Glutamate-Like Immunoreactivity is Present within Cholinergic Neurons of the Laterodorsal Tegmental and Pedunculopontine Nuclei

  • J. R. Clements
  • D. D. Toth
  • D. A. Highfield
  • S. J. Grant
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 295)


For the last decade the functional organization pf cholinergic neurons has dominated studies of the basal forebrain. Cholinergic neurons in the brain, exclusive of motor neurons and interneurons, are found in two spatially separate groups (Armstrong et al., 1983, Mesulam et al., 1984). The rostral group, located in the basal forebrain, has received substantial attention because of its corticopedal projections (Mesulam et al., 1984) and its’ degeneration in Alzheimer’s disease (Coyle et al., 1983). The caudal group is found in the laterodorsal tegmental nucleus (LDT) and pedunculopontine nucleus (PPT) within the pontine tegmentum (Vincent et al., 1983; Mesulam et al., 1984; Satoh and Fibiger, 1986), and is the source of cholinergic innervation to the basal forebrain, thalamus and brainstem (Sofroniew et al., 1985; Hallenger et al., 1987; Maley et al., 1988; Rye et al., 1988; Jones, 1990).


Cholinergic Neuron Basal Forebrain Tegmental Nucleus Pedunculopontine Nucleus Pontine Tegmentum 
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  1. Armstrong, D.A., Saper, C.B., Levey, A.I., Wainer, B.H., and Terry, R.D., 1983, Distribution of cholinergic neurons in the rat brain demonstrated by the immuohistochemical localization of choline-acetyltransferase, J.Comp. Neurol., 200:53.CrossRefGoogle Scholar
  2. Beninato, M., and Spencer, R.F., 1987, Cholinergic projection to the rat substantia nigra from the pedunculopontine tegmental nucleus. Brain Res., 412:169.PubMedCrossRefGoogle Scholar
  3. Beninato, M., and Spencer, R.F., 1988, The cholinergic innervation of the rat substantia nigra: a light and electron microscopic immunohistochemical study, Exp. Brain Res., 72:178.PubMedCrossRefGoogle Scholar
  4. Brashear, H.R., Zaborszky, L., and Heimer, L., 1986, Distribution of gabaergic and cholinergic neurons in the rat diagonal band, Neurosci., 17:439.CrossRefGoogle Scholar
  5. Clarke, P.B.S., Hommer, D.W., Pert, A., and Skirboll, L.R., 1987, Innervation of substantia nigra neurons by cholinergic afferents from pedunculopontine nucleus in the rat: neuroanatomical and electrophysiological evidence, Neurosci., 23:1011.CrossRefGoogle Scholar
  6. Clements, J.R., and Grant, S.J., 1990a, Glutamate-like immunoreactivity in neurons of the laterodorsal tegmental and pedunculopontine nuclei, Neurosci. Lett., 120:70.PubMedCrossRefGoogle Scholar
  7. Clements, J.R., and Grant, S.J., 1990b, Glutamate and acetylcholine are colocalized in the laterodorsal tegmental and pedunculopontine nuclei., Neurosci. Abst., 16:1189.Google Scholar
  8. Clements, J.R., Magnussen, K.R., and Beitz, A.J., 1990, Ultrastructural description of glutamate-, aspartate-, taurine- and glycine- like immunoreactive terminals from five rat brain regions, J.Electron Microscopic Tech., 15:49.CrossRefGoogle Scholar
  9. Clements, J.R., Magnussen, K.R., Mullett, M.A., and Beitz, A.J., 1987, An ultrastructural description of glutamate- and taurine-like immunoreactive elements in the rat hippocampus, Neurosci. Suppl., 22:S123.Google Scholar
  10. Clements, J.R., Monaghan, P.L., Madl, J.E., Larson, A.A., and Beitz, A.J., 1986, An ultrastructural examination of glutamate- and aspartate-like immunoreactive cells and processes in the cerebellar cortex of the rat, Soc. Neurosci. Abstr., 12:462.Google Scholar
  11. Cooper, J.R., Bloom, F.E., and Roth, R.H., 1986, “The Biochemical Basis of Neuropharmacology, 5th ed.”, Oxford Univ. Press, NY.Google Scholar
