny CP, Stornetta RL, Guyenet PG (2003) Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2. J Comp Neurol 465:593–603PubMedGoogle Scholar
  50. 50.
    Liu J, Merkle FT, Gandhi AV, Gagnon JA, Woods IG, Chiu CN, Shimogori T, Schier AF, Prober DA (2015) Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9. Development 142:1113–1124PubMedPubMedCentralGoogle Scholar
  51. 51.
    Yelin-Bekerman L, Elbaz I, Diber A, Dahary D, Gibbs-Bar L, Alon S, Lerer-Goldshtein T, Appelbaum L (2015) Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a. Elife 4:e08638PubMedPubMedCentralGoogle Scholar
  52. 52.
    Cirelli C, Bushey D, Hill S, Huber R, Kreber R, Ganetzky B, Tononi G (2005) Reduced sleep in Drosophila Shaker mutants. Nature 434:1087–1092Google Scholar
  53. 53.
    Douglas CL, Vyazovskiy V, Southard T, Chiu S-Y, Messing A, Tononi G, Cirelli C (2007) Sleep in Kcna2 knockout mice. BMC Biol 5:42PubMedPubMedCentralGoogle Scholar
  54. 54.
    Appelbaum L, Skariah G, Mourrain P, Mignot E (2007) Comparative expression of p2x receptors and ecto-nucleoside triphosphate diphosphohydrolase 3 in hypocretin and sensory neurons in zebrafish. Brain Res 1174:66–75PubMedGoogle Scholar
  55. 55.
    Gandhi AV, Mosser EA, Oikonomou G, Prober DA (2015) Melatonin is required for the circadian regulation of sleep. Neuron 85:1193–1199PubMedPubMedCentralGoogle Scholar
  56. 56.
    Appelbaum L, Wang G, Yokogawa T, Skariah GM, Smith SJ, Mourrain P, Mignot E (2010) Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron 68:87–98PubMedPubMedCentralGoogle Scholar
  57. 57.
    Levitas-Djerbi T, Yelin-Bekerman L, Lerer-Goldshtein T, Appelbaum L (2015) Hypothalamic leptin-neurotensin-hypocretin neuronal networks in zebrafish. J Comp Neurol 523:831–848PubMedGoogle Scholar
  58. 58.
    Leinninger GM, Opland DM, Jo Y-H, Faouzi M, Christensen L, Cappellucci LA, Rhodes CJ, Gnegy ME, Becker JB, Pothos EN, et al. (2011) Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab 14:313–323PubMedPubMedCentralGoogle Scholar
  59. 59.
    Portugues R, Severi KE, Wyart C, Ahrens MB (2013) Optogenetics in a transparent animal: circuit function in the larval zebrafish. Curr Opin Neurobiol 23:119–126PubMedGoogle Scholar
  60. 60.
    Wyart C, Del Bene F (2011) Let there be light: zebrafish neurobiology and the optogenetic revolution. Rev Neurosci 22:121–130PubMedGoogle Scholar
  61. 61.
    Elbaz I, Foulkes NS, Gothilf Y, Appelbaum L (2013) Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish. Front Neural Circuits 7:9PubMedPubMedCentralGoogle Scholar
  62. 62.
    Elbaz I, Yelin-Bekerman L, Nicenboim J, Vatine G, Appelbaum L (2012) Genetic ablation of hypocretin neurons alters behavioral state transitions in zebrafish. J Neurosci 32:12961–12972PubMedGoogle Scholar
  63. 63.
    Carter ME, de Lecea L, Adamantidis A (2013) Functional wiring of hypocretin and LC-NE neurons: implications for arousal. Front Behav Neurosci 7:43PubMedPubMedCentralGoogle Scholar
  64. 64.
    Sundvik M, Panula P (2012) Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters. J Comp Neurol 520:3827–3845PubMedGoogle Scholar
  65. 65.
    Boules M, Li Z, Smith K, Fredrickson P, Richelson E (2013) Diverse roles of neurotensin agonists in the central nervous system. Front Endocrinol 4:36Google Scholar
  66. 66.
    Furutani N, Hondo M, Kageyama H, Tsujino N, Mieda M, Yanagisawa M, Shioda S, Sakurai T (2013) Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness states. PLoS One 8:e62391PubMedPubMedCentralGoogle Scholar
  67. 67.
    Kleczkowska P, Lipkowski AW (2013) Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation – a review. Eur J Pharmacol 716:54–60PubMedGoogle Scholar
  68. 68.
