Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2

Journal of Comparative Neurology

Volumn 465, Issue 4, 2003, Pages 593-603

  Rosin, Diane L ^a,b   Weston, Matthew C ^a   Sevigny, Charles P ^a   Stornetta, Ruth L ^a   Guyenet, Patrice G ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

Author keywords

Cardiovascular regulation; Feeding; GABA; GAD67; Glutamate; Hypothalamus; In situ hybridization; Narcolepsy; Obesity

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID RECEPTOR; GLUTAMATE RECEPTOR; GLUTAMATE TRANSPORTER; NEUROPEPTIDE; OREXIN; UNCLASSIFIED DRUG; VESICULAR GLUTAMATE TRANSPORTER 1; VESICULAR GLUTAMATE TRANSPORTER 2;

ANIMAL CELL; ANIMAL TISSUE; APPETITE; ARTICLE; BRAIN CORTEX; CELL POPULATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; EXCITATION; FOREBRAIN; HYPOTHALAMUS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; MALE; NARCOLEPSY; NERVE CELL; NERVE PROJECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; RAT; RNA PROBE; THALAMUS;

ANIMALS; APPETITE REGULATION; CARRIER PROTEINS; EFFERENT PATHWAYS; GAMMA-AMINOBUTYRIC ACID; GLUTAMATE DECARBOXYLASE; GLUTAMIC ACID; HYPOTHALAMUS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; ISOENZYMES; MALE; MEMBRANE TRANSPORT PROTEINS; NARCOLEPSY; NEURONS; NEUROPEPTIDES; RATS; RATS, SPRAGUE-DAWLEY; RNA, MESSENGER; SYNAPTIC TRANSMISSION; VESICULAR GLUTAMATE TRANSPORT PROTEIN 1; VESICULAR GLUTAMATE TRANSPORT PROTEIN 2; VESICULAR TRANSPORT PROTEINS;

EID: 0141593423     PISSN: 00219967     EISSN: None     Source Type: Journal    
DOI: 10.1002/cne.10860     Document Type: Article

References (84)

