Role of Astrocytes in Central Respiratory Chemoreception

  • Jaime Eugenín LeónEmail author
  • María José Olivares
  • Sebastián Beltrán-Castillo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 949)


Astrocytes perform various homeostatic functions in the nervous system beyond that of a supportive or metabolic role for neurons. A growing body of evidence indicates that astrocytes are crucial for central respiratory chemoreception. This review presents a classical overview of respiratory central chemoreception and the new evidence for astrocytes as brainstem sensors in the respiratory response to hypercapnia. We review properties of astrocytes for chemosensory function and for modulation of the respiratory network. We propose that astrocytes not only mediate between CO2/H+ levels and motor responses, but they also allow for two emergent functions: (1) Amplifying the responses of intrinsic chemosensitive neurons through feedforward signaling via gliotransmitters and; (2) Recruiting non-intrinsically chemosensitive cells thanks to volume spreading of signals (calcium waves and gliotransmitters) to regions distant from the CO2/H+ sensitive domains. Thus, astrocytes may both increase the intensity of the neuron responses at the chemosensitive sites and recruit of a greater number of respiratory neurons to participate in the response to hypercapnia.


Respiratory rhythm Central chemoreception Raphe nuclei Locus coeruleus nuclei Retrotrapezoid nuclei Brainstem Glia Gliotransmitters Astrocytes 



5-hydroxytryptamine (Serotonin)




Artificial cerebrospinal fluid


α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor


Atrial natriuretic peptide


Adenosine triphosphate


Carbonic anhydrase enzyme


Central congenital hypoventilation syndrome


Central nervous system




Carbon dioxide


6-cyano-7-nitroquinoxaline-2,3-dione—competitive AMPA/kainate receptor antagonist


Caudal nucleus tractus solitarius


Cerebrospinal fluid


Caudal ventrolateral medulla


Caudal ventral respiratory group




Dorsal respiratory columns


Excitatory postsynaptic potentials


γ-aminobutyric acid


Glial fibrillary acidic protein


Pontine Kölliker-Fuse nucleus


Knock out


Locus coeruleus


Laterodorsal tegmental nucleus


Lateral parabrachial nucleus


Long-term potentiation


Medial portion of the rostral ventrolateral medulla


Methionine sulfoximine


Neurokinin 1 receptor




N-methyl-D-aspartate receptor


Nitric oxide


Nucleus tractus solitarius


Partial arterial pressure of carbon dioxide


Partial pressure of carbon dioxide


Partial arterial pressure of oxygen


Perifornical-lateral hypothalamic area


Peripheral nervous system




Pedunculopontine tegmental nucleus


PreBötzinger Complex




Prepro-orexin knockout mice


Medullary raphe nucleus


Respiratory pattern generator


Retrotrapezoid/parafacial respiratory group


Nucleus reticularis rostroventrolateralis


Rostral ventrolateral medulla


Rostral ventral respiratory group


Serotonin transporter


Sudden infant death syndrome


Substance P


Saporin–substance P conjugate


Tyrosine hydroxylase


Total internal reflection fluorescence


Thyrotropin releasing hormone


Channels Transient receptor potential channels


Tractus solitaries-evoked excitatory postsynaptic currents


Ventrolateral medullary surface


Ventral medullary surface


Ventral respiratory columns


Ventral respiratory group



Support from Grants Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) #1130874 (JE), Comisión Nacional de Ciencia y Tecnología (CONICYT) #21140669 (MJ Olivares), Comisión Nacional de Ciencia y Tecnología (CONICYT) #21120594 (S Beltrán-Castillo). DICYT-USACH (JE).