    Mustain WC, Rychahou PG, Evers BM (2011) The role of neurotensin in physiologic and pathologic processes. Curr Opin Endocrinol Diabetes Obes 18:75–82PubMedGoogle Scholar
  69. 69.
    Vincent JP, Mazella J, Kitabgi P (1999) Neurotensin and neurotensin receptors. Trends Pharmacol Sci 20:302–309Google Scholar
  70. 70.
    Cahill GM, Hurd MW, Batchelor MM (1998) Circadian rhythmicity in the locomotor activity of larval zebrafish. Neuroreport 9:3445–3449PubMedGoogle Scholar
  71. 71.
    Tovin A, Alon S, Ben-Moshe Z, Mracek P, Vatine G, Foulkes NS, Jacob-Hirsch J, Rechavi G, Toyama R, Coon SL, et al. (2012) Systematic identification of rhythmic genes reveals camk1gb as a new element in the circadian clockwork. PLoS Genet 8:e1003116PubMedPubMedCentralGoogle Scholar
  72. 72.
    Hurd MW, Debruyne J, Straume M, Cahill GM (1998) Circadian rhythms of locomotor activity in zebrafish. Physiol Behav 65:465–472PubMedGoogle Scholar
  73. 73.
    Naumann EA, Kampff AR, Prober DA, Schier AF, Engert F (2010) Monitoring neural activity with bioluminescence during natural behavior. Nat Neurosci 13:513–520PubMedPubMedCentralGoogle Scholar
  74. 74.
    Chen S, Chiu CN, McArthur KL, Fetcho JR, Prober DA (2016) TRP channel mediated neuronal activation and ablation in freely behaving zebrafish. Nat Methods 13:147–150PubMedGoogle Scholar
  75. 75.
    Nishimura Y, Okabe S, Sasagawa S, Murakami S, Ashikawa Y, Yuge M, Kawaguchi K, Kawase R, Tanaka T (2015) Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers. Front Pharmacol 6:257PubMedPubMedCentralGoogle Scholar
  76. 76.
    Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L (2007) Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450:420–424PubMedGoogle Scholar
  77. 77.
    Hishikawa Y, Wakamatsu H, Furuya E, Sugita Y, Masaoka S (1976) Sleep satiation in narcoleptic patients. Electroencephalogr Clin Neurophysiol 41:1–18PubMedGoogle Scholar
  78. 78.
    Mitler MM, Dement WC (1977) Sleep studies on canine narcolepsy: pattern and cycle comparisons between affected and normal dogs. Electroencephalogr Clin Neurophysiol 43:691–699PubMedGoogle Scholar
  79. 79.
    Montplaisir J, Billiard M, Takahashi S, Bell IR, Guilleminault C, Dement WC (1978) Twenty-four-hour recording in REM-narcoleptics with special reference to nocturnal sleep disruption. Biol Psychiatry 13:73–89PubMedGoogle Scholar
  80. 80.
    Zhang S, Zeitzer JM, Sakurai T, Nishino S, Mignot E (2007) Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy. J Physiol 581:649–663PubMedPubMedCentralGoogle Scholar
  81. 81.
    Kiwaki K, Kotz CM, Wang C, Lanningham-Foster L, Levine JA (2004) Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats. Am J Physiol Endocrinol Metab 286:E551–E559PubMedGoogle Scholar
  82. 82.
    Sweet DC, Levine AS, Billington CJ, Kotz CM (1999) Feeding response to central orexins. Brain Res 821:535–538PubMedGoogle Scholar
  83. 83.
    Williams RH, Alexopoulos H, Jensen LT, Fugger L, Burdakov D (2008) Adaptive sugar sensors in hypothalamic feeding circuits. Proc Natl Acad Sci U S A 105:11975–11980PubMedPubMedCentralGoogle Scholar
  84. 84.
    Matsuda K, Kang KS, Sakashita A, Yahashi S, Vaudry H (2011) Behavioral effect of neuropeptides related to feeding regulation in fish. Ann N Y Acad Sci 1220:117–126PubMedGoogle Scholar
  85. 85.
    Volkoff H, Bjorklund JM, Peter RE (1999) Stimulation of feeding behavior and food consumption in the goldfish, Carassius auratus, by orexin-A and orexin-B. Brain Res 846:204–209PubMedGoogle Scholar
  86. 86.
