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Physiological Characteristics of Hypocretin/Orexin Neurons

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Hypocretins

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11. References

  1. L. de Lecea, T. S. Kilduff, C. Peyron, X. Gao, P. E. Foye, P. E. Danielson, C. Fukuhara, E. L. Battenberg, V. T. Gautvik, F. S. Bartlett, 2nd, W. N. Frankel, A. N. van den Pol, F. E. Bloom, K. M. Gautvik and J. G. Sutcliffe, The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity, Proc Natl Acad Sci U S A. 95, 322–7 (1998).

    Article  PubMed  Google Scholar 

  2. T. Sakurai, A. Amemiya, M. Ishii, I. Matsuzaki, R. M. Chemelli, H. Tanaka, S. C. Williams, J. A. Richardson, G. P. Kozlowski, S. Wilson, J. R. Arch, R. E. Buckingham, A. C. Haynes, S. A. Carr, R. S. Annan, D. E. McNulty, W. S. Liu, J. A. Terrett, N. A. Elshourbagy, D. J. Bergsma and M. Yanagisawa, Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior, Cell. 92, 573–85 (1998).

    Article  PubMed  CAS  Google Scholar 

  3. C. Peyron, D. K. Tighe, A. N. van den Pol, L. de Lecea, H. C. Heller, J. G. Sutcliffe and T. S. Kilduff, Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems, J Neurosci. 18, 9996–10015 (1998).

    PubMed  CAS  Google Scholar 

  4. A. N. van den Pol, Hypothalamic hypocretin (orexin): robust innervation of the spinal cord, J. Neurosci. 19, 3171–82 (1999).

    PubMed  Google Scholar 

  5. J. N. Marcus, C. J. Aschkenasi, C. E. Lee, R. M. Chemelli, C. B. Saper, M. Yanagisawa and J. K. Elmquist, Differential expression of orexin receptors 1 and 2 in the rat brain, J Comp Neurol. 435, 6–25. (2001).

    Article  PubMed  CAS  Google Scholar 

  6. P. Trivedi, H. Yu, D. J. MacNeil, L. H. Van der Ploeg and X. M. Guan, Distribution of orexin receptor mRNA in the rat brain, FEBS Lett. 438, 71–5 (1998).

    Article  PubMed  CAS  Google Scholar 

  7. E. E. Abrahamson, R. K. Leak and R. Y. Moore, The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems, Neuroreport. 12, 435–40. (2001).

    Article  PubMed  CAS  Google Scholar 

  8. F. Torrealba, M. Yanagisawa and C. B. Saper, Colocalization of orexin a and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats, Neuroscience. 119, 1033–44 (2003).

    Article  PubMed  CAS  Google Scholar 

  9. D. L. Rosin, M. C. Weston, C. P. Sevigny, R. L. Stornetta and P. G. Guyenet, Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2, J Comp Neurol. 465, 593–603 (2003).

    Article  PubMed  CAS  Google Scholar 

  10. R. T. Fremeau, Jr., M. D. Troyer, I. Pahner, G. O. Nygaard, C. H. Tran, R. J. Reimer, E. E. Bellocchio, D. Fortin, J. Storm-Mathisen and R. H. Edwards, The expression of vesicular glutamate transporters defines two classes of excitatory synapse, Neuron. 31, 247–60 (2001).

    Article  PubMed  CAS  Google Scholar 

  11. T. C. Chou, A. A. Bjorkum, S. E. Gaus, J. Lu, T. E. Scammell and C. B. Saper, Afferents to the ventrolateral preoptic nucleus, J Neurosci. 22, 977–90 (2002).

    PubMed  CAS  Google Scholar 

  12. D. Georgescu, V. Zachariou, M. Barrot, M. Mieda, J. T. Willie, A. J. Eisch, M. Yanagisawa, E. J. Nestler and R. J. DiLeone, Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal, J Neurosci. 23, 3106–11 (2003).

