Journal of Neurology

, Volume 252, Supplement 4, pp iv5–iv12 | Cite as

The pedunculopontine tegmental nucleus and experimental parkinsonism

A review
  • Masaru MatsumuraEmail author


In this article, I review a series of my experiments on the role of the pedunculopontine tegmental nucleus (Ppn) in voluntary movements. I sought to elucidate the functional role of the Ppn in the control of voluntary movements using macaque monkeys. I propose a functional model of basal ganglia circuitry in which I emphasize the role of the Ppn and discuss the underlying mechanisms of parkinsonism.

Key words

Parkinson’s disease pedunculopontine tegmental nucleus monkey voluntary movement 


  1. 1.
    Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. TINS 12:366–375PubMedGoogle Scholar
  2. 2.
    Alexander GE (1994) Basal ganglia—thalamocortical circuits: Their role in control of movements. J Clin Neurophysiol 11:420–431PubMedGoogle Scholar
  3. 3.
    Aziz TZ, Davies L, Stein J, France S (1998) The role of descending basal ganglia connections to the brain stem in parkinsonian akinesia. Br J Neurosurg 12:245–249CrossRefPubMedGoogle Scholar
  4. 4.
    Carter CJ (1982) Topographic distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats. Neuropharmacology 21:379–383CrossRefPubMedGoogle Scholar
  5. 5.
    Charara A, Smith Y, Parent A (1996) Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates; Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistry. J Comp Neurol 364:254–266CrossRefPubMedGoogle Scholar
  6. 6.
    Condé H, Dormont JF, Farin D (1998) The role of pedunculopontine tegmental nucleus in relation to conditioned motor performance in the cat. II. Effects of reversible inactivation by intracerebral microinjections. Exp Brain Res 121:411–418CrossRefPubMedGoogle Scholar
  7. 7.
    Crossman AR (1987) Primate models of dyskinesia—The experimental approach to the study of basal ganglia-related involuntary movement disorders. Neuroscience 21:1–40CrossRefPubMedGoogle Scholar
  8. 8.
    Davis GC, Williams AC, Markey SP, Evert MH, Caine ED, Reichert CM, Kopin IJ (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychat Res 1:249–254CrossRefGoogle Scholar
  9. 9.
    DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285CrossRefPubMedGoogle Scholar
  10. 10.
    Dormont JF, Condé H, Farin D (1998) The role of pedunculopontine tegmental nucleus in relation to conditioned motor performance in the cat. I. Context-dependent and reinforcement-related single unit activity. Exp Brain Res 121:401–410CrossRefPubMedGoogle Scholar
  11. 11.
    Filion M (1979) Effects of interruption of the nigrostriatal pathway and of the dopaminergic agents on the spontaneous activity of globus pallidus neurons in the awake monkey. Brain Res 178:425–441CrossRefPubMedGoogle Scholar
  12. 12.
    Filion M, Tremblay L (1991) Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547:142–151CrossRefPubMedGoogle Scholar
  13. 13.
    Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272PubMedGoogle Scholar
  14. 14.
    Futami T, Takakusaki K, Kitai ST (1995) Glutamatergic and cholinergic inputs from the pedunculopontine tegmental nucleus to dopamine neurons in the substantia nigra pars compacta. Neurosci Res 21:331–342CrossRefPubMedGoogle Scholar
  15. 15.
    Garcia-Rill E (1986) The basal ganglia and the locomotor regions. Brain Res Rev 11:47–63CrossRefGoogle Scholar
  16. 16.
    Garicia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36:363–389CrossRefPubMedGoogle Scholar
  17. 17.
    Garcia-Rill E, Skinner RD (1988) Modulation of rhythmic function in the superior midbrain. Neuroscience 27:639–654CrossRefPubMedGoogle Scholar
  18. 18.