1. Abrahamson EE, Leak RK, Moore RY. 2001. The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 12:435-440.
2. Aihara Y, Mashima H, Onda H, Hisano S, Kasuya H, Hori T, Yamada S, Tomura H, Yamada Y, Inoue I, Kojima I, Takeda J. 2000. Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter. J Neurochem 74:2622-2625.
3. Antunes VR, Brailoiu GC, Kwok EH, Scruggs P, Dun NJ. 2001. Orexins/hypocretins excite rat sympathetic preganglionic neurons in vivo and in vitro. Am J Physiol Regul Integr Comp Physiol 281:R1801-R1807.
4. Bai LQ, Xu H, Collins JF, Ghishan FK. 2001. Molecular and functional analysis of a novel neuronal vesicular glutamate transporter. J Biol Chem 276:36764-36769.
5. Bayer L, Eggermann E, Serafin M, Saint-Mleux B, Machard D, Jones B, Mühlethaler M. 2001. Orexins (hypocretins) directly excite tuberomammillary neurons. Eur J Neurosci 14:1571-1575.
6. Bellocchio EE, Hu H, Pohorille A, Chan J, Pickel VM, Edwards RH. 1998. The localization of the brain-specific inorganic phosphate transporter suggests a specific presynaptic role in glutamatergic transmission. J Neurosci 18:8648-8659.
7. Bellocchio EE, Reimer RJ, Fremeau RT Jr, Edwards RH. 2000. Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter [see comments]. Science 289:957-960.
8. Broberger C. 1999. Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y. Brain Res 848:101-113.
9. Broberger C, De Lecea L, Sutcliffe JG, Hokfelt T. 1998. Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. J Comp Neurol 402:460-474.
10. Brown RE, Sergeeva O, Eriksson KS, Haas HL. 2001. Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat. Neuropharmacology 40:457-459.
11. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M. 1999. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation [see comments]. Cell 98:437-451.
12. Chen CT, Hwang LL, Chang JK, Dun NJ. 2000. Pressor effects of orexins injected intracisternally and to rostral ventrolateral medulla of anesthetized rats. Am J Physiol Regul Integr Comp Physiol 278:R692-R697.
13. Chou TC, Lee CE, Lu J, Elmquist JK, Hara J, Willie JT, Beuckmann CT, Chemelli RM, Sakurai T, Yanagisawa M, Saper CB, Scammell TE. 2001. Orexin (hypocretin) neurons contain dynorphin. J Neurosci 21: NIL19-NIL24.
14. Commons KG and Milner TA. 1995. Ultrastructural heterogeneity of enkephalin-containing terminals in the rat hippocampal formation. J Comp Neurol 358:324-342.
15. Conner-Kerr TA, Simmons DR, Peterson GM, Terrian DM. 1993. Evidence for the corelease of dynorphin and glutamate from rat hippocampal mossy fiber terminals. J Neurochem 61:627-636.
16. Cutler DJ, Morris R, Sheridhar V, Wattam TA, Holmes S, Patel S, Arch JR, Wilson S, Buckingham RE, Evans ML, Leslie RA, Williams G. 1999. Differential distribution of orexin-A and orexin-B immunoreactivity in the rat brain and spinal cord. Peptides 20:1455-1470.
17. Cutler DJ, Morris R, Evans ML, Leslie RA, Arch JR, Williams G, 2001. Orexin-A immunoreactive neurons in the rat hypothalamus do not contain neuronal nitric oxide synthase (nNOS). Peptides 22:123-128.
18. 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 USA 96:748-753.
19. Date Y, Mondal MS, Matsukura S, Nakazato M. 2000. Distribution of orexin-A and orexin-B (hypocretins) in the rat spinal cord. Neurosci Lett 288:87-90.
20. De Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS2, Frankel WN, Van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. 1998. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322-327.
21. Ding YQ, Kaneko T, Nomura S, Mizuno N. 1996. Immunohistochemical localization of m-opioid receptors in the central nervous system of the rat. J Comp Neurol 367:375-402.
22. Dun NJ, Le Dun S, Chen CT, Hwang LL, Kwok EH, Chang JK. 2000. Orexins: a role in medullary sympathetic outflow. Regul Pept 96:65-70.
23. Eggermann E, Serafin M, Bayer L, Machard D, Saint-Mleux B, Jones BE, Mühlethaler M. 2001. Orexins/hypocretins excite basal forebrain cholinergic neurones. Neuroscience 108:177-181.
24. Eriksson KS, Sergeeva O, Brown RE, Haas HL. 2001. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J Neurosci 21:9273-9279.
25. Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ. 1991. Two genes encode distinct glutamate decarboxylases. Neuron 7:91-100.
26. Esclapez M, Tillakaratne NJ, Tobin AJ, Houser CR. 1993. Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. J Comp Neurol 331:339-362.
27. Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, Saper CB, Scammell TE. 2001. Fos expression in orexin neurons varies with behavioral state. J Neurosci 21:1656-1662.
