Sleep and Breathing

, Volume 10, Issue 4, pp 195–202

Modulation of respiratory pattern and upper airway muscle activity by the pedunculopontine tegmentum: role of NMDA receptors

  • Jasna Saponjic
  • Miodrag Radulovacki
  • David W. Carley
Original Article

Abstract

The pedunculopontine tegmental nucleus (PPT) is postulated to have important functions relevant to the regulation of rapid eye movement (REM) sleep and arousal, and various motor control systems including respiration. We have recently shown that pharmacologic activation of a neuronal subpopulation within the PPT, induced by micropipette injection of glutamate in nanoliter volumes, can produce respiratory rhythm disturbances and changes in genioglossus muscle activity in anesthetized rats. The aim of this study was to determine whether the respiratory pattern disturbance and increased genioglossus muscle tone induced by glutamate injection within the PPT are mediated by activation of N-methyl-D-aspartate (NMDA) receptors within the PPT. Experiments were performed in eight adult male spontaneously breathing Sprague-Dawley rats anesthetized using nembutal. Respiratory movements were monitored by piezoelectric strain gauge. Three-barrel glass pipettes were used to pressure inject glutamate (as a probe for respiratory modulating sites), ketamine (an NMDA channel blocker), and oil-red dye (to aid in histological verification of the injection sites) within the PPT. Electroencephalograms were recorded from the sensorimotor cortex, the hippocampus, and the pons, contralateral to the injection site. Electromyograms (EMGs) were recorded from the genioglossus muscle. The typical response to glutamate injection within the PPT respiratory-modulating region was immediate apnea followed by tachypnea and increased genioglossal tonic activity. The noncompetitive NMDA receptor channel-antagonist ketamine, injected at the same site and in the same volume as glutamate (5 nl), blocked respiratory dysrhythmia and genioglossal EMG responses to subsequent glutamate injections. For the first time, the present results suggest that respiratory rhythm and upper airway muscle tone are controlled by the activation of pedunculopontine tegmental nucleus NMDA receptors.

Keywords

Pedunculopontine tegmental nucleus Respiratory dysrhythmia Genioglossus muscle activity Glutamate Ketamine Rapid eye movement sleep 