    PubMed  CAS  Google Scholar 

  13. C. Peyron, J. Faraco, W. Rogers, B. Ripley, S. Overeem, Y. Charnay, S. Nevsimalova, M. Aldrich, D. Reynolds, R. Albin, R. Li, M. Hungs, M. Pedrazzoli, M. Padigaru, M. Kucherlapati, J. Fan, R. Maki, G. J. Lammers, C. Bouras, R. Kucherlapati, S. Nishino and E. Mignot, A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains, Nat Med. 6, 991–997 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. T. C. Thannickal, R. Y. Moore, R. Nienhuis, L. Ramanathan, S. Gulyani, M. Aldrich, M. Cornford and J. M. Siegel, Reduced number of hypocretin neurons in human narcolepsy, Neuron. 27, 469–74. (2000).

    Article  PubMed  CAS  Google Scholar 

  15. R. M. Chemelli, J. T. Willie, C. M. Sinton, J. K. Elmquist, T. Scammell, C. Lee, J. A. Richardson, S. C. Williams, Y. Xiong, Y. Kisanuki, T. E. Fitch, M. Nakazato, R. E. Hammer, C. B. Saper and M. Yanagisawa, Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation, Cell. 98, 437–51 (1999).

    Article  PubMed  CAS  Google Scholar 

  16. L. Lin, J. Faraco, R. Li, H. Kadotani, W. Rogers, X. Lin, X. Qiu, P. J. de Jong, S. Nishino and E. Mignot, The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene, Cell. 98, 365–76 (1999).

    Article  PubMed  CAS  Google Scholar 

  17. A. N. van den Pol, Narcolepsy: a neurodegenerative disease of the hypocretin system?, Neuron. 27, 415–8. (2000).

    Article  PubMed  Google Scholar 

  18. J. Hara, C. T. Beuckmann, T. Nambu, J. T. Willie, R. M. Chemelli, C. M. Sinton, F. Sugiyama, K. Yagami, K. Goto, M. Yanagisawa and T. Sakurai, Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity, Neuron. 30, 345–54. (2001).

    Article  PubMed  CAS  Google Scholar 

  19. S. Nishino, B. Ripley, S. Overeem, G. J. Lammers and E. Mignot, Hypocretin (orexin) deficiency in human narcolepsy [letter] [In Process Citation], Lancet. 355, 39–40 (2000).

    Article  PubMed  CAS  Google Scholar 

  20. Y. Li, X. B. Gao, T. Sakurai and A. N. van den Pol, Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system, Neuron. 36, 1169–81 (2002).

    Article  PubMed  CAS  Google Scholar 

  21. M. Usher, J. D. Cohen, D. Servan-Schreiber, J. Rajkowski and G. Aston-Jones, The role of locus coeruleus in the regulation of cognitive performance, Science. 283, 549–54 (1999).

    Article  PubMed  CAS  Google Scholar 

  22. T. L. Horvath, C. H. Warden, M. Hajos, A. Lombardi, F. Goglia and S. Diano, Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers, J Neurosci. 19, 10417–27 (1999).

    PubMed  CAS  Google Scholar 

  23. M. N. Alam, H. Gong, T. Alam, R. Jaganath, D. McGinty and R. Szymusiak, Sleep-waking discharge patterns of neurons recorded in the rat perifornical lateral hypothalamic area, J Physiol. 538, 619–31 (2002)..

    Article  PubMed  CAS  Google Scholar 

  24. C. Broberger, L. de Lecea, J. G. Sutcliffe and T. Hökfelt, Hypocretin/orexin-and melanin-concentrating hormone expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to neuropeptide Y innervation, J. Comp. Neurol. 402, 460–474 (1998).

    Article  PubMed  CAS  Google Scholar 

  25. C. F. Elias, C. B. Saper, E. Maratos-Flier, N. A. Tritos, C. Lee, J. Kelly, J. B. Tatro, G. E. Hoffman, M. M. Ollmann, G. S. Barsh, T. Sakurai, M. Yanagisawa and J. M. Elmquist, Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area, J Comp Neurol. 402, 442–459 (1998).

    Article  PubMed  CAS  Google Scholar 

  26. A. N. Van Den Pol, C. Acuna-Goycolea, K. R. Clark and P. K. Ghosh, Physiological Properties of Hypothalamic MCH Neurons Identified with Selective Expression of Reporter Gene after Recombinant Virus Infection, Neuron. 42, 635–52 (2004).