28. Fadel J, Bubser M, Deutch AY. 2002. Differential activation of orexin neurons by antipsychotic drugs associated with weight gain. J Neurosci 22:6742-6746.
29. Fremeau RT Jr, Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, Bellocchio EE, Fortin D, Storm-Mathisen J, Edwards RH. 2001. The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 31:247-260.
30. Fremeau RT Jr, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH. 2002. The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci USA 99:14488-14493.
31. Fujiyama F, Furuta T, Kaneko T. 2001. Immunocytochemical localization of candidates for vesicular glutamate transporters in the rat cerebral cortex. J Comp Neurol 435:379-387.
32. Gall C, Brecha N, Karten HJ, Chang KJ. 1981. Localization of enkephalin-like immunoreactivity to identified axonal and neuronal populations of the rat hippocampus. J Comp Neurol 198:335-350.
33. Gautvik KM, De Lecea L, Gautvik VT, Danielson PE, Tranque P, Dopazo A, Bloom FE, Sutcliffe JG. 1996. Overview of the most prevalent hypothalamus-specific mRNAs, as identified by directional tag PCR subtraction. Proc Natl Acad Sci USA 93:8733-8738.
34. Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S. 2002. A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci 22:5442-5451.
35. Guyenet PG, Stornetta RL, Riley T, Norton FR, Rosin DL, Lynch KR. 1994. Alpha 2A-adrenergic receptors are present in lower brainstem catecholaminergic and serotonergic neurons innervating spinal cord [published erratum appears in Brain Res 1994;646:356-357]. Brain Res 638:285-294.
36. Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S, Benham CD, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Shah AS, Hatcher JP, Hatcher PD, Jones DN, Smith MI, Piper DC, Hunter AJ, Porter RA, Upton N. 1999. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci USA 96:10911-10916.
37. Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, Sakurai T. 2001. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30:345-354.
38. Herzog E, Bellenchi GC, Gras C, Bernard V, Ravassard P, Bedet C, Gasnier B, Giros B, El Mestikawy S. 2001. The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. J Neurosci 21:NIL1-NIL6.
39. +-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain. Mol Brain Res 83:34-43.
40. Hokfelt T, Broberger C, Xu ZQ, Sergeyev V, Ubink R, Diez M. 2000. Neuropeptides - an overview. Neuropharmacology 39:1337-1356.
41. Horvath TL, Peyron C, Diano S, Ivanov A, Aston-Jones G, Kilduff TS, Van den Pol AN. 1999. Hypocretin (Orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J Comp Neurol 415:145-159.
42. Hwang LL, Chen CT, Dun NJ. 2001. Mechanisms of orexin-induced depolarizations in rat dorsal motor nucleus of vagus neurones in vitro. J Physiol (Lond) 537:511-520.
43. Ivanov A, Aston-Jones G. 2000. Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons. Neuroreport 11:1755-1758.
44. Law PY, Wong YH, Loh HH. 2000. Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol 40:389-430.
45. 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 98:365-376.
46. Machado BH, Bonagamba LG, Dun SL, Kwok EH, Dun NJ. 2002. Pressor response to microinjection of orexin/hypocretin into rostral ventrolateral medulla of awake rats. Regul Pept 104:75-81.
47. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK. 2001. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 435:6-25.
48. Matsumura K, Tsuchihashi T, Abe I. 2001. Central orexin-A augments sympathoadrenal outflow in conscious rabbits. Hypertension 37:1382-1387.
49. Mignot E. 2001. A commentary on the neurobiology of the hypocretin/ orexin system. Neuropsychopharmacology 25:S5-S13.
50. Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K. 1999. Distribution of orexin neurons in the adult rat brain. Brain Res 827:243-260.
51. Ni B, Rosteck PR Jr, Nadi NS, Paul SM. 1994. Cloning and expression of a cDNA encoding a brain-specific Na(+)-dependent inorganic phosphate cotransporter. Proc Natl Acad Sci USA 91:5607-5611.
52. Ni B, Wu X, Yan GM, Wang J, Paul SM. 1995. Regional expression and cellular localization of the Na(+)-dependent inorganic phosphate cotransporter of rat brain. J Neurosci 15:5789-5799.
53. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. 2000. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355:39-40.
54. Nishino S, Ripley B, Overeem S, Nevsimalova S, Lammers GJ, Vankova J, Okun M, Rogers W, Brooks S, Mignot E. 2001. Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy. Ann Neurol 50:381-388.
