Brain Structure and Function

, Volume 220, Issue 1, pp 117–134 | Cite as

Distribution and neurochemical characterization of neurons in the rat ventrolateral medulla activated by glucoprivation

  • Lindsay M. Parker
  • Natasha N. Kumar
  • Tina Lonergan
  • Simon McMullan
  • Ann K. Goodchild
Original Article

Abstract

Hypoglycemia elicits physiological and behavioral responses which are mediated in part by neurons within the ventrolateral medulla (VLM). The present study describes the neurochemistry of neurons activated by glucoprivation (2-deoxy-d-glucose, 2DG), specifically those within regions containing the A1, caudal C1 (cC1) and rostral C1 (rC1) cell groups. 2DG induced c-Fos immunoreactivity throughout the VLM. Activated neurons expressing prepro-cocaine and amphetamine-regulated transcript (PPCART), neuropeptide Y (NPY), glutamic acid decarboxylase (GAD67) or prepro-enkephalin (PPE) mRNA and/or immunoreactivity (-ir) for tyrosine hydroxylase (TH) were identified. TH+ neurons were recruited in a dose-dependent manner. At high doses of 2DG [400 mg/kg, (n = 6)], 76 ± 1.2 % of activated neurons were TH+ representing 52 ± 1.3 % of the total TH population. Virtually all activated neurons in the A1 and cC1 regions but only 60 % in the rC1 region were TH+. Within the A1 region, TH+, TH+NPY+ and TH+NPY+PPE+ subpopulations were activated and likely regulate vasopressin, oxytocin, and corticotrophin releasing hormone (CRH) from the hypothalamus. Within the cC1 region, non-TH neurons, TH+NPY+, TH+NPY+PPCART+, and TH+NPY+PPE+ subpopulations were activated, likely regulating autonomic hypothalamic neurons or CRH and thyrotropin releasing hormone secretion. Within the rC1 region, non-TH neurons (40 % of those activated) were predominantly PPE+ and were recruited by higher 2DG doses. Of the TH+ activated neurons in the rC1 region, many expressed PPCART and half expressed NPY. The activated spinally projecting population was almost entirely TH+PPCART+ and is likely to regulate adrenaline and glucagon release. These data indicate that glucoprivation activates at least nine phenotypically distinct populations of neurons in the VLM.

Keywords

Glucoprivation RVLM C1 neurons A1 Bulbospinal Neurochemical coding 

Notes

Acknowledgments

The authors would like to thank Sophie Fletcher and Travis Wearne for their expert technical assistance and Dr Qun Li for design of the riboprobe sequence. This work was supported by the NHMRC (457068, APP1028183 and APP1030301), the ARC (DP120100920) and the National Heart Foundation (G09S4340), Hillcrest Foundation (Perpetual Trustees) and Macquarie University.