    Article  PubMed  Google Scholar 

  27. A. Yamanaka, C. T. Beuckmann, J. T. Willie, J. Hara, N. Tsujino, M. Mieda, M. Tominaga, K. Yagami, F. Sugiyama, K. Goto, M. Yanagisawa and T. Sakurai, Hypothalamic orexin neurons regulate arousal according to energy balance in mice, Neuron. 38, 701–13 (2003).

    Article  PubMed  CAS  Google Scholar 

  28. E. Eggermann, L. Bayer, M. Serafin, B. Saint-Mleux, L. Bernheim, D. Machard, B. E. Jones and M. Muhlethaler, The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarization, J Neurosci. 23, 1557–62 (2003).

    PubMed  CAS  Google Scholar 

  29. A. N. van den Pol, J. P. Wuarin and F. E. Dudek, Glutamate, the dominant excitatory transmitter in neuroendocrine regulation, Science. 250, 1276–8 (1990).

    Article  PubMed  Google Scholar 

  30. C. Decavel and A. N. Van den Pol, GABA: a dominant neurotransmitter in the hypothalamus, J Comp Neurol. 302, 1019–37 (1990).

    Article  PubMed  CAS  Google Scholar 

  31. J. J. Hagan, R. A. Leslie, S. Patel, M. L. Evans, T. A. Wattam, S. Holmes, C. D. Benham, S. G. Taylor, C. Routledge, P. Hemmati, R. P. Munton, T. E. Ashmeade, A. S. Shah, J. P. Hatcher, P. D. Hatcher, D. N. Jones, M. I. Smith, D. C. Piper, A. J. Hunter, R. A. Porter and N. Upton, Orexin A activates locus coeruleus cell firing and increases arousal in the rat, Proc Natl Acad Sci U S A. 96, 10911–6 (1999).

    Article  PubMed  CAS  Google Scholar 

  32. A. N. van den Pol, P. K. Ghosh, R. J. Liu, Y. Li, G. K. Aghajanian and X. B. Gao, Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP-expressing locus coeruleus, J Physiol. 541, 169–85 (2002).

    Article  PubMed  Google Scholar 

  33. P. Bourgin, S. Huitrón-Reséndiz, A. Spier, V. Fabre, B. Morte, J. Criado, J. Sutcliffe, S. Henriksen and L. de Lecea, Hypocretin-1 modulates REM sleep through activation of locus coeruleus neurons, J. Neurosci. 20, 7760–5 (2000).

    PubMed  CAS  Google Scholar 

  34. A. Ivanov and G. Aston-Jones, Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons, Neuroreport. 11, 1755–8. (2000).

    Article  PubMed  CAS  Google Scholar 

  35. R. J. Liu, A. N. van den Pol and G. K. Aghajanian, Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions, J Neurosci. 22, 9453–64 (2002).

    PubMed  CAS  Google Scholar 

  36. R. E. Brown, O. A. Sergeeva, K. S. Eriksson and H. L. Haas, Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline), J Neurosci. 22, 8850–9 (2002).

    PubMed  CAS  Google Scholar 

  37. B. A. Baldo, R. A. Daniel, C. W. Berridge and A. E. Kelley, Overlapping distributions of orexin/hypocretin-and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress, J Comp Neurol. 464, 220–37 (2003).

    Article  PubMed  Google Scholar 

  38. S. Burlet, C. J. Tyler and C. S. Leonard, Direct and indirect excitation of laterodorsal tegmental neurons by Hypocretin/Orexin peptides: implications for wakefulness and narcolepsy, J Neurosci. 22, 2862–72 (2002).

    PubMed  CAS  Google Scholar 

  39. E. Eggermann, M. Serafin, L. Bayer, D. Machard, B. Saint-Mleux, B. E. Jones and M. Muhlethaler, Orexins/hypocretins excite basal forebrain cholinergic neurones, Neuroscience. 108, 177–81 (2001).

    Article  PubMed  CAS  Google Scholar 

  40. M. Wu, L. Zaborszky, T. Hajszan, A. N. van den Pol and M. Alreja, Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons, J Neurosci. 24, 3527–36 (2004).