    Hallanger AE, Levey AI, Lee HJ, Rye DB, Wainer BH (1987) The origins of cholinergic and other subcortical afferents to the thalamus in the rat. J Comp Neurol 262:105–124CrossRefPubMedGoogle Scholar
  19. 19.
    Harnois C, Filion M (1980) Pallidal neurons branching to the thalamus and to the midbrain in the monkey. Brain Res 186:222–225CrossRefPubMedGoogle Scholar
  20. 20.
    Harnois C, Filion M (1982) Pallidofugal projections to the thalamus and to the midbrain: A quantitative antidromic activation study in monkeys and cats. Exp Brain Res 47:277–285CrossRefPubMedGoogle Scholar
  21. 21.
    Hartmann-von Monakow K, Akert K, Künzle H (1979) Projections of precentral and premotor cortex to the red nucleus and other midbrain areas in Macaca fascicularis. Exp Brain Res 34:91–105PubMedGoogle Scholar
  22. 22.
    Hazratti L-N, Parent A (1991) Contralateral pallidothalamic and pallidotegmental projections in primates: an anterograde and retrograde labeling study. Brain Res 567:212–223CrossRefPubMedGoogle Scholar
  23. 23.
    Hazratti L-N, Parent A (1992) Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the squirrel monkey. Brain Res 585:267–271CrossRefPubMedGoogle Scholar
  24. 24.
    Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84:5976–5980PubMedGoogle Scholar
  25. 25.
    Inglis WL, Winn P (1995) The pedunculopontine tegmental nucleus: where the striatum meets the reticular formation. Prog Neurobiol 47:1–29CrossRefPubMedGoogle Scholar
  26. 26.
    Jackson A, Crossman AR (1983) Nucleus tegmenti pedunculopontinus: efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase. Neuroscience 10:725–765CrossRefPubMedGoogle Scholar
  27. 27.
    Jellinger K (1988) The pedunculopontine nucleus in Parkinson’s disease, progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 51:540–543PubMedGoogle Scholar
  28. 28.
    Kang Y, Kitai ST (1990) Electrophysiological properties of pedunculopontine neurons and their postsynaptic responses following stimulation of substantia nigra pars reticulata. Brain Res 535:79–95CrossRefPubMedGoogle Scholar
  29. 29.
    Kita H, Kitai ST (1987) Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method. J Comp Neurol 260:435–452CrossRefPubMedGoogle Scholar
  30. 30.
    Kobayashi Y, Inoue Y,Yamamoto M, Isa T, Aizawa H (2002) Contribution of pedunculopontine tegmental nucleus neurons to performance of visually guided saccade tasks in monkeys. J Neurophysiol 88:715–731Google Scholar
  31. 31.
    Kobayashi Y, Saito Y, Isa T (2001) Facilitation of saccade initiation by brainstem cholinergic system. Brain and Development 23:S24–S27CrossRefPubMedGoogle Scholar
  32. 32.
    Kojima J, Yamaji Y, Matsumura M, Nambu A, Inase M, Tokuno H, Takada M, Imai H (1997) Excitotoxic lesions of the pedunculopontine tegmental nucleus produce contralateral hemiparkinsonism in the monkey. Neurosci Lett 226:111–114CrossRefPubMedGoogle Scholar
  33. 33.
    Langston JW, Ballard PA, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–980PubMedGoogle Scholar
  34. 34.
    Lavoie B, Parent A (1994) Pedunculopontine nucleus in the squirrel monkey: Distribution of cholinergic and monoaminergic neurons in the mesopontine tegmentum with evidence for the presence of glutamate in cholinergic neurons. J Comp Neurol 344:190–209CrossRefPubMedGoogle Scholar
  35. 35.
    Lavoie B, Parent A (1994) Pedunculopontine nucleus in the squirrel monkey: projections to the basal ganglia as revealed by anterograde tract-tracing methods. J Comp Neurol 344:210–231CrossRefPubMedGoogle Scholar
  36. 36.