  1. Abbott SB, Stornetta RL, Fortuna MG, Depuy SD, West GH, Harris TE, Guyenet PG (2009) Photostimulation of retrotrapezoid nucleus phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats. J Neurosci 29(18):5806–5819. doi: 10.1523/JNEUROSCI.1106-09.2009 PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abbott SB, Stornetta RL, Coates MB, Guyenet PG (2011) Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats. J Neurosci 31(45):16410–16422. doi: 10.1523/JNEUROSCI.3280-11.2011 PubMedPubMedCentralCrossRefGoogle Scholar
  3. Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32(1):19–29. doi: 10.1016/j.tins.2008.10.001 PubMedCrossRefGoogle Scholar
  4. Accorsi-Mendonca D, Zoccal DB, Bonagamba LG, Machado BH (2013) Glial cells modulate the synaptic transmission of NTS neurons sending projections to ventral medulla of Wistar rats. Physiol Rep 1(4):e00080. doi: 10.1002/phy2.80 PubMedPubMedCentralCrossRefGoogle Scholar
  5. Akilesh MR, Kamper M, Li A, Nattie EE (1997) Effects of unilateral lesions of retrotrapezoid nucleus on breathing in awake rats. J Appl Physiol 82(2):469–479PubMedGoogle Scholar
  6. Albrecht J, Simmons M, Dutton GR, Norenberg MD (1991) Aluminum chloride stimulates the release of endogenous glutamate, taurine and adenosine from cultured rat cortical astrocytes. Neurosci Lett 127(1):105–107PubMedCrossRefGoogle Scholar
  7. Alexandre C, Andermann ML, Scammell TE (2013) Control of arousal by the orexin neurons. Curr Opin Neurobiol 23(5):752–759. doi: 10.1016/j.conb.2013.04.008 PubMedPubMedCentralCrossRefGoogle Scholar
  8. Amiel J, Laudier B, Attie-Bitach T, Trang H, de Pontual L, Gener B, Trochet D, Etchevers H, Ray P, Simonneau M, Vekemans M, Munnich A, Gaultier C, Lyonnet S (2003) Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet 33(4):459–461. doi: 10.1038/ng1130 PubMedCrossRefGoogle Scholar
  9. Amiel J, Dubreuil V, Ramanantsoa N, Fortin G, Gallego J, Brunet JF, Goridis C (2009) PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models. Respir Physiol Neurobiol 168(1–2):125–132. doi: 10.1016/j.resp.2009.03.005 PubMedCrossRefGoogle Scholar
  10. Antunes VR, Braga VA, Machado BH (2005) Autonomic and respiratory responses to microinjection of ATP into the intermediate or caudal nucleus tractus solitarius in the working heart-brainstem preparation of the rat. Clin Exp Pharmacol Physiol 32:467–472PubMedCrossRefGoogle Scholar
  11. Araque A, Martin ED, Perea G, Arellano JI, Buno W (2002) Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices. J Neurosci 22(7):2443–2450PubMedGoogle Scholar
  12. Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A (2014) Gliotransmitters travel in time and space. Neuron 81(4):728–739. doi: 10.1016/j.neuron.2014.02.007 PubMedPubMedCentralCrossRefGoogle Scholar
  13. Armstrong DM, Rotler A, Hersh LB, Pickel VM (1988) Localization of choline acetyltransferase in perikarya and dendrites within the nuclei of the solitary tracts. J Neurosci Res 20(3):279–290. doi: 10.1002/jnr.490200302 PubMedCrossRefGoogle Scholar
  14. Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA (2010) Glial and neuronal control of brain blood flow. Nature 468(7321):232–243. doi: 10.1038/nature09613 PubMedPubMedCentralCrossRefGoogle Scholar
  15. Baird NR, Orlowski J, Szabó EZ, Zaun HC, Schultheis PJ, Menon AG, Shull GE (1999) Molecular cloning, genomic organization, and functional expression of Na+/H+ exchanger isoform 5 (NHE5) from human brain. J Biol Chem 274(7):4377–4382PubMedCrossRefGoogle Scholar
  16. Ballantyne D, Scheid P (2001) Central respiratory chemosensitivity: cellular and network mechanisms. Adv Exp Med Biol 499:17–26PubMedCrossRefGoogle Scholar
  17. Ballanyi K, Panaitescu B, Ruangkittisakul A (2010) Control of breathing by “nerve glue”. Sci Signal 3(147):e41. doi: 10.1126/scisignal.3147pe41 CrossRefGoogle Scholar
  18. Belanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724–738. doi: 10.1016/j.cmet.2011.08.016 PubMedCrossRefGoogle Scholar
  19. Belegu R, Hadziefendic S, Dreshaj IA, Haxhiu MA, Martin RJ (1999) CO2-induced c-fos expression in medullary neurons during early development. Respir Physiol 117(1):13–28PubMedCrossRefGoogle Scholar
  20. Ben Achour S, Pascual O (2010) Glia: the many ways to modulate synaptic plasticity. Neurochem Int 57(4):440–445. doi: 10.1016/j.neuint.2010.02.013 PubMedCrossRefGoogle Scholar
  21. Berger AJ, Cooney KA (1982) Ventilatory effects of kainic acid injection of the ventrolateral solitary nucleus. J Appl Physiol 52:131–140PubMedGoogle Scholar
  22. Biancardi V, Bicego KC, Almeida MC, Gargaglioni LH (2008) Locus coeruleus noradrenergic neurons and CO2 drive to breathing. Pflugers Arch 455(6):1119–1128. doi: 10.1007/s00424-007-0338-8 PubMedCrossRefGoogle Scholar
  23. Boscan P, Pickering AE, Paton JFR (2002) The nucleus of the solitary tract: an integrating station for nociceptive and cardiorespiratory afferents. Exp Physiol 87(2):259–266PubMedCrossRefGoogle Scholar
  24. Boudinot E, Yamada M, Wess J, Champagnat J, Foutz AS (2004) Ventilatory pattern and chemosensitivity in M1 and M3 muscarinic receptor knockout mice. Respir Physiol Neurobiol 139(3):237–245. doi: 10.1016/j.resp.2003.10.006 PubMedCrossRefGoogle Scholar
  25. Boudinot E, Champagnat J, Foutz AS (2008) M(1)/M(3) and M(2)/M(4) muscarinic receptor double-knockout mice present distinct respiratory phenotypes. Respir Physiol Neurobiol 161(1):54–61. doi: 10.1016/j.resp.2007.12.001 PubMedCrossRefGoogle Scholar
  26. Bowery NG, Brown DA, Collins GG, Galvan M, Marsh S, Yamini G (1976) Indirect effects of amino-acids on sympathetic ganglion cells mediated through the release of gamma-aminobutyric acid from glial cells. Br J Pharmacol 57(1):73–91PubMedPubMedCentralCrossRefGoogle Scholar
  27. Braga VA, Soriano RN, Braccialli AL, de Paula PM, Bonagamba LG, Paton JF, Machado BH (2007) Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation. J Physiol 581(Pt 3):1129–1145. doi: 10.1113/jphysiol.2007.129031 PubMedPubMedCentralCrossRefGoogle Scholar
  28. Brookes N (1997) Intracellullar pH as a regulatory signal in astrocyte metabolism. Glia 21:64–73PubMedCrossRefGoogle Scholar
  29. Brunet JF, Pattyn A (2002) Phox2 genes—from patterning to connectivity. Curr Opin Genet Dev 12(4):435–440PubMedCrossRefGoogle Scholar
  30. Brust RD, Corcoran AE, Richerson GB, Nattie E, Dymecki SM (2014) Functional and developmental identification of a molecular subtype of brain serotonergic neuron specialized to regulate breathing dynamics. Cell Rep 9(6):2152–2165. doi: 10.1016/j.celrep.2014.11.027 PubMedPubMedCentralCrossRefGoogle Scholar
  31. Burke PG, Kanbar R, Viar KE, Stornetta RL, Guyenet PG (2015) Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs. J Appl Physiol 118(12):1491–1501. doi: 10.1152/japplphysiol.00164.2015 (1985)PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cao Y, Song G (2007) Purinergic modulation of respiration via medullary raphe nuclei in rats. Respir Physiol Neurobiol 155(2):114–120. doi: 10.1016/j.resp.2006.04.013 PubMedCrossRefGoogle Scholar
  33. Caravagna C, Soliz J, Seaborn T (2013) Brain-derived neurotrophic factor interacts with astrocytes and neurons to control respiration. Eur J Neurosci 38(9):3261–3269. doi: 10.1111/ejn.12320 PubMedCrossRefGoogle Scholar
  34. Carmignoto G, Pasti L, Pozzan T (1998) On the role of voltage-dependent calcium channels in calcium signaling of astrocytes in situ. J Neurosci 18(12):4637–4645PubMedGoogle Scholar
  35. Chen X, Wang L, Zhou Y, Zheng LH, Zhou Z (2005) “Kiss-and-run” glutamate secretion in cultured and freshly isolated rat hippocampal astrocytes. J Neurosci 25(40):9236–9243. doi: 10.1523/JNEUROSCI.1640-05.2005 PubMedCrossRefGoogle Scholar
  36. Coates EL, Li A, Nattie EE (1993) Widespread sites of brain stem ventilatory chemoreceptors. J Appl Physiol 75(1):5–14PubMedGoogle Scholar
  37. Coddou C, Bravo E, Eugenin J (2009) Alterations in cholinergic sensitivity of respiratory neurons induced by pre-natal nicotine: a mechanism for respiratory dysfunction in neonatal mice. Philos Trans R Soc Lond 364(1529):2527–2535CrossRefGoogle Scholar