References

  1. Abbott SBG, Stornetta RL, Socolovsky CS, West GH, Guyenet PG (2009) Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary neurons increases sympathetic nerve activity and blood pressure in rats. J Physiol 587(23):5613–5631PubMedCentralPubMedGoogle Scholar
  2. Agassandian K, Shan Z, Raizada M, Sved AF, Card JP (2012) C1 catecholamine neurons form local circuit synaptic connections within the rostroventrolateral medulla of rat. Neuroscience 227:247–259PubMedCentralPubMedGoogle Scholar
  3. Amin A, Dhillo WS, Murphy KG (2011) The central effects of thyroid hormones on appetite. J Thyroid Res 2011:306510PubMedCentralPubMedGoogle Scholar
  4. Arvaniti K, Ricquier D, Champigny O, Richard D (1998) Leptin and corticosterone have opposite effects on food intake and the expression of UCP1 mRNA in brown adipose tissue of lep(ob)/lep(ob) mice. Endocrinology 139(9):4000–4003PubMedGoogle Scholar
  5. Baylis PH, Robertson GL (1980a) Rat vasopressin response to insulin-induced hypoglycemia. Endocrinology 107(6):1975–1979PubMedGoogle Scholar
  6. Baylis PH, Robertson GL (1980b) Vasopressin response to 2-deoxy-d-glucose in the rat. Endocrinology 107(6):1970–1974PubMedGoogle Scholar
  7. Baylis PH, Zerbe RL, Robertson GL (1981) Arginine vasopressin response to insulin-induced hypoglycemia in man. J Clin Endocrinol Metab 53(5):935–940PubMedGoogle Scholar
  8. Beall C, Ashford ML, McCrimmon RJ (2012) The physiology and pathophysiology of the neural control of the counterregulatory response. Am J Physiol Regul Integr Comp Physiol 302(2):R215–R223PubMedGoogle Scholar
  9. Beaulieu J, Champagne D, Drolet G (1996) Enkephalin innervation of the paraventricular nucleus of the hypothalamus: distribution of fibers and origins of input. J Chem Neuroanat 10(2):79–92PubMedGoogle Scholar
  10. Bobrovskaya L, Damanhuri HA, Ong LK, Schneider JJ, Dickson PW, Dunkley PR, Goodchild AK (2010) Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: an in vivo analysis. Neurochem Int 57(2):162–167PubMedGoogle Scholar
  11. Bowman BR, Kumar NN, Hassan SF, McMullan S, Goodchild AK (2013) Brain sources of inhibitory input to the rat rostral ventrolateral medulla. J Comp Neurol 521(1):213–232PubMedGoogle Scholar
  12. Breier A, Crane AM, Kennedy C, Sokoloff L (1993) The effects of pharmacologic doses of 2-deoxy-d-glucose on local cerebral blood flow in the awake, unrestrained rat. Brain Res 618:277–282PubMedGoogle Scholar
  13. Briski KP, Brandt JA (2000) Oxytocin and vasopressin neurones in principal and accessory hypothalamic magnocellular structures express fos-immunoreactivity in response to acute glucose deprivation. J Neuroendocrinol 12(5):409–414PubMedGoogle Scholar
  14. Burman KJ, Sartor DM, Verberne AJM, Llewellyn-Smith IJ (2004) Cocaine- and amphetamine-regulated transcript in catecholamine and noncatecholamine presympathetic vasomotor neurons of rat rostral ventrolateral medulla. J Comp Neurol 476(1):19–31PubMedGoogle Scholar
  15. Caraty A, Grino M, Locatelli A, Guillaume V, Boudouresque F, Conte-Devolx B, Oliver C (1990) Insulin-induced hypoglycemia stimulates corticotropin-releasing factor and arginine vasopressin secretion into hypophysial portal blood of conscious, unrestrained rams. J Clin Investig 85(6):1716–1721PubMedCentralPubMedGoogle Scholar
  16. Card JP, Sved JC, Craig B, Raizada M, Vazquez J, Sveb AF (2006) Efferent projections of rat rostroventrolateral medulla C1 catecholamine neurons: implications for the central control of cardiovascular regulation. J Comp Neurol 499(5):840–859PubMedGoogle Scholar
  17. Castonguay TW, Dallman MF, Stern JS (1986) Some metabolic and behavioral effects of adrenalectomy on obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 251(5):R923–R933Google Scholar
  18. Ceccatelli S, Millhorn DE, Hokfelt T, Goldstein M (1989) Evidence for the occurrence of an enkephalin-like peptide in adrenaline and noradrenaline neurons of the rat medulla oblongata. Exp Brain Res 74(3):631–640PubMedGoogle Scholar