55. Ogura M, Kita H. 2000. Dynorphin exerts both postsynaptic and presynaptic effects in the globus pallidus of the rat. J Neurophysiol 83:3366-3376.
56. Otis TS. 2001. Vesicular glutamate transporters in cognito. Neuron 29:11-14.
57. Paxinos G, Watson C. 1998. The rat brain in sterotaxic coordinates. Academic Press, San Diego.
58. 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 18:9996-10015.
59. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. 2000. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6:991-997.
60. 2C-adrenergic receptor-like immunoreactivity in the rat central nervous system. J Comp Neurol 372:135-165.
61. Sakata-Haga H, Kanemoto M, Maruyama D, Hoshi K, Mogi K, Narita M, Okado N, Ikeda Y, Nogami H, Fukui Y, Kojima I, Takeda J, Hisano S. 2001. Differential localization and colocalization of two neuron-types of sodium-dependent inorganic phosphate cotransporters in rat forebrain. Brain Res 902:143-155.
62. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richarson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M. 1998. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573-585.
63. Samson WK, Gosnell B, Chang JK, Resch ZT, Murphy TC. 1999. Cardiovascular regulatory actions of the hypocretins in brain. Brain Res 831:248-253.
64. Schafer MKH, Varoqui H, Defamie N, Weihe E, Erickson JD. 2002. Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734-50748.
65. Shirasaka T, Nakazato M, Matsukura S, Takasaki M, Kannan H. 1999. Sympathetic and cardiovascular actions of orexins in conscious rats. Am J Physiol Regul Integr Comp Physiol 277:R1780-R1785.
66. Shirasaka T, Miyahara S, Kunitake T, Jin QH, Kato K, Takasaki M, Kannan H. 2001. Orexin depolarizes rat hypothalamic paraventricular nucleus neurons. Am J Physiol Regul Integr Comp Physiol 281:R1114-R1118.
67. Shuster SJ, Riedl M, Li X, Vulchanova L, Elde R. 2000. The kappa opioid receptor and dynorphin co-localize in vasopressin magnocellular neurosecretory neurons in guinea-pig hypothalamus. Neuroscience 96:373-383.
68. Steiner H, Gerfen CR. 1998. Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior. Exp Brain Res 123:60-76.
69. Stornetta RL, Guyenet PG. 1999. Distribution of glutamic acid decarboxylase mRNA-containing neurons in rat medulla projecting to thoracic spinal cord in relation to monoaminergic brainstem neurons. J Comp Neurol 407:367-380.
70. Stornetta RL, Schreihofer AM, Pelaez NM, Sevigny CP, Guyenet PG. 2001. Preproenkephalin mRNA is expressed by C1 and non-C1 barosensitive bulbospinal neurons in the rostral ventrolateral medulla of the rat. J Comp Neurol 435:111-126.
71. Stornetta RL, Sevigny CP, Guyenet PG. 2002a. Phrenic inspiratory pre-motor neurons are glutamatergic and enkephalinergic. submitted.
72. Stornetta RL, Sevigny CP, Guyenet PG. 2002b. Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several other groups of brainstem catecholaminergic neurons. J Comp Neurol 444:191-206.
73. Stornetta RL, Sevigny CP, Schreihofer AM, Rosin DL, Guyenet PG. 2002c. Vesicular glutamate transporter DNPI/GLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurons of the rat medulla. J Comp Neurol 444:207-220.
74. Sutcliffe JG, De Lecea L. 2000. The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding. J Neurosci Res 62:161-168.
75. Takamori S, Rhee JS, Rosenmund C, Jahn R. 2000. Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Nature 407:189-194.
76. Takamori S, Rhee JS, Rosenmund C, Jahn R. 2001. Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci 21: NIL7-NIL12.
77. 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 27:469-474.
78. Torrealba F, Yanagisawa M, and Saper CB. 2003. Colocalization of orexin a and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats. Neuroscience 119:1033-1044.
79. Van Bockstaele EJ, Saunders A, Commons KG, Liu XB, Peoples J. 2000. Evidence for coexistence of enkephalin and glutamate in axon terminals and cellular sites for functional interactions of their receptors in the rat locus coeruleus. J Comp Neurol 417:103-114.
80. Van den Pol AN. 1999. Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci 19:3171-3182.
81. Van den Pol AN, Gao XB, Obrietan K, Kilduff TS, Belousov AB. 1998. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. J Neurosci 18:7962-71.
82. I transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses. J Neurosci 22:142-155.
83. Weisskopf MG, Zalutsky RA, Nicoll RA. 1993. The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. Nature 362:423-427.
84. Willie JT, Chemelli RM, Sinton CM, Yanagisawa M. 2001. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci 24:429-458.