  38. Connelly CA, Otto-Smith MR, Feldman JL (1992) Blockade of NMDA receptor-channels by MK-801 alters breathing in adult rats. Brain Res 596(1–2):99–110PubMedCrossRefGoogle Scholar
  39. Constam DB, Philipp J, Malipiero UV, ten Dijke P, Schachner M, Fontana A (1992) Differential expression of transforming growth factor-beta 1,—beta 2, and—beta 3 by glioblastoma cells, astrocytes, and microglia. J Immunol 148(5):1404–1410PubMedGoogle Scholar
  40. Corcoran AE, Richerson GB, Harris MB (2013) Serotonergic mechanisms are necessary for central respiratory chemoresponsiveness in situ. Respir Physiol Neurobiol 186(2):214–220. doi: 10.1016/j.resp.2013.02.015 PubMedPubMedCentralCrossRefGoogle Scholar
  41. Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247(4941):470–473PubMedCrossRefGoogle Scholar
  42. Corsini E, Dufour A, Ciusani E, Gelati M, Frigerio S, Gritti A, Cajola L, Mancardi GL, Massa G, Salmaggi A (1996) Human brain endothelial cells and astrocytes produce IL-1 beta but not IL-10. Scand J Immunol 44(5):506–511PubMedCrossRefGoogle Scholar
  43. Cui N, Zhang X, Tapedalli JS, Yu L, Gai H, Petit J, Pamulapati RT, Jin X, Jiang C (2011) Involvement of TRP channels in the CO2 chemosensitivity of locus coeruleus neurons. J Neurophysiol 105:2791–2801. doi: 10.1152/jn.00759.2010.-Catecholaminergic PubMedPubMedCentralCrossRefGoogle Scholar
  44. Curran AK, Darnall RA, Filiano JJ, Li A, Nattie EE (2001) Muscimol dialysis in the rostral ventral medulla reduced the CO(2) response in awake and sleeping piglets. J Appl Physiol 90(3):971–980PubMedGoogle Scholar
  45. da Silva GS, Li A, Nattie E (2010) High CO2/H+ dialysis in the caudal ventrolateral medulla (Loeschcke’s area) increases ventilation in wakefulness. Respir Physiol Neurobiol 171(1):46–53. doi: 10.1016/j.resp.2010.01.014 PubMedPubMedCentralCrossRefGoogle Scholar
  46. da Silva GS, Giusti H, Benedetti M, Dias MB, Gargaglioni LH, Branco LG, Glass ML (2011) Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia. Pflugers Arch 462(3):407–418. doi: 10.1007/s00424-011-0990-x PubMedCrossRefGoogle Scholar
  47. da Silva GS, Moraes DJ, Giusti H, Dias MB, Glass ML (2012) Purinergic transmission in the rostral but not caudal medullary raphe contributes to the hypercapnia-induced ventilatory response in unanesthetized rats. Respir Physiol Neurobiol 184(1):41–47. doi: 10.1016/j.resp.2012.07.015 PubMedCrossRefGoogle Scholar
  48. De Paula PM, Antunes VR, Bonagamba LG, Machado BH (2004) Cardiovascular responses to microinjection of ATP into the nucleus tractus solitarii of awake rats. Am J Physiol 287:R1164–R1171. doi: 10.1152/ajpregu.00722.2003 Google Scholar
  49. Dean JB, Bayliss DA, Erickson JT, Lawing WL, Millhorn DE (1990) Depolarization and stimulation of neurons in nucleus tractus solitarii by carbon dioxide does not require chemical synaptic input. Neuroscience 36(1):207–216PubMedCrossRefGoogle Scholar
  50. Deitmer JW, Rose CR (1996) pH regulation and proton signalling by glial cells. Prog Neurobiol 48(2):73–103PubMedCrossRefGoogle Scholar
  51. Deng BS, Nakamura A, Zhang W, Yanagisawa M, Fukuda Y, Kuwaki T (2007) Contribution of orexin in hypercapnic chemoreflex: evidence from genetic and pharmacological disruption and supplementation studies in mice. J Appl Physiol 103(5):1772–1779. doi: 10.1152/japplphysiol.00075.2007 (1985)PubMedCrossRefGoogle Scholar
  52. Dev NB, Loeschcke HH (1979a) A cholinergic mechanism involved in the respiratory chemosensitivity. Pflügers Arch 379:29–36PubMedCrossRefGoogle Scholar
  53. Dev NB, Loeschcke HH (1979b) Topography of the respiratory and circulatory responses to acetylcholine and nicotine on the ventral surface of the medulla oblongata. Pflügers Arch 379:19–27PubMedCrossRefGoogle Scholar
  54. Dias MB, Nucci TB, Margatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG (2007) Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol 103(5):1780–1788PubMedCrossRefGoogle Scholar
  55. Dias MB, Li A, Nattie E (2008) Focal CO2 dialysis in raphe obscurus does not stimulate ventilation but enhances the response to focal CO2 dialysis in the retrotrapezoid nucleus. J Appl Physiol 105(1):83–90PubMedPubMedCentralCrossRefGoogle Scholar
  56. Dias MB, Li A, Nattie EE (2009) Antagonism of orexin receptor-1 in the retrotrapezoid nucleus inhibits the ventilatory response to hypercapnia predominantly in wakefulness. J Physiol 587(Pt 9):2059–2067. doi: 10.1113/jphysiol.2008.168260 PubMedPubMedCentralCrossRefGoogle Scholar
  57. Dias MB, Li A, Nattie E (2010) The orexin receptor 1 (OX1R) in the rostral medullary raphe contributes to the hypercapnic chemoreflex in wakefulness, during the active period of the diurnal cycle. Respir Physiol Neurobiol 170(1):96–102. doi: 10.1016/j.resp.2009.12.002 PubMedCrossRefGoogle Scholar
  58. Dreshaj IA, Haxhiu MA, Martin RJ (1998) Role of the medullary raphe nuclei in the respiratory response to CO2. Respir Physiol 111(1):15–23PubMedCrossRefGoogle Scholar
  59. Dubreuil V, Ramanantsoa N, Trochet D, Vaubourg V, Amiel J, Gallego J, Brunet JF, Goridis C (2008) A human mutation in phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons. Proc Natl Acad Sci USA 105(3):1069–1072. doi: 10.1073/pnas.0709115105 CrossRefGoogle Scholar
  60. Dubreuil V, Barhanin J, Goridis C, Brunet JF (2009a) Breathing with Phox2b. Philos Trans R Soc Lond 364:2477–2483. doi: 10.1098/rstb.2009.0085 CrossRefGoogle Scholar
  61. Dubreuil V, Thoby-Brisson M, Rallu M, Persson K, Pattyn A, Birchmeier C, Brunet JF, Fortin G, Goridis C (2009b) Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons. J Neurosci 29(47):14836–14846. doi: 10.1523/JNEUROSCI.2623-09.2009 PubMedCrossRefGoogle Scholar
  62. Dutschmann M, Kron M, Morschel M, Gestreau C (2007) Activation of Orexin B receptors in the pontine Kolliker-Fuse nucleus modulates pre-inspiratory hypoglossal motor activity in rat. Respir Physiol Neurobiol 159(2):232–235PubMedCrossRefGoogle Scholar
  63. Erlichman JS, Leiter JC (2010) Glia modulation of the extracellular milieu as a factor in central CO2 chemosensitivity and respiratory control. J Appl Physiol 108:1803–1811. doi: 10.1152/japplphysiol.01321.2009.-We PubMedPubMedCentralCrossRefGoogle Scholar
  64. Erlichman JS, Li A, Nattie EE (1998) Ventilatory effects of glial dysfunction in a rat brain stem chemoreceptor region. J Appl Physiol 85(5):1599–1604PubMedGoogle Scholar
  65. Erlichman JS, Leiter JC, Gourine AV (2010) ATP, glia and central respiratory control. Respir Physiol Neurobiol 173(3):305–311. doi: 10.1016/j.resp.2010.06.009 PubMedPubMedCentralCrossRefGoogle Scholar
  66. Eugenin J (1995) Generation of the respiratory rhythm: modelling the inspiratory off switch as a neural integrator. J Theor Biol 172(2):107–120PubMedCrossRefGoogle Scholar
  67. Eugenin J, Nicholls JG (1997) Chemosensory and cholinergic stimulation of fictive respiration in isolated CNS of neonatal opossum. J Physiol (London) 501(Pt 2):425–437CrossRefGoogle Scholar
  68. Eugenin J, von Bernhardi R, Muller KJ, Llona I (2006) Development and pH sensitivity of the respiratory rhythm of fetal mice in vitro. Neuroscience 141(1):223–231PubMedCrossRefGoogle Scholar
  69. Eugenin J, Otarola M, Bravo E, Coddou C, Cerpa V, Reyes-Parada M, Llona I, von Bernhardi R (2008) Prenatal to early postnatal nicotine exposure impairs central chemoreception and modifies breathing pattern in mouse neonates: a probable link to sudden infant death syndrome. J Neurosci 28(51):13907–13917PubMedCrossRefGoogle Scholar
  70. Eyzaguirre C, Fitzgerald RS, Lahiri S, Zapata P (1983) Arterial chemoreceptors. In: Shepherd JT, Abboud FM (eds) American physiological society: handbook of physiology, vol 3., The Cardiovascular SystemWilliams & Wilkins Co., Baltimore, Maryland, pp 557–621Google Scholar
  71. Feldman JL (1986) Neurophysiology of breathing in mammals. In: Bloom FE (ed) Handbook of physiology, vol IV. Williams & Wilkins Co., Bethesda, Maryland, pp 463–524Google Scholar