    Lavoie B, Parent A (1994) Pedunculopontine nucleus in the squirrel monkey: cholinergic and glutamatergic projections to the substantia nigra. J Comp Neurol 344:232–241CrossRefPubMedGoogle Scholar
  37. 37.
    Lozano AM, Lang AE (1998) Pallidotomy for Parkinson’s disease-review. Neurosurg Clin N Am 9:325–336PubMedGoogle Scholar
  38. 38.
    Matsumura M (2001) Experimental parkinsonism in primates. Stereotactic Funct Neurosurg 77:91–97CrossRefGoogle Scholar
  39. 39.
    Matsumura M, Nambu A, Yamaji Y, Watanabe K, Imai H, Inase M, Tokuno H, Takada M (2000) Organization of somatic motor inputs from the frontal lobe to the pedunculopontine tegemental nucleus in the macaque monkey. Neuroscience 98:97–110CrossRefPubMedGoogle Scholar
  40. 40.
    Matsumura M, Tremblay L, Richard H, Filion M (1995) Activity of pallidal neurons in the monkey during dyskinesia induced by injection of bicuculline in the external pallidum. Neuroscience 65:59–70CrossRefPubMedGoogle Scholar
  41. 41.
    Matsumura M, Watanabe K, Ohye C (1996) Neuronal activity of monkey pedunculopontine tegmental nucleus area. I. Activity related to voluntary arm movements. In: Ohye C, Kimura M, McKenzie J (eds) The Basal Ganglia V, Plenum Press, New York, pp 209–215Google Scholar
  42. 42.
    Matsumura M, Watanabe K, Ohye C (1997) Single-unit activity in the primate nucleus tegmenti pedunculopintinus related to voluntary arm movement. Neurosci Res 28:155–165CrossRefPubMedGoogle Scholar
  43. 43.
    Matsumura M, Watanabe K, Ohye C (2002) Effects of reversible blockade of pedunculopontine tegmental nucleus on a voluntary arm movement in monkeys. In Graybiel AM, DeLong MR (eds) The Basal Ganglia VI, Kluwer Academic/Plenum Publishers, New York, pp 151–158Google Scholar
  44. 44.
    Mena-Segovia J, Bolam PJ, Magill PJ (2004) Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family? TINS 27:585–588PubMedGoogle Scholar
  45. 45.
    Mesulam MM, Geula C, Bothwell MA, Hersh LB (1989) Human reticular formation. Cholinergic neurons of the pedunculopontine and laterodosal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons. J Comp Neurol 283:611–623CrossRefPubMedGoogle Scholar
  46. 46.
    Mitchell IJ, Clarke CE, Boyce S, Robertson RG, Peggs D, Sambrook MA (1989) Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-metyl-4-phynyl-1,2,3,6-tetrahydropyridine. Neuroscience 32:213–226CrossRefPubMedGoogle Scholar
  47. 47.
    Moon Edley S, Graybiel AM (1983) The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus pars compacta. J Comp Neurol 217:187–215CrossRefPubMedGoogle Scholar
  48. 48.
    Munro-Davies LE, Winter J, Aziz TZ, Stein JF (1999) The role of the pedunculopontine region in basal-ganglia mechanisms of akinesia. Exp Brain Res 129:511–517CrossRefPubMedGoogle Scholar
  49. 49.
    Nakano K, Hasegawa Y, Tokushige A, Nakagawa S, Kayahara T, Mizuno N (1990) Topographical projections from the thalamus, subthalamic nucleus and pedunculopontine tegmental nucleus to the striatum in the Japanese monkey, Macaca fuscata. Brain Res 537:54–68CrossRefPubMedGoogle Scholar
  50. 50.
    Nandi D, Aziz TZ, Giladi N, Winter J, Stein JF (2002) Reversal of akinesia in experimental parkinsonism by GABA antagonist microinjections in the pedunculopontine nucleus. Brain 125:2418–2430CrossRefPubMedGoogle Scholar
  51. 51.