  19. Cryer PE (2007) Hypoglycemia, functional brain failure, and brain death. J Clin Investig 117(4):868–870PubMedCentralPubMedGoogle Scholar
  20. Cunningham ET Jr, Sawchenko PE (1988) Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol 274(1):60–76PubMedGoogle Scholar
  21. Cunningham ET Jr, Bohn MC, Sawchenko PE (1990) Organization of adrenergic inputs to the paraventricular and supraoptic nuclei of the hypothalamus in the rat. J Comp Neurol 292(4):651–667PubMedGoogle Scholar
  22. Damanhuri HA, Burke PGR, Ong LK, Bobrovskaya L, Dickson PW, Dunkley PR, Goodchild AK (2012) Tyrosine hydroxylase phosphorylation in catecholaminergic brain regions: a marker of activation following acute hypotension and glucoprivation. PLoS One 7(11):e50535PubMedCentralPubMedGoogle Scholar
  23. Das M, Vihlen CS, Legradi G (2007) Hypothalamic and brainstem sources of pituitary adenylate cyclase-activating polypeptide nerve fibers innervating the hypothalamic paraventricular nucleus in the rat. J Comp Neurol 500(4):761–776PubMedCentralPubMedGoogle Scholar
  24. DePuy SD, Stornetta RL, Bochorishvili G, Deisseroth K, Witten I, Coates M, Guyenet PG (2013) Glutamatergic neurotransmission between the C1 neurons and the parasympathetic preganglionic neurons of the dorsal motor nucleus of the vagus. J Neurosci 33(4):1486–1497PubMedCentralPubMedGoogle Scholar
  25. DeRosa MA, Cryer PE (2004) Hypoglycemia and the sympathoadrenal system: Neurogenic symptoms are largely the result of sympathetic neural, rather than adrenomedullary, activation. Am J Physiol Endocrinol Metab 287(1 50-1):E32–E41PubMedGoogle Scholar
  26. Douglass J, McKinzie AA, Couceyro P (1995) PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J Neurosci 15(3 II):2471–2481PubMedGoogle Scholar
  27. Dragunow M, Faull R (1989) The use of c-fos as a metabolic marker in neuronal pathway tracing. J Neurosci Methods 29(3):261–265PubMedGoogle Scholar
  28. Drolet G, Van Bockstaele EJ, Aston-Jones G (1992) Robust enkephalin innervation of the locus coeruleus from the rostral medulla. J Neurosci 12(8):3162–3174PubMedGoogle Scholar
  29. Dun SL, Ng YK, Brailoiu GC, Ling EA, Dun NJ (2002) Cocaine- and amphetamine-regulated transcript peptide-immunoreactivity in adrenergic C1 neurons projecting to the intermediolateral cell column of the rat. J Chem Neuroanat 23(2):123–132PubMedGoogle Scholar
  30. Everitt BJ, Hokfelt T, Terenius L (1984) Differential co-existence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the rat. Neuroscience 11(2):443–462PubMedGoogle Scholar
  31. Farnham MMJ, Li Q, Goodchild AK, Pilowsky PM (2008) PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo. Am J Physiol Regul Integr Comp Physiol 294(4):R1304–R1311PubMedGoogle Scholar
  32. Fekete C, Wittmann G, Liposits Z, Lechan RM (2004) Origin of cocaine- and amphetamine-regulated transcript (CART)-immunoreactive innervation of the hypothalamic paraventricular nucleus. J Comp Neurol 469(3):340–350PubMedGoogle Scholar
  33. Furness JB, Morris JL, Gibbins IL, Costa M (1989) Chemical coding of neurons and plurichemical transmission. Annu Rev Pharmacol Toxicol 29:289–306PubMedGoogle Scholar
  34. Füzesi T, Wittmann G, Liposits Z, Lechan RM, Fekete C (2007) Contribution of noradrenergic and adrenergic cell groups of the brainstem and agouti-related protein-synthesizing neurons of the arcuate nucleus to neuropeptide-Y innervation of corticotropin-releasing hormone neurons in hypothalamic paraventricular nucleus of the rat. Endocrinology 148(11):5442–5450PubMedGoogle Scholar
  35. Gallego-Martin T, Fernandez-Martinez S, Rigual R, Obeso A, Gonzalez C (2012) Effects of low glucose on carotid body chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells. Am J Physiol Cell Physiol 302:C1128–C1140PubMedGoogle Scholar
  36. Gaszner B, Korosi A, Palkovits M, Roubos EW, Kozicz T (2007) Neuropeptide Y activates urocortin 1 neurons in the nonpreganglionic Edinger-Westphal nucleus. J Comp Neurol 500(4):708–719PubMedGoogle Scholar