  72. Feldman JL, Mitchell GS, Nattie EE (2003) Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci 26:239–266. doi: 10.1146/annurev.neuro.26.041002.131103 PubMedPubMedCentralCrossRefGoogle Scholar
  73. Fiacco TA, McCarthy KD (2006) Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia 54(7):676–690. doi: 10.1002/glia.20396 PubMedCrossRefGoogle Scholar
  74. Fukuda Y, Honda Y (1975) pH sensitive cells at ventrolateral surface of the rat medulla oblongata. Nat New Biol 256:317–318CrossRefGoogle Scholar
  75. Fukuda Y, Honda Y, Schlaefke ME, Loeschcke HH (1978) Effect of H+ on the membrane potential of silent cells in the ventral and dorsal surface layer of the rat medulla in vitro. Pflügers Arch 376:229–235PubMedCrossRefGoogle Scholar
  76. Funk GD (2010) The ‘connexin’ between astrocytes, ATP and central respiratory chemoreception. J Physiol 588(Pt 22):4335–4337. doi: 10.1113/jphysiol.2010.200196 PubMedPubMedCentralCrossRefGoogle Scholar
  77. Funk GD, Johnson SM, Smith JC, Dong X-W, Lai J, Feldman JL (1997) Functional respiratory rhythm generating networks in neonatal mice lacking NMDAR1 gene. J Neurophysiol 78:1414–1420PubMedGoogle Scholar
  78. Furukawa S, Furukawa Y, Satoyoshi E, Hayashi K (1986) Synthesis and secretion of nerve growth factor by mouse astroglial cells in culture. Biochem Biophys Res Commun 136(1):57–63PubMedCrossRefGoogle Scholar
  79. Gahring LC, Persiyanov K, Rogers SW (2004) Neuronal and astrocyte expression of nicotinic receptor subunit beta4 in the adult mouse brain. J Comp Neurol 468(3):322–333. doi: 10.1002/cne.10942 PubMedCrossRefGoogle Scholar
  80. Gebicke-Haerter PJ, Seregi A, Schobert A, Hertting G (1988) Involvement of protein kinase C in prostaglandin D(2) synthesis by cultured astrocytes. Neurochem Int 13(4):475–480PubMedCrossRefGoogle Scholar
  81. Goridis C, Dubreuil V, Thoby-Brisson M, Fortin G, Brunet JF (2010) Phox2b, congenital central hypoventilation syndrome and the control of respiration. Sem Cell Dev Biol 21(8):814–822. doi: 10.1016/j.semcdb.2010.07.006 CrossRefGoogle Scholar
  82. Gotts J, Atkinson L, Edwards IJ, Yanagawa Y, Deuchars SA, Deuchars J (2015) Co-expression of GAD67 and choline acetyltransferase reveals a novel neuronal phenotype in the mouse medulla oblongata. Auton Neurosci. doi: 10.1016/j.autneu.2015.05.003 PubMedPubMedCentralGoogle Scholar
  83. Gourine AV, Kasparov S (2011) Astrocytes as brain interoceptors. Exp Physiol 96(4):411–416. doi: 10.1113/expphysiol.2010.053165 PubMedCrossRefGoogle Scholar
  84. Gourine AV, Llaudet E, Dale N, Spyer KM (2005) ATP is a mediator of chemosensory transduction in the central nervous system. Nature 436(7047):108–111. doi: 10.1038/nature03690 PubMedCrossRefGoogle Scholar
  85. Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010) Astrocytes control breathing through pH-dependent release of ATP. Science 329(5991):571–575. doi: 10.1126/science.1190721 PubMedPubMedCentralCrossRefGoogle Scholar
  86. Grass D, Pawlowski PG, Hirrlinger J, Papadopoulos N, Richter DW, Kirchhoff F, Hulsmann S (2004) Diversity of functional astroglial properties in the respiratory network. J Neurosci 24(6):1358–1365. doi: 10.1523/JNEUROSCI.4022-03.2004 PubMedCrossRefGoogle Scholar
  87. Gray PA, Hayes JA, Ling GY, Llona I, Tupal S, Picardo MC, Ross SE, Hirata T, Corbin JG, Eugenin J, Del Negro CA (2010) Developmental origin of preBotzinger complex respiratory neurons. J Neurosci 30(44):14883–14895. doi: 10.1523/JNEUROSCI.4031-10.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  88. Greer JJ, Smith JC, Feldman JL (1991) Role of excitatory amino acids in the generation and transmission of respiratory drive in neonatal rat. J Physiol 437:727–749PubMedPubMedCentralCrossRefGoogle Scholar
  89. Guček A, Vardjan N, Zorec R (2012) Exocytosis in astrocytes: transmitter release and membrane signal regulation. Neurochem Res 37(11):2351–2363. doi: 10.1007/s11064-012-0773-6 PubMedCrossRefGoogle Scholar
  90. Guthrie PB, Knappenberger J, Segal M, Bennett MV, Charles AC, Kater SB (1999) ATP released from astrocytes mediates glial calcium waves. J Neurosci 19(2):520–528PubMedGoogle Scholar
  91. Guyenet PG, Mulkey DK (2010) Retrotrapezoid nucleus and parafacial respiratory group. Respir Physiol Neurobiol 173(3):244–255. doi: 10.1016/j.resp.2010.02.005 PubMedPubMedCentralCrossRefGoogle Scholar
  92. Guyenet PG, Mulkey DK, Stornetta RL, Bayliss DA (2005) Regulation of ventral surface chemoreceptors by the central respiratory pattern generator. J Neurosci 25(39):8938–8947PubMedCrossRefGoogle Scholar
  93. Halassa MM, Haydon PG (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol 72:335–355. doi: 10.1146/annurev-physiol-021909-135843 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Hamilton NB, Attwell D (2010) Do astrocytes really exocytose neurotransmitters? Nat Rev 11(4):227–238. doi: 10.1038/nrn2803 CrossRefGoogle Scholar
  95. Hartel K, Schnell C, Hulsmann S (2009) Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal mice. Glia 57(8):815–827. doi: 10.1002/glia.20808 PubMedCrossRefGoogle Scholar
  96. Hartung HP, Toyka KV (1987) Phorbol diester TPA elicits prostaglandin E release from cultured rat astrocytes. Brain Res 417(2):347–349PubMedCrossRefGoogle Scholar
  97. Hartung HP, Heininger K, Schafer B, Toyka KV (1988) Substance P stimulates release of arachidonic acid cyclooxygenation products from primary culture rat astrocytes. Ann N Y Acad Sci 540:427–429PubMedCrossRefGoogle Scholar
  98. Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86(3):1009–1031. doi: 10.1152/physrev.00049.2005 PubMedCrossRefGoogle Scholar
  99. Henneberger C, Papouin T, Oliet SH, Rusakov DA (2010) Long-term potentiation depends on release of D-serine from astrocytes. Nature 463(7278):232–236. doi: 10.1038/nature08673 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Hibino H, Fujita A, Iwai K, Yamada M, Kurachi Y (2004) Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes. J Biol Chem 279(42):44065–44073. doi: 10.1074/jbc.M405985200 PubMedCrossRefGoogle Scholar
  101. Hirata Y, Oku Y (2010) TRP channels are involved in mediating hypercapnic Ca2+ responses in rat glia-rich medullary cultures independent of extracellular pH. Cell Calcium 48(2–3):124–132. doi: 10.1016/j.ceca.2010.07.006 PubMedCrossRefGoogle Scholar
  102. Hodges MR, Klum L, Leekley T, Brozoski DT, Bastasic J, Davis S, Wenninger JM, Feroah TR, Pan LG, Forster HV (2004a) Effects on breathing in awake and sleeping goats of focal acidosis in the medullary raphe. J Appl Physiol 96(5):1815–1824. doi: 10.1152/japplphysiol.00992.2003 (1985)PubMedCrossRefGoogle Scholar
  103. Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HV (2004b) Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats. J Appl Physiol 97(6):2236–2247PubMedCrossRefGoogle Scholar
  104. Hodges MR, Tattersall GJ, Harris MB, McEvoy SD, Richerson DN, Deneris ES, Johnson RL, Chen ZF, Richerson GB (2008) Defects in breathing and thermoregulation in mice with near-complete absence of central serotonin neurons. J Neurosci 28(10):2495–2505PubMedCrossRefGoogle Scholar
  105. Hodges MR, Best S, Richerson GB (2011) Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice. Respir Physiol Neurobiol 177(2):133–140. doi: 10.1016/j.resp.2011.03.020 PubMedPubMedCentralCrossRefGoogle Scholar
  106. Holleran J, Babbie M, Erlichman JS (2001) Ventilatory effects of impaired glial function in a brainstem chemoreceptor region in the conscious rat. J Appl Physiol 90:1539–1547PubMedGoogle Scholar
  107. Hosli E, Hosli L (1994a) Binding of cholecystokinin, bombesin and muscarine to neurons and astrocytes in explant cultures of rat central nervous system: autoradiographic and immunohistochemical studies. Neuroscience 61(1):63–72PubMedCrossRefGoogle Scholar
  108. Hosli E, Hosli L (1994b) Colocalization of binding sites for somatostatin, muscarine and nicotine on cultured neurones of rat neocortex, cerebellum, brain stem and spinal cord: combined autoradiographic and immunohistochemical studies. Neurosci Lett 173(1–2):71–74PubMedCrossRefGoogle Scholar