    Olszewski J, Baxter D (1982) Cytoarchitecture of the Human Brain Stem. 2nd ed,Karger, Basale, p 195Google Scholar
  52. 52.
    Pahapill PA, Lozano AM (2000) The pedunculopontine nucleus and Parkinson’s disease. Brain 123:1747–1783CrossRefGoogle Scholar
  53. 53.
    Paré D, Smith Y, Parent A, Steriade M (1988) Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei. Neuroscience 25:69–86CrossRefPubMedGoogle Scholar
  54. 54.
    Parent A, Côté P-Y, Lavoie B (1995) Chemical anatomy of primate basal ganglia. Prog Neurobiol 46:131–197CrossRefPubMedGoogle Scholar
  55. 55.
    Parent A, Hazrati L-N (1995) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamocortical loop. Brain Res Rev 20:91–127CrossRefPubMedGoogle Scholar
  56. 56.
    Parent M, Lévesque M, Parent A (1999) The pallidofugal projection system in primates: evidence for neurons branching ipsilaterally and contralaterally to the thalamus and brainstem. Review. J Chemical Neuroanatomy 16:153–165CrossRefGoogle Scholar
  57. 57.
    Parent A, Mackey A, De Bellefeuille L (1983) The subcortical afferents to caudate nucleus and putamen in primate: A fluorescence retrograde double labeling study. Neuroscience 10:1137–1150CrossRefPubMedGoogle Scholar
  58. 58.
    Poirier LJ (1960) Experimental and histological study of midbrain dyskinesia. J Neurophysiol 23:534–551PubMedGoogle Scholar
  59. 59.
    Reese NB, Garcial-Rill E, Skinner RD (1995) The pedunculopontine nucleusauditory input, arousal and pathophysiology. Progr Neurobiol 42:105–133CrossRefGoogle Scholar
  60. 60.
    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 269:315–341CrossRefPubMedGoogle Scholar
  61. 61.
    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 259:483–528CrossRefPubMedGoogle Scholar
  62. 62.
    Saitoh K, Hattori S, Song W-J, Isa T, Takakusaki K (2003) Nigral GABAergic inhibition upon cholinergic neurons in the rat pedunculopontine tegmental nucleus. Eur J Neurosci 18:879–886CrossRefPubMedGoogle Scholar
  63. 63.
    Sakai ST (1988) Corticonigral projections from area 6 in the raccoon. Exp Brain Res 73:498–504CrossRefPubMedGoogle Scholar
  64. 64.
    Scarnati E, Proia A, Di Loreto S, Pacitti C (1987) The reciprocal electrophysiological influence between the nucleus tegmenti pedunculopontinus and the pars compacta of the substantia nigra in the rat. J Hirnforsh 1:95–105Google Scholar
  65. 65.
    Scarnati E, Florio T (1997) The pedunculopontine nucleus and related structures. Functional organization. Adv Neurol 74:97–110PubMedGoogle Scholar
  66. 66.
    Shink E, Sidibé M, Smith Y (1997) Efferent connections of the internal globus pallidus in the squirrel monkey: II. Topography and synaptic organization of pallidal efferents to the pedunculopontine nucleus. J Comp Neurol 382:348–363CrossRefPubMedGoogle Scholar
  67. 67.
    Skinner RD, Kinjo N, Henderson V, Garcia-Rill E (1990) Locomotor projections from the pedunculopontine nucleus to the spinal cord. NeuroRep 1:183–186Google Scholar
  68. 68.
    Smith Y, Charara A, Paquet M, Kieval JZ, Paré J-F, Hanson JE, Hubert GW, Kuwajima M, Levey AI (2001) Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia. J Chemical Neuroanatomy 22:13–42CrossRefGoogle Scholar
  69. 69.