  37. Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81(2):629–683PubMedGoogle Scholar
  38. Goodchild AK, Llewellyn-Smith IJ, Sun QJ, Chalmers J, Cunningham AM, Pilowsky PM (2000) Calbindin-immunoreactive neurons in the reticular formation of the rat brainstem: catecholamine content and spinal projections. J Comp Neurol 424(3):547–562PubMedGoogle Scholar
  39. Havel PJ, Parry SJ, Stern JS, Akpan JO, Gingerich RL, Taborsky GJ Jr, Curry DL (1994) Redundant parasympathetic and sympathoadrenal mediation of increased glucagon secretion during insulin-induced hypoglycemia in conscious rats. Metabolism 43(7):860–866PubMedGoogle Scholar
  40. He B, Douglas White B, Edwards GL, Martin RJ (1998) Neuropeptide Y antibody attenuates 2-deoxy-d-glucose induced feeding in rats. Brain Res 781(1–2):348–350PubMedGoogle Scholar
  41. Hevener AL, Bergman RN, Donovan CM (2001) Hypoglycemic detection does not occur in the hepatic artery or liver: findings consistent with a portal vein glucosensor locus. Diabetes 50:399–403PubMedGoogle Scholar
  42. Hillebrand JJG, De Wied D, Adan RAH (2002) Neuropeptides, food intake and body weight regulation: a hypothalamic focus. Peptides 23(12):2283–2306PubMedGoogle Scholar
  43. Johnson AD, Peoples J, Stornetta RL, Van Bockstaele EJ (2002) Opioid circuits originating from the nucleus paragigantocellularis and their potential role in opiate withdrawal. Brain Res 955(1–2):72–84PubMedGoogle Scholar
  44. Kotz CM, Grace MK, Briggs J, Levine AS, Billington CJ (1995) Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y- induced feeding and brown fat thermogenesis in the rat. Neural site of action. J Clin Investig 96(1):163–170PubMedCentralPubMedGoogle Scholar
  45. Kotz CM, Billington CJ, Levine AS (1997) Opioids in the nucleus of the solitary tract are involved in feeding in the rat. Am J Physiol Regul Integr Comp Physiol 272(4 41-4):R1028–R1032Google Scholar
  46. Koyama Y, Coker RH, Stone EE, Lacy DB, Jabbour K, Williams PE, Wasserman DH (2000) Evidence that carotid bodies play an important role in glucoregulation in vivo. Diabetes 49:1434–1442PubMedGoogle Scholar
  47. Kumar NN, Allen K, Parker L, Damanhuri H, Goodchild AK (2010) Neuropeptide coding of sympathetic preganglionic neurons; focus on adrenally projecting populations. Neuroscience 170(3):789–799PubMedGoogle Scholar
  48. Larhammar D, Ericsson A, Persson H (1987) Structure and expression of the rat neuropeptide Y gene. Proc Natl Acad Sci USA 84(7):2068–2072PubMedCentralPubMedGoogle Scholar
  49. Leibowitz SF, Sladek C, Spencer L, Tempel D (1988) Neuropeptide Y, epinephrine and norepinephrine in the paraventricular nucleus: stimulation of feeding and the release of corticosterone, vasopressin and glucose. Brain Res Bull 21(6):905–912PubMedGoogle Scholar
  50. Li AJ, Ritter S (2004) Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus. Eur J Neurosci 19(8):2147–2154PubMedGoogle Scholar
  51. Li Q, Goodchild AK, Seyedabadi M, Pilowsky PM (2005) Preprotachykinin A mRNA is colocalized with tyrosine hydroxylase- immunoreactivity in bulbospinal neurons. Neuroscience 136(1):205–216PubMedGoogle Scholar
  52. Li AJ, Wang Q, Ritter S (2006) Differential responsiveness of dopamine-β-hydroxylase gene expression to glucoprivation in different catecholamine cell groups. Endocrinology 147(7):3428–3434PubMedGoogle Scholar
  53. Li AJ, Wang Q, Dinh TT, Ritter S (2009) Simultaneous silencing of Npy and Dbh expression in hindbrain A1/C1 catecholamine cells suppresses glucoprivic feeding. J Neurosci 29(1):280–287PubMedCentralPubMedGoogle Scholar
  54. Liposits Z, Phelix C, Paull WK (1986) Adrenergic innervation of corticotropin releasing factor (CRF)—synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. A combined light and electron microscopic immunocytochemical study. Histochemistry 84(3):201–205PubMedGoogle Scholar