    Article  PubMed  CAS  Google Scholar 

  41. K. S. Eriksson, O. Sergeeva, R. E. Brown and H. L. Haas, Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus, J Neurosci. 21, 9273–9 (2001).

    PubMed  CAS  Google Scholar 

  42. A. N. van den Pol, X. B. Gao, K. Obrietan, T. S. Kilduff and A. B. Belousov, Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin, J Neurosci. 18, 7962–71 (1998).

    PubMed  Google Scholar 

  43. A. N. van den Pol, P. R. Patrylo, P. K. Ghosh and X. B. Gao, Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin), J Comp Neurol. 433, 349–363. (2001)..

    Article  Google Scholar 

  44. C. Acuña-Goycolea, Y. Li and A. N. Van Den Pol, Group III metabotropic glutamate receptors maintain tonic inhibition of excitatory synaptic input to hypocretin/orexin neurons, J Neurosci. 24, 3013–22 (2004).

    Article  PubMed  Google Scholar 

  45. S. L. Jin, V. K. Han, J. G. Simmons, A. C. Towle, J. M. Lauder and P. K. Lund, Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study, J Comp Neurol. 271, 519–32 (1988).

    Article  PubMed  CAS  Google Scholar 

  46. H. Yamamoto, T. Kishi, C. E. Lee, B. J. Choi, H. Fang, A. N. Hollenberg, D. J. Drucker and J. K. Elmquist, Glucagon-like peptide-1-responsive catecholamine neurons in the area postrema link peripheral glucagon-like peptide-1 with central autonomic control sites, J Neurosci. 23, 2939–46 (2003).

    PubMed  CAS  Google Scholar 

  47. I. Merchenthaler, M. Lane and P. Shughrue, Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system, J Comp Neurol. 403, 261–80 (1999).

    Article  PubMed  CAS  Google Scholar 

  48. C. Acuna-Goycolea, Y. Li and A. N. Van Den Pol, Group III metabotropic glutamate receptors maintain tonic inhibition of excitatory synaptic input to hypocretin/orexin neurons, J Neurosci. 24, 3013–22 (2004).

    Article  PubMed  CAS  Google Scholar 

  49. M. López, L. Seoane, M. C. García, F. Lago, F. F. Casanueva, R. Senaris and C. Diéguez, Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus, Biochem Biophys Res Commun. 269, 41–5 (2000).

    Article  PubMed  Google Scholar 

  50. L. Bayer, C. Colard, N. U. Nguyen, P. Y. Risold, D. Fellmann and B. Griffond, Alteration of the expression of the hypocretin (orexin) gene by 2-deoxyglucose in the rat lateral hypothalamic area, Neuroreport. 11, 531–3 (2000).

    Article  PubMed  CAS  Google Scholar 

  51. Y. Yamamoto, Y. Ueta, Y. Date, M. Nakazato, Y. Hara, R. Serino, M. Nomura, I. Shibuya, S. Matsukura and H. Yamashita, Down regulation of the prepro-orexin gene expression in genetically obese mice, Brain Res Mol Brain Res. 65, 14–22 (1999).

    Article  PubMed  CAS  Google Scholar 

  52. K. W. Nowak, P. Mackowiak, M. M. Switonska, M. Fabis and L. K. Malendowicz, Acute orexin effects on insulin secretion in the rat: in vivo and in vitro studies, Life Sci. 66, 449–54 (2000).

    Article  PubMed  CAS  Google Scholar 

  53. B. Griffond, P. Y. Risold, C. Jacquemard, C. Colard and D. Fellmann, Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat lateral hypothalamic area, Neurosci Lett. 262, 77–80 (1999).

    Article  PubMed  CAS  Google Scholar 

  54. T. Moriguchi, T. Sakurai, T. Nambu, M. Yanagisawa and K. Goto, Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia, Neurosci Lett. 264, 101–4 (1999).

    Article  PubMed  CAS  Google Scholar 

  55. A. Yamanaka, C. T. Beuckmann, J. T. Willie, J. Hara, N. Tsujino, M. Mieda, M. Tominaga, K. Yagami, F. Sugiyama, K. Goto, M. Yanagisawa and T. Sakurai, Hypothalamic orexin neurons regulate arousal according to energy balance in mice, Neuron. 38, 701–13 (2003).