  109. Hosli L, Hosli E, Della-Briotta G, Quadri L, Heuss L (1988) Action of acetylcholine, muscarine, nicotine and antagonists on the membrane potential of astrocytes in cultured rat brainstem and spinal cord. Neurosci Lett 92(2):165–170PubMedCrossRefGoogle Scholar
  110. Hosli L, Hosli E, Winter T, Stauffer S (1994) Coexistence of cholinergic and somatostatin receptors on astrocytes of rat CNS. NeuroReport 5(12):1469–1472PubMedCrossRefGoogle Scholar
  111. Huckstepp RT, Eason R, Sachdev A, Dale N (2010a) CO2-dependent opening of connexin 26 and related beta connexins. J Physiol 588(Pt 20):3921–3931. doi: 10.1113/jphysiol.2010.192096 PubMedPubMedCentralCrossRefGoogle Scholar
  112. Huckstepp RT, id Bihi R, Eason R, Spyer KM, Dicke N, Willecke K, Marina N, Gourine AV, Dale N (2010b) Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J Physiol 588(Pt 20):3901–3920. doi: 10.1113/jphysiol.2010.192088 PubMedPubMedCentralCrossRefGoogle Scholar
  113. Huda R, McCrimmon DR, Martina M (2013) pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract. J Neurophysiol 110:368–377. doi: 10.1152/jn.01074.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  114. Hulsmann S (2000) Metabolic coupling between glia and neurons is necessary for maintaining respiratory activity in transverse medulary slices of neonatal mouse. Eur J Neurosci 12:7Google Scholar
  115. Hulsmann S, Straub H, Richter DW, Speckmann EJ (2003) Blockade of astrocyte metabolism causes delayed excitation as revealed by voltage-sensitive dyes in mouse brainstem slices. Exp Brain Res 150(1):117–121. doi: 10.1007/s00221-003-1410-z PubMedGoogle Scholar
  116. Huxtable AG, Zwicker JD, Alvares TS, Ruangkittisakul A, Fang X, Hahn LB, Posse de Chaves E, Baker GB, Ballanyi K, Funk GD (2010) Glia contribute to the purinergic modulation of inspiratory rhythm-generating networks. J Neurosci 30(11):3947–3958. doi: 10.1523/JNEUROSCI.6027-09.2010 PubMedCrossRefGoogle Scholar
  117. Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10(11):1369–1376. doi: 10.1038/nn2003 PubMedCrossRefGoogle Scholar
  118. Iceman KE, Richerson GB, Harris MB (2013) Medullary serotonin neurons are CO2 sensitive in situ. J Neurophysiol 110(11):2536–2544. doi: 10.1152/jn.00288.2013 PubMedPubMedCentralCrossRefGoogle Scholar
  119. Infante CD, von Bernhardi R, Rovegno M, Llona I, Eugenin JL (2003) Respiratory responses to pH in the absence of pontine and dorsal medullary areas in the newborn mouse in vitro. Brain Res 984(1–2):198–205PubMedCrossRefGoogle Scholar
  120. Kadle R, Suksang C, Roberson ED, Fellows RE (1988) Identification of an insulin-like factor in astrocyte conditioned medium. Brain Res 460(1):60–67PubMedCrossRefGoogle Scholar
  121. Kanbar R, Stornetta RL, Cash DR, Lewis SJ, Guyenet PG (2010) Photostimulation of Phox2b medullary neurons activates cardiorespiratory function in conscious rats. Am J Respir Crit Care Med 182(9):1184–1194. doi: 10.1164/rccm.201001-0047OC PubMedPubMedCentralCrossRefGoogle Scholar
  122. Kang BJ, Chang DA, Mackay DD, West GH, Moreira TS, Takakura AC, Gwilt JM, Guyenet PG, Stornetta RL (2007) Central nervous system distribution of the transcription factor Phox2b in the adult rat. J Comp Neurol 503(5):627–641. doi: 10.1002/cne.21409 PubMedCrossRefGoogle Scholar
  123. Kasymov V, Larina O, Castaldo C, Marina N, Patrushev M, Kasparov S, Gourine AV (2013) Differential sensitivity of brainstem versus cortical astrocytes to changes in pH reveals functional regional specialization of astroglia. J Neurosci 33(2):435–441. doi: 10.1523/JNEUROSCI.2813-12.2013 PubMedPubMedCentralCrossRefGoogle Scholar
  124. Kimelberg HK, Goderie SK, Higman S, Pang S, Waniewski RA (1990) Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures. J Neurosci 10(5):1583–1591PubMedGoogle Scholar
  125. Kinney HC, Filiano JJ, Sleeper LA, Mandell F, Valdes-Dapena M, White WF (1995) Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome. Science 269(5229):1446–1450PubMedCrossRefGoogle Scholar
  126. Krause KL, Forster HV, Davis SE, Kiner T, Bonis JM, Pan LG, Qian B (2009) Focal acidosis in the pre-Botzinger complex area of awake goats induces a mild tachypnea. J Appl Physiol 106(1):241–250. doi: 10.1152/japplphysiol.90547.2008 (1985)PubMedCrossRefGoogle Scholar
  127. Krzan M, Stenovec M, Kreft M, Pangrsic T, Grilc S, Haydon PG, Zorec R (2003) Calcium-dependent exocytosis of atrial natriuretic peptide from astrocytes. J Neurosci 23(5):1580–1583PubMedGoogle Scholar
  128. Kuwaki T, Li A, Nattie E (2010) State-dependent central chemoreception: a role of orexin. Respir Physiol Neurobiol 173(3):223–229. doi: 10.1016/j.resp.2010.02.006 PubMedPubMedCentralCrossRefGoogle Scholar
  129. Lee MG, Hassani OK, Jones BE (2005) Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J Neurosci 25(28):6716–6720. doi: 10.1523/JNEUROSCI.1887-05.2005 PubMedCrossRefGoogle Scholar
  130. Li A, Nattie EE (1995) Prolonged stimulation of respiration by brain stem metabotropic glutamate receptors. J Appl Physiol 79(5):1650–1656PubMedGoogle Scholar
  131. Li A, Nattie E (2002) CO2 dialysis in one chemoreceptor site, the RTN: stimulus intensity and sensitivity in the awake rat. Respir Physiol Neurobiol 133(1–2):11–22PubMedCrossRefGoogle Scholar
  132. Li A, Nattie E (2008) Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia. J Physiol 586(9):2321–2329. doi: 10.1113/jphysiol.2008.152231 PubMedPubMedCentralCrossRefGoogle Scholar
  133. Li A, Nattie E (2010) Antagonism of rat orexin receptors by almorexant attenuates central chemoreception in wakefulness in the active period of the diurnal cycle. J Physiol 588(Pt 15):2935–2944. doi: 10.1113/jphysiol.2010.191288 PubMedPubMedCentralCrossRefGoogle Scholar
  134. Li A, Randall M, Nattie EE (1999) CO(2) microdialysis in retrotrapezoid nucleus of the rat increases breathing in wakefulness but not in sleep. J Appl Physiol 87(3):910–919PubMedGoogle Scholar
  135. Li A, Zhou S, Nattie E (2006) Simultaneous inhibition of caudal medullary raphe and retrotrapezoid nucleus decreases breathing and the CO2 response in conscious rats. J Physiol 577(Pt 1):307–318PubMedPubMedCentralCrossRefGoogle Scholar
  136. Li N, Li A, Nattie E (2013) Focal microdialysis of CO(2) in the perifornical-hypothalamic area increases ventilation during wakefulness but not NREM sleep. Respir Physiol Neurobiol 185(2):349–355. doi: 10.1016/j.resp.2012.09.007 PubMedCrossRefGoogle Scholar
  137. Loeschcke HH (1982) Central chemosensitivity and the reaction theory. J Physiol 332:1–24PubMedPubMedCentralCrossRefGoogle Scholar
  138. Lorier AR, Huxtable AG, Robinson DM, Lipski J, Housley GD, Funk GD (2007) P2Y1 receptor modulation of the pre-Botzinger complex inspiratory rhythm generating network in vitro. J Neurosci 27(5):993–1005. doi: 10.1523/JNEUROSCI.3948-06.2007 PubMedCrossRefGoogle Scholar
  139. Makara JK, Petheö GL, Tóth A, Spät A (2001) pH-sensitive inwardly rectifying chloride current in cultured rat cortical astrocytes. Glia 34:52–58PubMedCrossRefGoogle Scholar
  140. Mallios VJ, Lydic R, Baghdoyan HA (1995) Muscarinic receptor subtypes are differentially distributed across brain stem respiratory nuclei. Am J Physiol 268:L941–L949PubMedGoogle Scholar
  141. Marina N, Abdala AP, Trapp S, Li A, Nattie EE, Hewinson J, Smith JC, Paton JF, Gourine AV (2010) Essential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration. J Neurosci 30(37):12466–12473. doi: 10.1523/JNEUROSCI.3141-10.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  142. Martino PF, Davis S, Opansky C, Krause K, Bonis JM, Pan LG, Qian B, Forster HV (2007) The cerebellar fastigial nucleus contributes to CO2-H+ ventilatory sensitivity in awake goats. Respir Physiol Neurobiol 157(2–3):242–251. doi: 10.1016/j.resp.2007.01.019 PubMedPubMedCentralCrossRefGoogle Scholar
  143. Meigh L, Greenhalgh SA, Rodgers TL, Cann MJ, Roper DI, Dale N (2013) CO(2)directly modulates connexin 26 by formation of carbamate bridges between subunits. Elife 2:e01213. doi: 10.7554/eLife.01213 PubMedPubMedCentralCrossRefGoogle Scholar