  55. Liposits Z, Paull WK, Jackson IMD, Lechan RM (1987) Hypophysiotrophic thyrotropin releasing hormone (TRH) synthesizing neurons. Ultrastructure, adrenergic innervation and putative transmitter action. Histochemistry 88(1):1–10PubMedGoogle Scholar
  56. Lipski J, Kanjhan R, Kruszewska B, Smith M (1995) Barosensitive neurons in the rostral ventrolateral medulla of the rat in vivo: morphological properties and relationship to C1 adrenergic neurons. Neuroscience 69(2):601–618PubMedGoogle Scholar
  57. Madden CJ, Stocker SD, Sved AF (2006) Attenuation of homeostatic responses to hypotension and glucoprivation after destruction of catecholaminergic rostral ventrolateral medulla neurons. Am J Physiol Regul Integr Comp Physiol 291(3):R751–R759PubMedGoogle Scholar
  58. Medvedev OS, Esler MD, Angus JA, Cox HS, Eisenhofer G (1990) Simultaneous determination of plasma noradrenaline and adrenaline kinetics. Responses to nitroprusside-induced hypotension and 2-deoxyglucose-induced glucopenia in the rabbit. Naunyn Schmiedebergs Arch Pharmacol 341(3):192–199PubMedGoogle Scholar
  59. Michelsen BK, Petersen JS, Boel E, Moldrup A, Dyrberg T, Madsen OD (1991) Cloning, characterization, and autoimmune recognition of rat islet glutamic acid decarboxylase in insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 88(19):8754–8758PubMedCentralPubMedGoogle Scholar
  60. Millhorn DE, Seroogy K, Hokfelt T, Schmued LC, Terenius L, Buchan A, Brown JC (1987) Neurons of the ventral medulla oblongata that contain both somatostatin and enkephalin immunoreactivities project to nucleus tractus solitarii and spinal cord. Brain Res 424(1):99–108PubMedGoogle Scholar
  61. Minson JB, Llewellyn-Smith IJ, Pilowsky PM, Chalmers JP (1994) Bulbospinal neuropeptide Y-immunoreactive neurons in the rat: comparison with adrenaline-synthesising neurons. J Auton Nerv Syst 47(3):233–243PubMedGoogle Scholar
  62. Morrison SF, Nakamura K, Madden CJ (2008) Central control of thermogenesis in mammals. Exp Physiol 93(7):773–797PubMedCentralPubMedGoogle Scholar
  63. Murakami S, Okamura H, Pelletier G, Ibata Y (1989) Differential colocalization of neuropeptide Y- and methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactivity in catecholaminergic neurons in the rat brain stem. J Comp Neurol 281(4):532–544PubMedGoogle Scholar
  64. Parker LM, Kumar NN, Lonergan T, Goodchild AK (2013) Neurochemical codes of sympathetic preganglionic neurons activated by glucoprivation. J Comp Neurol. doi: 10.1002/cne.23310 PubMedGoogle Scholar
  65. Petrov T, Krukoff TL, Jhamandas JH (1993) Branching projections of catecholaminergic brainstem neurons to the paraventricular hypothalamic nucleus and the central nucleus of the amygdala in the rat. Brain Res 609(1–2):81–92PubMedGoogle Scholar
  66. Phillips JK, Goodchild AK, Dubey R, Sesiashvili E, Takeda M, Chalmers J, Pilowsky PM, Lipski J (2001) Differential expression of catecholamine biosynthetic enzymes in the rat ventrolateral medulla. J Comp Neurol 432(1):20–34PubMedGoogle Scholar
  67. Plotsky PM, Bruhn TO, Vale W (1985) Hypophysiotropic regulation of adrenocorticotropin secretion in response to insulin-induced hypoglycemia. Endocrinology 117(1):323–329PubMedGoogle Scholar
  68. Pretel S, Piekut DT (1991) ACTH and enkephalin axonal input to paraventricular neurons containing c-fos-like immunoreactivity. Synapse 8(2):100–106PubMedGoogle Scholar
  69. Ritter RC, Slusser PG, Stone S (1981) Glucoreceptors controlling feeding and blood glucose: location in the hindbrain. Science 213(4506):451–453PubMedGoogle Scholar
  70. Ritter S, Scheurink A, Singer LK (1995) 2-Deoxy-d-glucose but not 2-mercaptoacetate increases Fos-like immunoreactivity in adrenal medulla and sympathetic preganglionic neurons. Obes Res 3(Suppl 5):729S–734SPubMedGoogle Scholar
  71. Ritter S, Llewellyn-Smith I, Dinh TT (1998) Subgroups of hindbrain catecholamine neurons are selectively activated by 2-deoxy-d-glucose induced metabolic challenge. Brain Res 805(1–2):41–54PubMedGoogle Scholar