    Novak CM, Jiang X, Wang C, Teske JA, Kotz CM, Levine JA (2005) Caloric restriction and physical activity in zebrafish (Danio rerio). Neurosci Lett 383:99–104PubMedGoogle Scholar
  87. 87.
    Yokobori E, Kojima K, Azuma M, Kang KS, Maejima S, Uchiyama M, Matsuda K (2011) Stimulatory effect of intracerebroventricular administration of orexin A on food intake in the zebrafish, Danio rerio. Peptides 32:1357–1362PubMedGoogle Scholar
  88. 88.
    Klok MD, Jakobsdottir S, Drent ML (2007) The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 8:21–34PubMedGoogle Scholar
  89. 89.
    Alsop D, Vijayan MM (2009) Molecular programming of the corticosteroid stress axis during zebrafish development. Comp Biochem Physiol A Mol Integr Physiol 153:49–54PubMedGoogle Scholar
  90. 90.
    Berridge CW, España RA, Vittoz NM (2010) Hypocretin/orexin in arousal and stress. Brain Res 1314:91–102PubMedGoogle Scholar
  91. 91.
    Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S, Träskman-Bendz L, Goddard AW, Brundin L, Shekhar A (2010) A key role for orexin in panic anxiety. Nat Med 16:111–115PubMedGoogle Scholar
  92. 92.
    Kuru M, Ueta Y, Serino R, Nakazato M, Yamamoto Y, Shibuya I, Yamashita H (2000) Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 11:1977–1980PubMedGoogle Scholar
  93. 93.
    Russell SH, Small CJ, Dakin CL, Abbott CR, Morgan DG, Ghatei MA, Bloom SR (2001) The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats. J Neuroendocrinol 13:561–566PubMedGoogle Scholar
  94. 94.
    Suzuki M, Beuckmann CT, Shikata K, Ogura H, Sawai T (2005) Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like behavior. Brain Res 1044:116–121PubMedGoogle Scholar
  95. 95.
    Johnson PL, Molosh A, Fitz SD, Truitt WA, Shekhar A (2012) Orexin, stress, and anxiety/panic states. Prog Brain Res 198:133–161PubMedPubMedCentralGoogle Scholar
  96. 96.
    Samson WK, Bagley SL, Ferguson AV, White MM (2007) Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress. Am J Physiol Regul Integr Comp Physiol 292:R382–R387PubMedGoogle Scholar
  97. 97.
    Bonnavion P, Jackson AC, Carter ME, de Lecea L (2015) Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses. Nat Commun 6:6266PubMedPubMedCentralGoogle Scholar
  98. 98.
    Ramsay JM, Feist GW, Varga ZM, Westerfield M, Kent ML, Schreck CB (2006) Whole-body cortisol is an indicator of crowding stress in adult zebrafish, Danio rerio. Aquaculture 258:565–574Google Scholar
  99. 99.
    Ramsay JM, Feist GW, Varga ZM, Westerfield M, Kent ML, Schreck CB (2009) Whole-body cortisol response of zebrafish to acute net handling stress. Aquaculture 297:157–162PubMedPubMedCentralGoogle Scholar
  100. 100.
    Larson ET, O’Malley DM, Melloni RH (2006) Aggression and vasotocin are associated with dominant-subordinate relationships in zebrafish. Behav Brain Res 167:94–102PubMedGoogle Scholar
  101. 101.
    Spence R, Gerlach G, Lawrence C, Smith C (2008) The behaviour and ecology of the zebrafish, Danio rerio. Biol Rev Camb Philos Soc 83:13–34PubMedGoogle Scholar
  102. 102.
    Pavlidis M, Sundvik M, Chen Y-C, Panula P (2011) Adaptive changes in zebrafish brain in dominant-subordinate behavioral context. Behav Brain Res 225:529–537PubMedGoogle Scholar
  103. 103.
    Pavlidis M, Theodoridi A, Tsalafouta A (2015) Neuroendocrine regulation of the stress response in adult zebrafish, Danio rerio. Prog Neuropsychopharmacol Biol Psychiatry 60:121–131PubMedGoogle Scholar
  104. 104.
    Sakurai T (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8:171–181PubMedGoogle Scholar
  105. 105.
    Han F (2012) Sleepiness that cannot be overcome: narcolepsy and cataplexy. Respirology 17:1157–1165PubMedGoogle Scholar
  106. 106.
    Mahlios J, De la Herrán-Arita AK, Mignot E (2013) The autoimmune basis of narcolepsy. Curr Opin Neurobiol 23:767–773PubMedGoogle Scholar
  107. 107.