  144. Mercure L, Tannenbaum GS, Schipper HM, Phaneuf D, Wainberg MA (1996) Expression of the somatostatin gene in human astrocytoma cell lines. Clin Diagn Lab Immunol 3(2):151–155PubMedPubMedCentralGoogle Scholar
  145. Messier ML, Li A, Nattie EE (2002) Muscimol inhibition of medullary raphe neurons decreases the CO2 response and alters sleep in newborn piglets. Respir Physiol Neurobiol 133(3):197–214PubMedCrossRefGoogle Scholar
  146. Messier ML, Li A, Nattie EE (2004) Inhibition of medullary raphe serotonergic neurons has age-dependent effects on the CO2 response in newborn piglets. J Appl Physiol 96(5):1909–1919PubMedCrossRefGoogle Scholar
  147. Mitchell RA, Loeschcke HH, Massion WH, Severinghaus JW (1963) Respiratory responses mediated through superficial chemosensitive areas on the medulla. J Appl Physiol 18(3):523–533Google Scholar
  148. Monteau R, Morin D, Hilaire G (1990) Acetylcholine and central chemosensitivity: in vitro study in the newborn rat. Respir Physiol 81:241–254PubMedCrossRefGoogle Scholar
  149. Morgado-Valle C, Feldman JL (2007) NMDA receptors in preBotzinger complex neurons can drive respiratory rhythm independent of AMPA receptors. J Physiol 582(Pt 1):359–368. doi: 10.1113/jphysiol.2007.130617 PubMedPubMedCentralCrossRefGoogle Scholar
  150. Mulkey DK, Stornetta RL, Weston MC, Simmons JR, Parker A, Bayliss DA, Guyenet PG (2004) Respiratory control by ventral surface chemoreceptor neurons in rats. Nat Neurosci 7(12):1360–1369PubMedCrossRefGoogle Scholar
  151. Mulkey DK, Mistry AM, Guyenet PG, Bayliss DA (2006) Purinergic P2 receptors modulate excitability but do not mediate pH sensitivity of RTN respiratory chemoreceptors. J Neurosci 26(27):7230–7233. doi: 10.1523/JNEUROSCI.1696-06.2006 PubMedCrossRefGoogle Scholar
  152. Murphy S, Minor RL Jr, Welk G, Harrison DG (1990) Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide. J Neurochem 55(1):349–351PubMedCrossRefGoogle Scholar
  153. Nakamura A, Zhang W, Yanagisawa M, Fukuda Y, Kuwaki T (2007) Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice. J Appl Physiol 102(1):241–248. doi: 10.1152/japplphysiol.00679.2006 (1985)PubMedCrossRefGoogle Scholar
  154. Nattie E (1999) CO2, brainstem chemoreceptors and breathing. Prog Neurobiol 59(4):299–331PubMedCrossRefGoogle Scholar
  155. Nattie EE (2001) Central chemosensitivity, sleep, and wakefulness. Respir Physiol 129(1–2):257–268PubMedCrossRefGoogle Scholar
  156. Nattie E (2011) Julius H. Comroe, Jr., distinguished lecture: central chemoreception: then … and now. J Appl Physiol 110(1):1–8. doi: 10.1152/japplphysiol.01061.2010 PubMedCrossRefGoogle Scholar
  157. Nattie E, Li A (1990) Ventral medulla sites of muscarinic receptor subtypes involved in cardiorespiratory control. J Appl Physiol 69(1):33–41PubMedGoogle Scholar
  158. Nattie EE, Li A (1994) Retrotrapezoid nucleus lesions decrease phrenic activity and CO2 sensitivity in rats. Respir Physiol 97(1):63–77PubMedCrossRefGoogle Scholar
  159. Nattie EE, Li A (1995) Rat retrotrapezoid nucleus iono- and metabotropic glutamate receptors and the control of breathing. J Appl Physiol 78(1):153–163PubMedGoogle Scholar
  160. Nattie E, Li A (2000) Muscimol dialysis in the retrotrapezoid nucleus region inhibits breathing in the awake rat. J Appl Physiol 89(1):153–162PubMedGoogle Scholar
  161. Nattie EE, Li A (2001) CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep. J Appl Physiol 90(4):1247–1257PubMedGoogle Scholar
  162. Nattie EE, Li A (2002a) CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness. J Appl Physiol 92(5):2119–2130PubMedCrossRefGoogle Scholar
  163. Nattie EE, Li A (2002b) Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol 544(Pt 2):603–616PubMedPubMedCentralCrossRefGoogle Scholar
  164. Nattie E, Li A (2006) Central chemoreception 2005: a brief review. Auton Neurosci 126–127:332–338PubMedCrossRefGoogle Scholar
  165. Nattie G, Li A (2008) Multiple central chemoreceptor sites: cell types and function in vivo. Adv Exp Med Biol 605:343–347PubMedCrossRefGoogle Scholar
  166. Nattie E, Li A (2009) Central chemoreception is a complex system function that involves multiple brain stem sites. J Appl Physiol 106(4):1464–1466. doi: 10.1152/japplphysiol.00112.2008 PubMedCrossRefGoogle Scholar
  167. Nattie E, Li A (2010) Central chemoreception in wakefulness and sleep: evidence for a distributed network and a role for orexin. J Appl Physiol 108(5):1417–1424. doi: 10.1152/japplphysiol.01261.2009 PubMedPubMedCentralCrossRefGoogle Scholar
  168. Nattie E, Li A (2012) Central chemoreceptors: locations and functions. Compr Physiol 2(1):221–254. doi: 10.1002/cphy.c100083 PubMedPubMedCentralGoogle Scholar
  169. Nattie EE, Wood J, Mega A, Goritski W (1989) Rostral ventrolateral medulla muscarinic receptor involvement in central ventilatory chemosensitivity. J Appl Physiol 66(3):1462–1470PubMedGoogle Scholar
  170. Nattie EE, Fung ML, Li A, St John WM (1993a) Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus to CO2. Respir Physiol 94(1):35–50PubMedCrossRefGoogle Scholar
  171. Nattie EE, Gdovin M, Li A (1993b) Retrotrapezoid nucleus glutamate receptors: control of CO2-sensitive phrenic and sympathetic output. J Appl Physiol 74(6):2958–2968PubMedGoogle Scholar
  172. Nattie EE, Li A, Mills J, Huang Q (1994) Retrotrapezoid nucleus muscarinic receptor subtypes localized by autoradiography. Respir Physiol 96(2–3):189–197PubMedCrossRefGoogle Scholar
  173. Nattie EE, Li A, Richerson GB, Lappi DA (2004) Medullary serotonergic neurones and adjacent neurones that express neurokinin-1 receptors are both involved in chemoreception in vivo. J Physiol 556(Pt 1):235–253. doi: 10.1113/jphysiol.2003.059766 PubMedPubMedCentralCrossRefGoogle Scholar
  174. Neusch C, Papadopoulos N, Muller M, Maletzki I, Winter SM, Hirrlinger J, Handschuh M, Bahr M, Richter DW, Kirchhoff F, Hulsmann S (2006) Lack of the Kir4.1 channel subunit abolishes K+ buffering properties of astrocytes in the ventral respiratory group: impact on extracellular K+ regulation. J Neurophysiol 95(3):1843–1852. doi: 10.1152/jn.00996.2005 PubMedCrossRefGoogle Scholar
  175. Newton K, Malik V, Lee-Chiong T (2014) Sleep and breathing. Clin Chest Med 35(3):451–456. doi: 10.1016/j.ccm.2014.06.001 PubMedCrossRefGoogle Scholar
  176. Nichols NL, Wilkinson KA, Powell FL, Dean JB, Putnam RW (2009) Chronic hypoxia suppresses the CO2 response of solitary complex (SC) neurons from rats. Respir Physiol Neurobiol 168(3):272–280. doi: 10.1016/j.resp.2009.07.012 PubMedPubMedCentralCrossRefGoogle Scholar
  177. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067PubMedCrossRefGoogle Scholar
  178. Oberheim NA, Takano T, Han X, He W, Lin JH, Wang F, Xu Q, Wyatt JD, Pilcher W, Ojemann JG, Ransom BR, Goldman SA, Nedergaard M (2009) Uniquely hominid features of adult human astrocytes. J Neurosci 29(10):3276–3287. doi: 10.1523/JNEUROSCI.4707-08.2009 PubMedPubMedCentralCrossRefGoogle Scholar
  179. Oberheim NA, Goldman SA, Nedergaard M (2012) Heterogeneity of astrocytic form and function. Methods Mol Biol 814:23–45. doi: 10.1007/978-1-61779-452-0_3 PubMedPubMedCentralCrossRefGoogle Scholar
  180. Ohno K, Sakurai T (2008) Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol 29(1):70–87. doi: 10.1016/j.yfrne.2007.08.001 PubMedCrossRefGoogle Scholar
  181. Onimaru H, Homma I (2006) Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Botzinger complex (preBotC) is the primary site of respiratory rhythm generation in the mammal. Point: the PFRG is the primary site of respiratory rhythm generation in the mammal. J Appl Physiol 100(6):2094–2095PubMedCrossRefGoogle Scholar
  182. Onimaru H, Kumagawa Y, Homma I (2006) Respiration-related rhythmic activity in the rostral medulla of newborn rats. J Neurophysiol 96(1):55–61PubMedCrossRefGoogle Scholar
  183. Onimaru H, Ikeda K, Kawakami K (2008) CO2-sensitive preinspiratory neurons of the parafacial respiratory group express Phox2b in the neonatal rat. J Neurosci 28(48):12845–12850. doi: 10.1523/JNEUROSCI.3625-08.2008 PubMedCrossRefGoogle Scholar