    Article  PubMed  CAS  Google Scholar 

  56. T. L. Horvath, C. H. Warden, M. Hajos, A. Lombardi, F. Goglia and S. Diano, Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers, J Neurosci. 19, 10417–27 (1999).

    PubMed  CAS  Google Scholar 

  57. T. J. Grudt, A. N. van Den Pol and E. R. Perl, Hypocretin-2 (orexin-B) modulation of superficial dorsal horn activity in rat, J Physiol. 538, 517–525 (2002).

    Article  PubMed  CAS  Google Scholar 

  58. J. Yamuy, S. J. Fung, M. Xi and M. H. Chase, Hypocretinergic control of spinal cord motoneurons, J Neurosci. 24, 5336–45 (2004).

    Article  PubMed  CAS  Google Scholar 

  59. B. N. Smith, S. F. Davis, A. N. Van Den Pol and W. Xu, Selective enhancement of excitatory synaptic activity in the rat nucleus tractus solitarius by hypocretin 2, Neuroscience. 115, 707–14 (2002).

    Article  PubMed  CAS  Google Scholar 

  60. L. L. Hwang, C. T. Chen and N. J. Dun, Mechanisms of orexin-induced depolarizations in rat dorsal motor nucleus of vagus neurones in vitro, J Physiol. 537, 511–20 (2001).

    Article  PubMed  CAS  Google Scholar 

  61. L. Bayer, C. Colard, N. U. Nguyen, P. Y. Risold, D. Fellmann and B. Griffond, Alteration of the expression of the hypocretin (orexin) gene by 2-deoxyglucose in the rat lateral hypothalamic area, Neuroreport. 11, 531–3 (2000).

    Article  PubMed  CAS  Google Scholar 

  62. J. H. Peever, Y. Y. Lai and J. M. Siegel, Excitatory effects of hypocretin-1 (orexin-A) in the trigeminal motor nucleus are reversed by NMDA antagonism, J Neurophysiol. 89, 2591–600 (2003).

    Article  PubMed  CAS  Google Scholar 

  63. B. Yang and A. V. Ferguson, Orexin-A depolarizes nucleus tractus solitarius neurons through effects on nonselective cationic and K+ conductances, J Neurophysiol. 89, 2167–75 (2003).

    Article  PubMed  CAS  Google Scholar 

  64. M. F. Wu, J. John, N. Maidment, H. A. Lam and J. M. Siegel, Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement, Am J Physiol Regul Integr Comp Physiol. 283, R1079–86 (2002).

    PubMed  Google Scholar 

  65. D. Burdakov, B. Liss and F. M. Ashcroft, Orexin excites GABAergic neurons of the arcuate nucleus by activating the sodium—calcium exchanger, J Neurosci. 23, 4951–7 (2003).

    PubMed  CAS  Google Scholar 

  66. K. A. Kohlmeier, T. Inoue and C. S. Leonard, Hypocretin/Orexin peptide signalling in the ascending arousal system: Elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum, J Neurophysiol. (2004).

    Google Scholar 

  67. T. M. Korotkova, K. S. Eriksson, H. L. Haas and R. E. Brown, Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro, Regul Pept. 104, 83–89 (2002).

    Article  PubMed  CAS  Google Scholar 

  68. S. F. Davis, K. W. Williams, W. Xu, N. R. Glatzer and B. N. Smith, Selective enhancement of synaptic inhibition by hypocretin (orexin) in rat vagal motor neurons: implications for autonomic regulation, J Neurosci. 23, 3844–54 (2003).

    PubMed  CAS  Google Scholar 

  69. T. Sakurai, T. Moriguchi, K, Furuya, N. Kajiwara, T. Nakamura, M. Yanagisawa and K. Goto, Structure and function of human prepro-orexin gene, J. Biol. Chem., 274: 17771–17776 (1999).

    Article  PubMed  CAS  Google Scholar 

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van den Pol, A.N. (2005). Physiological Characteristics of Hypocretin/Orexin Neurons. In: de Lecea, L., Sutcliffe, J.G. (eds) Hypocretins. Springer, Boston, MA. https://doi.org/10.1007/0-387-25446-3_8

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