  72. Ritter S, Dinh TT, Zhang Y (2000) Localization of hindbrain glucoreceptive sites controlling food intake and blood glucose. Brain Res 856(1–2):37–47PubMedGoogle Scholar
  73. Ritter S, Bugarith K, Dinh TT (2001) Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation. J Comp Neurol 432(2):197–216PubMedGoogle Scholar
  74. Ritter S, Dinh TT, Li AJ (2006) Hindbrain catecholamine neurons control multiple glucoregulatory responses. Physiol Behav 89(4):490–500PubMedGoogle Scholar
  75. Ritter S, Li AJ, Wang Q, Dinh TT (2011) Minireview: the value of looking backward: The essential role of the hindbrain in counterregulatory responses to glucose deficit. Endocrinology 152(11):4019–4032PubMedCentralPubMedGoogle Scholar
  76. Rizza RA, Mandarino LJ, Gerich JE (1982) Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 54(1):131–138PubMedGoogle Scholar
  77. Ross CA, Ruggiero DA, Joh TH, Park DH, Reis DJ (1983) Adrenaline synthesizing neurons in the rostral ventrolateral medulla: a possible role in tonic vasomotor control. Brain Res 273:356–361PubMedGoogle Scholar
  78. Ross CA, Ruggiero DA, Joh TH (1984) Rostral ventrolateral medulla: selective projections to the thoracic autonomic cell column from the region containing C1 adrenaline neurons. J Comp Neurol 228(2):168–185PubMedGoogle Scholar
  79. Sacca L, Perez G, Carteni G, Rengo F (1977) Evaluation of the role of the sympathetic nervous system in the glucoregulatory response to insulin-induced hypoglycemia in the rat. Endocrinology 101(4):1016–1022PubMedGoogle Scholar
  80. Sawchenko PE, Swanson LW (1982) The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res 257(3):275–325PubMedGoogle Scholar
  81. Sawchenko PE, Swanson LW, Grzanna R (1985) Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol 241(2):138–153PubMedGoogle Scholar
  82. Schreihofer AM, Guyenet PG (1997) Identification of C1 presympathetic neurons in rat rostral ventrolateral medulla by juxtacellular labeling in vivo. J Comp Neurol 387(4):524–536PubMedGoogle Scholar
  83. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404(6778):661–671PubMedGoogle Scholar
  84. Sindelar DK, Ste Marie L, Miura GI, Palmiter RD, McMinn JE, Morton GJ, Schwartz MW (2004) Neuropeptide Y is required for hyperphagic feeding in response to neuroglucopenia. Endocrinology 145(7):3363–3368PubMedGoogle Scholar
  85. Smith SM, Vaughan JM, Donaldson CJ, Rivier J, Li C, Chen A, Vale WW (2004) Cocaine- and amphetamine-regulated transcript activates the hypothalamic-pituitary-adrenal axis through a corticotropin-releasing factor receptor-dependent mechanism. Endocrinology 145(11):5202–5209PubMedGoogle Scholar
  86. Spirovski D, Li Q, Pilowsky PM (2012) Brainstem galanin-synthesizing neurons are differentially activated by chemoreceptor stimuli and represent a subpopulation of respiratory neurons. J Comp Neurol 520(1):154–173PubMedGoogle Scholar
  87. Ste Marie L, Palmiter RD (2003) Norepinephrine and epinephrine-deficient mice are hyperinsulinemic and have lower blood glucose. Endocrinology 144(10):4427–4432PubMedGoogle Scholar
  88. Stornetta RL (2009) Neurochemistry of bulbospinal presympathetic neurons of the medulla oblongata. J Chem Neuroanat 38(3):222–230PubMedCentralPubMedGoogle Scholar
  89. 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(3):367–380PubMedGoogle Scholar
  90. Stornetta RL, Akey PJ, Guyenet PG (1999) Location and electrophysiological characterization of rostral medullary adrenergic neurons that contain neuropeptide Y mRNA in rat medulla. J Comp Neurol 415(4):482–500PubMedGoogle Scholar
  91. 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(1):111–126PubMedGoogle Scholar
  92. Stornetta RL, Sevigny CP, Guyenet PG (2002) Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several other groups of brainstem catecholaminergic neurons. J Comp Neurol 444(3):191–206PubMedGoogle Scholar