  184. Onimaru H, Ikeda K, Kawakami K (2009) Phox2b, RTN/pFRG neurons and respiratory rhythmogenesis. Respir Physiol Neurobiol 168(1–2):13–18. doi: 10.1016/j.resp.2009.03.007 PubMedCrossRefGoogle Scholar
  185. Oyamada Y, Ballantyne D, Muckenhoff K, Scheid P (1998) Respiration-modulated membrane potential and chemosensitivity of locus coeruleus neurones in the in vitro brainstem-spinal cord of the neonatal rat. J Physiol (London) 513(Pt 2):381–398CrossRefGoogle Scholar
  186. Paixao S, Klein R (2010) Neuron-astrocyte communication and synaptic plasticity. Curr Opin Neurobiol 20(4):466–473. doi: 10.1016/j.conb.2010.04.008 PubMedCrossRefGoogle Scholar
  187. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369(6483):744–747. doi: 10.1038/369744a0 PubMedCrossRefGoogle Scholar
  188. Paterson DS, Thompson EG, Kinney HC (2006) Serotonergic and glutamatergic neurons at the ventral medullary surface of the human infant: Observations relevant to central chemosensitivity in early human life. Auton Neurosci 124(1–2):112–124. doi: 10.1016/j.autneu.2005.12.009 PubMedCrossRefGoogle Scholar
  189. Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF (1999) The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399(6734):366–370. doi: 10.1038/20700 PubMedCrossRefGoogle Scholar
  190. Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91(22):10625–10629PubMedPubMedCentralCrossRefGoogle Scholar
  191. Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55(12):1251–1262. doi: 10.1002/glia.20528 PubMedCrossRefGoogle Scholar
  192. Perea G, Araque A (2010) GLIA modulates synaptic transmission. Brain Res Rev 63(1–2):93–102. doi: 10.1016/j.brainresrev.2009.10.005 PubMedCrossRefGoogle Scholar
  193. Perea G, Sur M, Araque A (2014) Neuron-glia networks: integral gear of brain function. Front Cell Neurosci 8:378. doi: 10.3389/fncel.2014.00378 PubMedPubMedCentralCrossRefGoogle Scholar
  194. Ramanantsoa N, Hirsch MR, Thoby-Brisson M, Dubreuil V, Bouvier J, Ruffault PL, Matrot B, Fortin G, Brunet JF, Gallego J, Goridis C (2011) Breathing without CO2 chemosensitivity in conditional Phox2b mutants. J Neurosci 31(36):12880–12888. doi: 10.1523/JNEUROSCI.1721-11.2011 PubMedCrossRefGoogle Scholar
  195. Ray RS, Corcoran AE, Brust RD, Kim JC, Richerson GB, Nattie E, Dymecki SM (2011) Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition. Science 333(6042):637–642. doi: 10.1126/science.1205295 PubMedPubMedCentralCrossRefGoogle Scholar
  196. Ray RS, Corcoran AE, Brust RD, Soriano LP, Nattie EE, Dymecki SM (2013) Egr2-neurons control the adult respiratory response to hypercapnia. Brain Res 1511:115–125. doi: 10.1016/j.brainres.2012.12.017 PubMedCrossRefGoogle Scholar
  197. Richerson GB (1995) Response to CO2 of neurons in the rostral ventral medulla in vitro. J Neurophysiol 73(3):933–944PubMedGoogle Scholar
  198. Richter DW, Spyer KM (2001) Studying rhythmogenesis of breathing: comparison of in vivo and in vitro models. Trends Neurosci 24(8):464–472PubMedCrossRefGoogle Scholar
  199. Richter DW, Camerer H, Sonnhof U (1978) Changes in extracellular potassium during the spontaneous activity of medullary respiratory neurones. Pflugers Arch 376(2):139–149PubMedCrossRefGoogle Scholar
  200. Ritucci NA, Erlichman JS, Leiter JC, Putnam RW (2005) Response of membrane potential and intracellular pH to hypercapnia in neurons and astrocytes from rat retrotrapezoid nucleus. Am J Physiol 289:R851–R861. doi: 10.1152/ajpregu.00132.2005.-We CrossRefGoogle Scholar
  201. Rodriguez-Arellano JJ, Parpura V, Zorec R, Verkhratsky A (2015) Astrocytes in physiological aging and Alzheimer’s disease. Neuroscience. doi: 10.1016/j.neuroscience.2015.01.007 PubMedGoogle Scholar
  202. Rosenberg D, Kartvelishvily E, Shleper M, Klinker CM, Bowser MT, Wolosker H (2010) Neuronal release of D-serine: a physiological pathway controlling extracellular D-serine concentration. FASEB J 24(8):2951–2961. doi: 10.1096/fj.09-147967 PubMedPubMedCentralCrossRefGoogle Scholar
  203. Ruggiero DA, Giuliano R, Anwar M, Stornetta R, Reis DJ (1990) Anatomical substrates of cholinergic-autonomic regulation in the rat. J Comp Neurol 292(1):1–53. doi: 10.1002/cne.902920102 PubMedCrossRefGoogle Scholar
  204. Sakurai T (2014) The role of orexin in motivated behaviours. Nat Rev 15(11):719–731. doi: 10.1038/nrn3837 CrossRefGoogle Scholar
  205. Schell MJ, Molliver ME, Snyder SH (1995) D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release. Proc Natl Acad Sci USA 92(9):3948–3952PubMedPubMedCentralCrossRefGoogle Scholar
  206. Schmitt BM, Berger UV, Douglas RM, Bevensee MO, Hediger MA, Haddad GG, Boron WF (2000) Na/HCO3 cotransporters in rat brain: expression in glia, neurons, and choroid plexus. J Neurosci 20(18):6839–6848PubMedGoogle Scholar
  207. Schnell C, Fresemann J, Hulsmann S (2011) Determinants of functional coupling between astrocytes and respiratory neurons in the pre-Botzinger complex. PLoS One 6(10):e26309. doi: 10.1371/journal.pone.0026309 PubMedPubMedCentralCrossRefGoogle Scholar
  208. Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF (1990) Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol 144(1):129–135PubMedGoogle Scholar
  209. Shao XM, Feldman JL (2005) Cholinergic neurotransmission in the preBotzinger Complex modulates excitability of inspiratory neurons and regulates respiratory rhythm. Neuroscience 130(4):1069–1081PubMedPubMedCentralCrossRefGoogle Scholar
  210. Shao XM, Feldman JL (2009) Central cholinergic regulation of respiration: nicotinic receptors. Acta Pharmacol Sin 30(6):761–770. doi: 10.1038/aps.2009.88 PubMedPubMedCentralCrossRefGoogle Scholar
  211. Shao XM, Tan W, Xiu J, Puskar N, Fonck C, Lester HA, Feldman JL (2008) Alpha4* nicotinic receptors in preBotzinger complex mediate cholinergic/nicotinic modulation of respiratory rhythm. J Neurosci 28(2):519–528. doi: 10.1523/JNEUROSCI.3666-07.2008 PubMedPubMedCentralCrossRefGoogle Scholar
  212. Shinoda H, Marini AM, Cosi C, Schwartz JP (1989) Brain region and gene specificity of neuropeptide gene expression in cultured astrocytes. Science 245(4916):415–417PubMedCrossRefGoogle Scholar
  213. Sidoryk-Wegrzynowicz M, Wegrzynowicz M, Lee E, Bowman AB, Aschner M (2011) Role of astrocytes in brain function and disease. Toxicol Pathol 39(1):115–123. doi: 10.1177/0192623310385254 PubMedCrossRefGoogle Scholar
  214. Smith JC, Ellenberger H, Ballanyi K, Richter DW, Feldman JL (1991) Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254(5032):726–729PubMedPubMedCentralCrossRefGoogle Scholar
  215. Sobrinho CR, Wenker IC, Poss EM, Takakura AC, Moreira TS, Mulkey DK (2014) Purinergic signalling contributes to chemoreception in the retrotrapezoid nucleus but not the nucleus of the solitary tract or medullary raphe. J Physiol 592(Pt 6):1309–1323. doi: 10.1113/jphysiol.2013.268490 PubMedPubMedCentralCrossRefGoogle Scholar
  216. Solomon IC (2003) Focal CO2/H+ alters phrenic motor output response to chemical stimulation of cat pre-Botzinger complex in vivo. J Appl Physiol 94(6):2151–2157PubMedCrossRefGoogle Scholar
  217. Solomon IC, Edelman NH, O’Neal MH 3rd (2000) CO(2)/H(+) chemoreception in the cat pre-Botzinger complex in vivo. J Appl Physiol 88(6):1996–2007PubMedGoogle Scholar
  218. Spyer KM, Dale N, Gourine AV (2004) ATP is a key mediator of central and peripheral chemosensory transduction. Exp Physiol 89(1):53–59PubMedCrossRefGoogle Scholar
  219. Stipursky J, Romao L, Tortelli V, Neto VM, Gomes FC (2011) Neuron-glia signaling: Implications for astrocyte differentiation and synapse formation. Life Sci 89(15–16):524–531. doi: 10.1016/j.lfs.2011.04.005 PubMedCrossRefGoogle Scholar
  220. Stornetta RL, Moreira TS, Takakura AC, Kang BJ, Chang DA, West GH, Brunet JF, Mulkey DK, Bayliss DA, Guyenet PG (2006) Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat. J Neurosci 26(40):10305–10314. doi: 10.1523/JNEUROSCI.2917-06.2006 PubMedCrossRefGoogle Scholar