    Fronczek R, Overeem S, Lee SYY, Hegeman IM, van Pelt J, van Duinen SG, Lammers GJ, Swaab DF (2007) Hypocretin (orexin) loss in Parkinson’s disease. Brain J Neurol 130:1577–1585Google Scholar
  108. 108.
    Fronczek R, van Geest S, Frölich M, Overeem S, Roelandse FWC, Lammers GJ, Swaab DF (2012) Hypocretin (orexin) loss in Alzheimer’s disease. Neurobiol Aging 33:1642–1650PubMedGoogle Scholar
  109. 109.
    Thannickal TC, Lai Y-Y, Siegel JM (2007) Hypocretin (orexin) cell loss in Parkinson’s disease. Brain J Neurol 130:1586–1595Google Scholar
  110. 110.
    Nollet M, Leman S (2013) Role of orexin in the pathophysiology of depression: potential for pharmacological intervention. CNS Drugs 27:411–422PubMedGoogle Scholar
  111. 111.
    Holden T, Nguyen A, Lin E, Cheung E, Dehipawala S, Ye J, Tremberger G, Lieberman D, Cheung T (2013) Exploratory bioinformatics study of lncRNAs in Alzheimer’s disease mRNA sequences with application to drug development. Comput Math Methods Med 2013:1–8Google Scholar
  112. 112.
    Sigurgeirsson B, Thorsteinsson H, Arnardóttir H, Jóhannesdóttir IT, Karlsson KA (2011) Effects of modafinil on sleep-wake cycles in larval zebrafish. Zebrafish 8:133–140PubMedGoogle Scholar
  113. 113.
    Scammell TE, Estabrooke IV, McCarthy MT, Chemelli RM, Yanagisawa M, Miller MS, Saper CB (2000) Hypothalamic arousal regions are activated during modafinilinduced wakefulness. J Neurosci 20:8620–8628PubMedGoogle Scholar
  114. 114.
    Ishizuka T, Murotani T, Yamatodani A (2010) Modanifil activates the histaminergic system through the orexinergic neurons. Neurosci Lett 483:193–196PubMedGoogle Scholar
  115. 115.
    Bruni G, Lakhani P, Kokel D (2014) Discovering novel neuroactive drugs through high-throughput behavior-based chemical screening in the zebrafish. Front Pharmacol 5:153PubMedPubMedCentralGoogle Scholar
  116. 116.
    Tierney KB (2011) Behavioural assessments of neurotoxic effects and neurodegeneration in zebrafish. Biochim Biophys Acta 1812:381–389PubMedGoogle Scholar
  117. 117.
    Martineau PR, Mourrain P (2013) Tracking zebrafish larvae in group – status and perspectives. Methods (San Diego, Calif) 62:292–303Google Scholar
  118. 118.
    Ahrens MB, Li JM, Orger MB, Robson DN, Schier AF, Engert F, Portugues R (2012) Brain-wide neuronal dynamics during motor adaptation in zebrafish. Nature 485:471–477PubMedPubMedCentralGoogle Scholar
  119. 119.
    Ahrens MB, Orger MB, Robson DN, Li JM, Keller PJ (2013) Whole-brain functional imaging at cellular resolution using light-sheet microscopy. Nat Methods 10:413–420PubMedGoogle Scholar
  120. 120.
    Del Bene F, Wyart C, Robles E, Tran A, Looger L, Scott EK, Isacoff EY, Baier H (2010) Filtering of visual information in the tectum by an identified neural circuit. Science 330:669–673PubMedGoogle Scholar
  121. 121.
    Kokel D, Bryan J, Laggner C, White R, Cheung CYJ, Mateus R, Healey D, Kim S, Werdich AA, Haggarty SJ, et al. (2010) Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat Chem Biol 6:231–237PubMedPubMedCentralGoogle Scholar
  122. 122.
    Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, et al. (2010) Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327:348–351PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 2.5 International License (http://creativecommons.org/licenses/by-nc/2.5/), which permits any noncommercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Authors and Affiliations

  • Idan Elbaz
    • 1
  • Talia Levitas-Djerbi
    • 1
  • Lior Appelbaum
    • 1
  1. 1.The Mina & Everard Goodman Faculty of Life Sciences and The Leslie and Susan Gonda Multidisciplinary Brain Research CenterBar-Ilan UniversityRamat GanIsrael

Personalised recommendations