  93. Swanson LW, Sawchenko PE, Berod A, Hartman BK, Helle KB, Vanorden DE (1981) An immunohistochemical study of the organization of catecholaminergic cells and terminal fields in the paraventricular and supraoptic nuclei of the hypothalamus. J Comp Neurol 196(2):271–285PubMedGoogle Scholar
  94. Swanson DJ, Zellmer E, Lewis EJ (1998) AP1 proteins mediate the cAMP response of the dopamine beta-hydroxylase gene. J Biol Chem 273(37):24065–24074PubMedGoogle Scholar
  95. Taborsky GJ, Ahren B, Havel PJ (1998) Autonomic mediation of glucagon secretion during hypoglycemia. Diabetes 47:995–1005PubMedGoogle Scholar
  96. Tiesjema B, Adan RAH, Luijendijk MCM, Kalsbeek A, La Fleur SE (2007) Differential effects of recombinant adeno-associated virus-mediated neuropeptide Y overexpression in the hypothalamic paraventricular nucleus and lateral hypothalamus on feeding behavior. J Neurosci 27(51):14139–14146PubMedGoogle Scholar
  97. Tseng CJ, Lin HC, Wang SD, Tung CS (1993) Immunohistochemical study of catecholamine enzymes and neuropeptide Y (NPY) in the rostral ventrolateral medulla and bulbospinal projection. J Comp Neurol 334(2):294–303PubMedGoogle Scholar
  98. Tucker DC, Saper CB, Ruggiero DA, Reis DJ (1987) Organization of central adrenergic pathways: i. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord. J Comp Neurol 259(4):591–603PubMedGoogle Scholar
  99. Verberne AJM, Sartor DM (2010) Rostroventrolateral medullary neurons modulate glucose homeostasis in the rat. Am J Physiol Endocrinol Metab 299(5):E802–E807PubMedGoogle Scholar
  100. Vollmer RR, Balcita JJ, Sved AF, Edwards DJ (1997) Adrenal epinephrine and norepinephrine release to hypoglycemia measured by microdialysis in conscious rats. Am J Physiol Regul Integr Comp Physiol 273(5 42-5):R1758–R1763Google Scholar
  101. Wittmann G (2008) Regulation of hypophysiotrophic corticotrophin-releasing hormone- and thyrotrophin-releasing hormone-synthesising neurones by brainstem catecholaminergic neurones. J Neuroendocrinol 20(7):952–960PubMedGoogle Scholar
  102. Wittmann G, Liposits Z, Lechan RM, Fekete C (2002) Medullary adrenergic neurons contribute to the neuropeptide Y-ergic innervation of hypophysiotropic thyrotropin-releasing hormone-synthesizing neurons in the rat. Neurosci Lett 324(1):69–73PubMedGoogle Scholar
  103. Wittmann G, Liposits Z, Lechan RM, Fekete C (2004) () Medullary adrenergic neurons contribute to the cocaine- and amphetamine-regulated transcript-immunoreactive innervation of thyrotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus. Brain Res 1006(1):1–7PubMedGoogle Scholar
  104. Wittmann G, Liposits Z, Lechan RM, Fekete C (2005) Origin of cocaine- and amphetamine-regulated transcript-containing axons innervating hypophysiotropic corticotropin-releasing hormone-synthesizing neurons in the rat. Endocrinology 146(7):2985–2991PubMedGoogle Scholar
  105. Wittmann G, Füzesi T, Singru PS, Liposits Z, Lechan RM, Fekete C (2009) Efferent projections of thyrotropin-releasing hormone-synthesizing neurons residing in the anterior parvocellular subdivision of the hypothalamic paraventricular nucleus. J Comp Neurol 515(3):313–330PubMedCentralPubMedGoogle Scholar
  106. Woulfe JM, Flumerfelt BA, Hrycyshyn AW (1990) Efferent connections of the A1 noradrenergic cell group: a DBH immunohistochemical and PHA-L anterograde tracing study. Exp Neurol 109(3):308–322PubMedGoogle Scholar
  107. Yamaguchi N (1992) Sympathoadrenal system in neuroendocrine control of glucose: mechanisms involved in the liver, pancreas, and adrenal gland under hemorrhagic and hypoglycemic stress. Can J Physiol Pharmacol 70(2):167–206PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Lindsay M. Parker
    • 1
  • Natasha N. Kumar
    • 1
  • Tina Lonergan
    • 1
  • Simon McMullan
    • 1
  • Ann K. Goodchild
    • 1
  1. 1.The Australian School of Advanced MedicineMacquarie UniversityNorth Ryde, SydneyAustralia

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