  221. Stornetta RL, Macon CJ, Nguyen TM, Coates MB, Guyenet PG (2013) Cholinergic neurons in the mouse rostral ventrolateral medulla target sensory afferent areas. Brain Struct Funct 218(2):455–475. doi: 10.1007/s00429-012-0408-3 PubMedCrossRefGoogle Scholar
  222. Sunanaga J, Deng BS, Zhang W, Kanmura Y, Kuwaki T (2009) CO2 activates orexin-containing neurons in mice. Respir Physiol Neurobiol 166(3):184–186. doi: 10.1016/j.resp.2009.03.006 PubMedCrossRefGoogle Scholar
  223. Swanson RA, Graham SH (1994) Fluorocitrate and fluoroacetate effects on astrocyte metabolism in vitro. Brain Res 664(1–2):94–100PubMedCrossRefGoogle Scholar
  224. Szoke K, Hartel K, Grass D, Hirrlinger PG, Hirrlinger J, Hulsmann S (2006) Glycine transporter 1 expression in the ventral respiratory group is restricted to protoplasmic astrocytes. Brain Res 1119(1):182–189. doi: 10.1016/j.brainres.2006.08.089 PubMedCrossRefGoogle Scholar
  225. Takakura AC, Moreira TS, Stornetta RL, West GH, Gwilt JM, Guyenet PG (2008) Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apnoeic threshold in rats. J Physiol 586(Pt 12):2975–2991. doi: 10.1113/jphysiol.2008.153163 jphysiol.2008.153163[pii]PubMedPubMedCentralCrossRefGoogle Scholar
  226. Takakura AC, Barna BF, Cruz JC, Colombari E, Moreira TS (2014) Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571–585. doi: 10.1113/expphysiol.2013.076752 PubMedCrossRefGoogle Scholar
  227. Tatehata T, Shiosaka S, Wanaka A, Rao ZR, Tohyama M (1987) Immunocytochemical localization of the choline acetyltransferase containing neuron system in the rat lower brain stem. J Hirnforsch 28(6):707–716PubMedGoogle Scholar
  228. Taylor NC, Li A, Nattie EE (2006) Ventilatory effects of muscimol microdialysis into the rostral medullary raphe region of conscious rats. Respir Physiol Neurobiol 153(3):203–216PubMedCrossRefGoogle Scholar
  229. Teppema LJ, Veening JG, Kranenburg A, Dahan A, Berkenbosch A, Olievier C (1997) Expression of c-fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia. J Comp Neurol 388(2):169–190PubMedCrossRefGoogle Scholar
  230. Terada J, Nakamura A, Zhang W, Yanagisawa M, Kuriyama T, Fukuda Y, Kuwaki T (2008) Ventilatory long-term facilitation in mice can be observed during both sleep and wake periods and depends on orexin. J Appl Physiol 104(2):499–507. doi: 10.1152/japplphysiol.00919.2007 (1985)PubMedCrossRefGoogle Scholar
  231. Thomas T, Spyer KM (2000) ATP as a mediator of mammalian central CO2 chemoreception. J Physiol (London) 523(Pt 2):441–447CrossRefGoogle Scholar
  232. Toyama S, Sakurai T, Tatsumi K, Kuwaki T (2009) Attenuated phrenic long-term facilitation in orexin neuron-ablated mice. Respir Physiol Neurobiol 168(3):295–302. doi: 10.1016/j.resp.2009.07.025 PubMedCrossRefGoogle Scholar
  233. Turovsky E, Karagiannis A, Abdala AP, Gourine AV (2015) Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome. J Physiol 593(14):3159–3168. doi: 10.1113/JP270369 PubMedPubMedCentralCrossRefGoogle Scholar
  234. von Euler C (1986) Brain stem mechanisms for generation and control of breathing pattern. In: Cherniack NS, Widdicombe JG (eds) American physiological society: handbook of physiology, vol 2., control of breathingWilliams & Wilkins Co., Baltimore, Maryland, pp 1–68Google Scholar
  235. Wang W, Richerson GB (1999) Development of chemosensitivity of rat medullary raphe neurons. Neuroscience 90(3):1001–1011PubMedCrossRefGoogle Scholar
  236. Wang W, Pizzonia JH, Richerson GB (1998) Chemosensitivity of rat medullary raphe neurones in primary tissue culture. J Physiol (London) 511(Pt 2):433–450CrossRefGoogle Scholar
  237. Wang S, Shi Y, Shu S, Guyenet PG, Bayliss DA (2013) Phox2b-expressing retrotrapezoid neurons are intrinsically responsive to H+ and CO2. J Neurosci 33(18):7756–7761. doi: 10.1523/JNEUROSCI.5550-12.2013 PubMedPubMedCentralCrossRefGoogle Scholar
  238. Wenker IC, Kreneisz O, Nishiyama A, Mulkey DK (2010) Astrocytes in the retrotrapezoid nucleus sense H+ by inhibition of a Kir4.1–Kir5.1-like current and may contribute to chemoreception by a purinergic mechanism. J Neurophysiol 104(6):3042–3052. doi: 10.1152/jn.00544.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  239. Wenker IC, Sobrinho CR, Takakura AC, Moreira TS, Mulkey DK (2012) Regulation of ventral surface CO2/H+ -sensitive neurons by purinergic signalling. J Physiol 590(Pt 9):2137–2150. doi: 10.1113/jphysiol.2012.229666 PubMedPubMedCentralCrossRefGoogle Scholar
  240. Westergaard N, Sonnewald U, Schousboe A (1994) Release of alpha-ketoglutarate, malate and succinate from cultured astrocytes: possible role in amino acid neurotransmitter homeostasis. Neurosci Lett 176(1):105–109PubMedCrossRefGoogle Scholar
  241. Wickstrom R, Hokfelt T, Lagercrantz H (2002) Development of CO(2)-response in the early newborn period in rat. Respir Physiol Neurobiol 132(2):145–158PubMedCrossRefGoogle Scholar
  242. Williams RH, Jensen LT, Verkhratsky A, Fugger L, Burdakov D (2007) Control of hypothalamic orexin neurons by acid and CO2. Proc Natl Acad Sci USA 104(25):10685–10690. doi: 10.1073/pnas.0702676104 PubMedPubMedCentralCrossRefGoogle Scholar
  243. Wolosker H (2011) Serine racemase and the serine shuttle between neurons and astrocytes. Biochim Biophys Acta. doi: 10.1016/j.bbapap.2011.01.001 PubMedGoogle Scholar
  244. Wu J, Xu H, Shen W, Jiang C (2004) Expression and coexpression of CO2-sensitive Kir channels in brainstem neurons of rats. J Membrane Biol 197:179–191. doi: 10.1007/s00232-004-0652-4 CrossRefGoogle Scholar
  245. Wu Z, Zhang J, Nakanishi H (2005) Leptomeningeal cells activate microglia and astrocytes to induce IL-10 production by releasing pro-inflammatory cytokines during systemic inflammation. J Neuroimmunol 167(1–2):90–98. doi: 10.1016/j.jneuroim.2005.06.025 PubMedCrossRefGoogle Scholar
  246. Xu F, Frazier DT (1995) Medullary respiratory neuronal activity modulated by stimulation of the fastigial nucleus of the cerebellum. Brain Res 705(1–2):53–64PubMedCrossRefGoogle Scholar
  247. Xu F, Zhang Z, Frazier DT (2001) Microinjection of acetazolamide into the fastigial nucleus augments respiratory output in the rat. J Appl Physiol 91(5):2342–2350PubMedGoogle Scholar
  248. Xu G, Wang W, Kimelberg HK, Zhou M (2010) Electrical coupling of astrocytes in rat hippocampal slices under physiological and simulated ischemic conditions. Glia 58(4):481–493. doi: 10.1002/glia.20939 PubMedGoogle Scholar
  249. Yao ST, Barden JA, Finkelstein DI, Bennett MR, Lawrence AJ (2000) Comparative study on the distribution patterns of P2X1-P2X6 receptor immunoreactivity in the brainstem of the rat and the common marmoset (Callithrix jacchus): association with catecholamine cell groups. J Comp Neurol 427:485–507PubMedCrossRefGoogle Scholar
  250. Young JK, Dreshaj IA, Wilson CG, Martin RJ, Zaidi SI, Haxhiu MA (2005a) An astrocyte toxin influences the pattern of breathing and the ventilatory response to hypercapnia in neonatal rats. Respir Physiol Neurobiol 147(1):19–30. doi: 10.1016/j.resp.2005.01.009 PubMedCrossRefGoogle Scholar
  251. Young JK, Wu M, Manaye KF, Kc P, Allard JS, Mack SO, Haxhiu MA (2005b) Orexin stimulates breathing via medullary and spinal pathways. J Appl Physiol 98(4):1387–1395. doi: 10.1152/japplphysiol.00914.2004 (1985)PubMedCrossRefGoogle Scholar
  252. Yudkoff M, Daikhin Y, Nissim I, Pleasure D, Stern J (1994) Inhibition of astrocyte glutamine production by alpha-ketoisocaproic acid. J Neurochem 63(4):1508–1515PubMedCrossRefGoogle Scholar
  253. Zwicker JD, Rajani V, Hahn LB, Funk GD (2011) Purinergic modulation of preBotzinger complex inspiratory rhythm in rodents: the interaction between ATP and adenosine. J Physiol 589(Pt 18):4583–4600. doi: 10.1113/jphysiol.2011.210930 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Jaime Eugenín León
    • 1
    Email author
  • María José Olivares
    • 1
  • Sebastián Beltrán-Castillo
    • 1
  1. 1.Departamento de BiologíaUniversidad de Santiago de Chile (USACH)SantiagoChile

Personalised recommendations