References

  1. 1.
    Vertes RP (1984) Brainstem control of the events of REM sleep. Prog Neurobiol 22(3):241–288PubMedCrossRefGoogle Scholar
  2. 2.
    Bringmann A (1995) Different functions of rat’s pedunculopontine tegmental nucleus are reflected in cortical EEG. Neuroreport 6(15):2065–2068PubMedCrossRefGoogle Scholar
  3. 3.
    Bringmann A (1997) Nicotine affects the occipital theta rhythm after lesion of the pedunculopontine tegmental nucleus in rats. Neuropsychobiology 35(2):102–107PubMedCrossRefGoogle Scholar
  4. 4.
    Kleiner S, Bringmann A (1996) Nucleus basalis magnocellularis and pedunculopontine tegmental nucleus: control of the slow EEG waves in rats. Arch Ital Biol 134(2):153–167PubMedGoogle Scholar
  5. 5.
    Rye DB (1997) Contributions of the pedunculopontine region to normal and altered REM sleep. Sleep 20(9):757–788PubMedGoogle Scholar
  6. 6.
    Datta S, Siwek DF (1997) Excitation of the brain stem pedunculopontine tegmentum cholinergic cells induces wakefulness and REM sleep. J Neurophysiol 77(6):2975–2988PubMedGoogle Scholar
  7. 7.
    Datta S, Spoley EE, Patterson EH (2001) Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat. Am J Physiol Regul Integr Comp Physiol 280(3):R752–R759PubMedGoogle Scholar
  8. 8.
    Datta S (2002) Evidence that REM sleep is controlled by the activation of brain stem pedunculopontine tegmental kainate receptor. J Neurophysiol 87(4):1790–1798PubMedGoogle Scholar
  9. 9.
    Inglis WL, Allen LF, Whitelaw RB, Latimer MP, Brace HM, Winn P (1994) An investigation into the role of the pedunculopontine tegmental nucleus in the mediation of locomotion and orofacial stereotypy induced by D-amphetamine and apomorphine in the rat. Neuroscience 58(4):817–833PubMedCrossRefGoogle Scholar
  10. 10.
    Takakusaki K, Habaguchi T, Saitoh K, Kohyama J (2004) Changes in the excitability of hindlimb motoneurons during muscular atonia induced by stimulating the pedunculopontine tegmental nucleus in cats. Neuroscience 124(2):467–480PubMedCrossRefGoogle Scholar
  11. 11.
    Saper CB, Loewy AD (1982) Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry. Brain Res 252(2):367–372PubMedCrossRefGoogle Scholar
  12. 12.
    Lydic R, Baghdoyan HA (1993) Pedunculopontine stimulation alters respiration and increases ACh release in the pontine reticular formation. Am J Physiol 264(3 Pt 2):R544–R554PubMedGoogle Scholar
  13. 13.
    Radulovacki M, Pavlovic S, Saponjic J, Carley DW (2004) Modulation of reflex and sleep related apnea by pedunculopontine tegmental and intertrigeminal neurons. Respir Physiol Neurobiol 143(2–3):293–306PubMedCrossRefGoogle Scholar
  14. 14.
    Saponjic J, Radulovacki M, Carley DW (2003) Respiratory pattern modulation by the pedunculopontine tegmental nucleus. Respir Physiol Neurobiol 138(2–3):223–237PubMedCrossRefGoogle Scholar
  15. 15.
    Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council (1996) Guide for the Care and Use of Laboratory Animals. National Academy of Sciences, Washington, DCGoogle Scholar
  16. 16.
    Datta S (1995) Neuronal activity in the peribrachial area: relationship to behavioral state control. Neurosci Biobehav Rev 19:67–84PubMedCrossRefGoogle Scholar
  17. 17.
    Datta S (1997) Cellular basis of pontine ponto-geniculo-occipital wave generation and modulation. Cell Mol Neurobiol 17(3):341–365PubMedCrossRefGoogle Scholar
  18. 18.
    Garcia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36(5):363–389PubMedCrossRefGoogle Scholar
  19. 19.
    Woolf NJ, Butcher LL (1986) Cholinergic systems in the rat brain: III. Projections from the pontomesen cephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain. Brain Res Bull 16(5):603–637PubMedCrossRefGoogle Scholar
  20. 20.
    Woolf NJ, Butcher LL (1989) Cholinergic systems in the rat brain: IV. Descending projections of the pontomesen cephalic tegmentum. Brain Res Bull 23(6):519–540PubMedCrossRefGoogle Scholar
  21. 21.
    Rye DB, Saper CB, Lee HJ, Wainer BH (1987) Pedunculopontine tegmental nucleus of the rat: cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum. J Comp Neurol 259(4):483–528PubMedCrossRefGoogle Scholar
  22. 22.
    Rye DB, Lee HJ, Saper CB, Wainer BH (1988) Medullary and spinal efferents of the pedunculopontine tegmental nucleus and adjacent mesopontine tegmentum in the rat. J Comp Neurol 269(3):315–341PubMedCrossRefGoogle Scholar
  23. 23.
    Semba K, Fibiger HC (1992) Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: a retro- and antero-grade transport and immunohistochemical study. J Comp Neurol 323(3):387–410PubMedCrossRefGoogle Scholar
  24. 24.
    Semba K (1993) Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat. J Comp Neurol 330(4):543–556PubMedCrossRefGoogle Scholar
  25. 25.
    Maloney KJ, Cape EG, Gotman J, Jones BE (1997) High-frequency gamma electroencephalogram activity in association with sleep-wake states and spontaneous behaviors in the rat. Neuroscience 76(2):541–555PubMedCrossRefGoogle Scholar
  26. 26.
    Vertes RP, Colom LV, Fortin WJ, Bland BH (1993) Brainstem sites for the carbachol elicitation of the hippocampal theta rhythm in the rat. Exp Brain Res 96(3):419–429PubMedCrossRefGoogle Scholar
  27. 27.
    Nowacka A, Jurkowlaniec E, Trojniar W (2002) Microinjection of procaine into the pedunculopontine tegmental nucleus suppresses hippocampal theta rhythm in urethane-anesthetized rats. Brain Res Bull 58(4):377–384PubMedCrossRefGoogle Scholar
  28. 28.
    Datta S, Calvo JM, Quattrochi J, Hobson JA (1992) Cholinergic microstimulation of the peribrachial nucleus in the cat. I. Immediate and prolonged increases in ponto-geniculo-occipital waves. Arch Ital Biol 130(4):263–284PubMedGoogle Scholar