    Smith Y, Charara A, Parent A (1996) Synaptic innervation of midbrain dopaminergic neurons by glutamate-enriched terminals in the squirrel monkey. J Comp Neurol 364:231–253CrossRefPubMedGoogle Scholar
  70. 70.
    Spann BM,Grofova I (1989) Origin of ascending and spinal pathways from the nucleus tegmenti pedunculopontinus in the rat. J Comp Neurol 283:13–27CrossRefPubMedGoogle Scholar
  71. 71.
    Spann BM, Grofova I (1991) Nigropedunculopontine projection in the rat: An anterograde tracing study with Phaseolus vulgaris leudoaggulutinin (PHA-L). J Comp Neurol 311:375–388CrossRefPubMedGoogle Scholar
  72. 72.
    Steckler T, Inglis W, Winn P, Sahgal A (1994) The pedunculopontine tegmental nucleus: a role in cognitive process? Brain Res Rev 19:298–318CrossRefPubMedGoogle Scholar
  73. 73.
    Steriade M, Paré D, Parent A, Smith Y (1988) Projections of cholinergic and non-cholinergic neurons of the brainstem core to relay and associational thalamic nuclei in the cat and macaque monkey. Neuroscience 25:47–67CrossRefPubMedGoogle Scholar
  74. 74.
    Takada M, Matsumura M, Kojima J, Yamaji Y, Inase M, Tokuno H, Nambu A, Imai H (2000) Protection against dopaminergic nigrostriatal cell death by excitatory input ablation. Eur J Neurosci 12:1771–1780CrossRefPubMedGoogle Scholar
  75. 75.
    Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J, Saitoh K, Sakamoto T (2003) Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: A new concept for understanding motor disorders in basal ganglia dysfunction. Neuroscience 119:293–308CrossRefPubMedGoogle Scholar
  76. 76.
    Takakusaki K, Saitoh K, Harada H, Kashiwayanagi M (2004) Role of basal ganglia-brainstem pathways in the control of motor behaviors. Neurosci Res 50:137–151CrossRefPubMedGoogle Scholar
  77. 77.
    Takakusaki K, Shiroyama T, Yamamoto T, Kitai ST (1996) Cholinergic and noncholinergic tegmental pedunculopontine projection neurons in rats revealed by intracellular labeling. J Comp Neurol 371:345–361CrossRefPubMedGoogle Scholar
  78. 78.
    Tokuno H, Moriizumi T, Kudo M, Nakamura Y (1988) A morphological evidence for monosynaptic projections from the nucleus tegmenti pedunculopontinus pars compacta (TPC) to nigrostriatal projection neurons. Neurosci Lett 85:1–4CrossRefPubMedGoogle Scholar
  79. 79.
    Watanabe K, Matsumura M, Ohye C (1996) Neuronal activity of monkey pedunculopontine tegmental nucleus area. II. Activity related to load application on working arms. In: Ohye C, Kimura M, McKenzie J (eds) The Basal Ganglia V, Plenum Press, New York, pp 249–257Google Scholar
  80. 80.
    Wichmann T, DeLong MR (1996) Functional and pathophysiological models of the basal ganglia. Curr Opin Neurobiol 6:751–758CrossRefPubMedGoogle Scholar
  81. 81.
    Winn P (1998) Frontal syndrome as a consequence of lesions in the pedunculopontine tegmental nucleus: A short theoretical review. Brain Res Bull 47:551–563CrossRefPubMedGoogle Scholar
  82. 82.
    Winn P, Brown VJ, Inglis WL (1997) On the relationship between the striatum and the pedunculopontine tegmental nucleus. Crit Rev Neurobiol 11:241–261PubMedGoogle Scholar
  83. 83.
    Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL (1989) The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol 26:41–46CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  1. 1.Neuroscience and NeurosurgeryChuo Gunma Neurosurgery HospitalGunma, 370-0001Japan

Personalised recommendations