  29. 29.
    Sanford LD, Tejani-Butt SM, Ross RJ, Morrison AR (1996) Elicited PGO waves in rats: lack of 5-HT1A inhibition in putative pontine generator region. Pharmacol Biochem Behav 53(2):323–327PubMedCrossRefGoogle Scholar
  30. 30.
    Saponjic J, Radulovacki M, Carley DW (2003) P-Waves are coupled to long-lasting respiratory disturbance following glutamate stimulation of the pedunculo-pontine tegmental nucleus (PPT). Sleep 26:A45–A46Google Scholar
  31. 31.
    Kubin L, Tojima H, Reignier C, Pack AI, Davies RO (1996) Interaction of serotonergic excitatory drive to hypoglossal motoneurons with carbachol-induced, REM sleep-like atonia. Sleep 19(3):187–195PubMedGoogle Scholar
  32. 32.
    Pack AI (1988) Changes in respiratory motor activity during rapid eye movement sleep. Chest 94:1200–1204Google Scholar
  33. 33.
    Hendricks JC, Kline LR, Kovalski RJ, O’Brien JA, Morrison AR, Pack AI (1991) Phasic respiratory muscle patterns and sleep-disordered breathing during rapid eye movement sleep in the English bulldog. Am Rev Respir Dis 144:1112–1120PubMedGoogle Scholar
  34. 34.
    Millman RP, Knight H, Kline LR, Shore ET, Chung DC, Pack AI (1988) Changes in compartmental ventilation in association with eye movements during REM sleep. J Appl Physiol 65(3):1196–1202PubMedGoogle Scholar
  35. 35.
    Saponjic J, Radulovacki M, Carley DW (2005) Injection of glutamate into the pedunculopontine tegmental nuclei of anesthetized rat causes respiratory dysrhythmia and alters EEG and EMG power. Sleep Breath 9:82–91PubMedCrossRefGoogle Scholar
  36. 36.
    Saponjic J, Cvorovic J, Radulovacki M, Carley DW (2005) Serotonin and noradrenaline modulate respiratory pattern disturbances evoked by glutamate injection into the pedunculopontine tegmentum of anesthetized rats. Sleep 28(5):560–570PubMedGoogle Scholar
  37. 37.
    Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, San DiegoGoogle Scholar
  38. 38.
    Boucher Y, Pollin B, Azerad J (1993) Microinfusions of excitatory amino acid antagonists into the trigeminal sensory complex antagonize the jaw opening reflex in freely moving rats. Brain Res 614(1–2):155–163PubMedCrossRefGoogle Scholar
  39. 39.
    Yasui Y, Cechetto DF, Saper CB (1990) Evidence for a cholinergic projection from the pedunculopontine tegmental nucleus to the rostral ventrolateral medulla in the rat. Brain Res 517(1–2):19–24PubMedCrossRefGoogle Scholar
  40. 40.
    Hobson JA, McCarley RW, Wyzinski PW (1975) Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189(4196):55–58PubMedCrossRefGoogle Scholar
  41. 41.
    Liu RH, Fung SJ, Reddy VK, Barnes CD (1995) Localization of glutamatergic neurons in the dorsolateral pontine tegmentum projecting to the spinal cord of the cat with a proposed role of glutamate on lumbar motoneuron activity. Neuroscience 64(1):193–208PubMedCrossRefGoogle Scholar
  42. 42.
    Lai YY, Clements JR, Siegel JM (1993) Glutamatergic and cholinergic projections to the pontine inhibitory area identified with horseradish peroxidase retrograde transport and immunohistochemistry. J Comp Neurol 336(3):321–330PubMedCrossRefGoogle Scholar
  43. 43.
    Watanabe M, Mishina M, Inoue Y (1994) Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem. J Comp Neurol 343(4):520–531PubMedCrossRefGoogle Scholar
  44. 44.
    Petralia RS, Wang YX, Wenthold RJ (1994) Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. J Comp Neurol 349(1):85–110PubMedCrossRefGoogle Scholar
  45. 45.
    Sato K, Kiyama H, Tohyama M (1993) The differential expression patterns of messenger RNAs encoding non-N-methyl-D-aspartate glutamate receptor subunits (GluR1–4) in the rat brain. Neuroscience 52(3):515–539PubMedCrossRefGoogle Scholar
  46. 46.
    Ohishi H, Shigemoto R, Nakanishi S, Mizuno N (1993) Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat. Neuroscience 53(4):1009–1018PubMedCrossRefGoogle Scholar
  47. 47.
    Datta S, Patterson EH, Spoley EE (2001) Excitation of the pedunculopontine tegmental NMDA receptors induces wakefulness and cortical activation in the rat. J Neurosci Res 66(1):109–116PubMedCrossRefGoogle Scholar
  48. 48.
    Garcia-Rill E, Kinjo N, Atsuta Y, Ishikawa Y, Webber M, Skinner RD (1990) Posterior midbrain-induced locomotion. Brain Res Bull 24(3):499–508PubMedCrossRefGoogle Scholar
  49. 49.
    Somogyi J, Llewellyn-Smith IJ (2001) Patterns of colocalization of GABA, glutamate and glycine immunoreactivities in terminals that synapse on dendrites of noradrenergic neurons in rat locus coeruleus. Eur J Neurosci 14(2):219–228PubMedCrossRefGoogle Scholar
  50. 50.
    Szabo G, Kartarova Z, Hoertnagl B, Somogyi R, Sperk G (2000) Differential regulation of adult and embryonic glutamate decarboxylases in rat dentate granule cells after kainate-induced limbic seizures. Neuroscience 100(2):287–295PubMedCrossRefGoogle Scholar
  51. 51.
    Vesselkin NP, Rio JP, Adanina VO, Kenigfest NB, Reperant J (1995) Colocalization of glutamate and glycine in giant fiber synapses of the lamprey spinal cord. J Brain Res 36(2):229–237Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Jasna Saponjic
    • 1
    • 4
  • Miodrag Radulovacki
    • 2
  • David W. Carley
    • 1
    • 2
    • 3
  1. 1.Department of MedicineUniversity of IllinoisChicagoUSA
  2. 2.Department of PharmacologyUniversity of IllinoisChicagoUSA
  3. 3.Department of Medical-Surgical NursingUniversity of IllinoisChicagoUSA
  4. 4.Section of Pulmonary, Critical Care and Sleep MedicineDepartment of Medicine (MC 719)ChicagoUSA

Personalised recommendations