  12. Coyle, J.T., Price, D.L., and DeLong, M.R., 1983, Alzheimer’s disease: A disorder of cortical cholinergic innervation, Science, 219:1184.PubMedCrossRefGoogle Scholar
  13. Crawley, J.N., Olschowka, J.A., Diz, D.I., and Jacobowitz, D.M., 1985, Behavioral investigation of the coexistence of substance P, corticotropin releasing factor, and acetylcholinesterase in lateral dorsal tegmental neurons projecting to the medial frontal cortex of the rat. Peptides, 6:891.PubMedCrossRefGoogle Scholar
  14. Docherty, M., Bradford, H.F., and Wu, Y.-Y., 1987, Co-release of glutamate and aspartate from cholinergic and GABAergic synaptosomes. Nature, 330:64.PubMedCrossRefGoogle Scholar
  15. Fisher, R.S., Buchwald, N.A., Hull, C.D., and Levine, M.S., 1987 GABAergic basal forebrain neurons project to.the neocortex: The localization of glutamic acid decarboxylase and choline acetyltransferase in feline corticipetal neurons, J.Comp. Neurol., 272:489.CrossRefGoogle Scholar
  16. Forloni, G., Grzanna, R., Blakely, R.D., and Coyle, J.T., 1987, Co-localization of N-acetyl-aspartyl-glutamate in central cholinergic, noradrenergic, and serotonergic neurons. Synapse, 1:455.PubMedCrossRefGoogle Scholar
  17. Fruend, T., and Antal, M., 1988, GABA containing neurons in the septum control inhibitory interneurons in the hippocampus. Nature, 336:170.CrossRefGoogle Scholar
  18. Garcia-Rill, E., Houser, C.R., Skinner, R.D., Smith, W., and Woodward, D.J., 1987, Locomotion inducing sites in the vicinity of the pedunculopontine nucleus. Brain Res. Bull., 18:731.PubMedCrossRefGoogle Scholar
  19. Goldsmith, M., and Kooy, D.V.D., 1988, Separate non-cholinergic descending projections and cholinergic ascending projections from the nucleus tegmenti pedunculopontinus, Brain Res., 445:386.PubMedCrossRefGoogle Scholar
  20. Gould, E., Woolf, N.J., and Butcher, L.L., 1989, Cholinergic projections to the substantia nigra from the pedunculopontine and lateral dorsal tegmental nuclei. Ngyrosci, 28:611.CrossRefGoogle Scholar
  21. Hallenger, A.E., Levey, A.I., Lee, H.J., Rye, D.B., and Wainer, B.H., 1987, The origins of cholinergic and other subcortical afferents to the thalamus in the rat, J.Comp. Neurol., 262:105.CrossRefGoogle Scholar
  22. Hertz, L., Kvamme, E., McGeer, E.G., and Schousboe, A., eds.,1983, “Glutamine, Glutamate and GABA in the Central Nervous System,” Alan R. Liss, New York.Google Scholar
  23. Hu, B., Steriade, M., and Deschenes, M., 1989, The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus, Neurosci., 31:13.CrossRefGoogle Scholar
  24. Jones, B.E., 1990, Immunohistochemical study of choline acetyltransferase-immunoreactive processes and cells innervating the pontomedullary reticular formation in the rat, J.Comp. Neurol., 295:485.PubMedCrossRefGoogle Scholar
  25. Kayama, Y., Sumitomo, I., and Ogawa, T., 1986, Does the ascending cholinergic projection inhibit or excite neurons in the rat thalamic reticular nucleus? J. Neurophys., 56:1310.Google Scholar
  26. Kiosaka, T., Tauchi, M., and Dahl, J.L., 1988, Cholinergic neurons containing GABA-like and/or glutamic acid decarboxylase-like immunoreactivities in various brain regions of the rat, Exp. Brain Res., 70:605.Google Scholar
  27. Lee, H.J., Rye, D.B., Hallenger, A.E., Levey, A.I., and Wainer, B.H., 1988, Cholinergic vs. noncholinergic efferents from the mesopontine tegmentum to the extrapyramidal motor system nuclei., J. Comp. Neurol., 275:469.PubMedCrossRefGoogle Scholar
  28. Leonard, C.S., and Llinas, R., 1988, Electrophysiology of thalamic-projecting cholinergic brainstem neurons and their inhibition by ACh, Neurosci. Abstr., 14:297.Google Scholar
  29. Lewis, P.R. and C.C.D. Shute., 1967. The cholinergic limbic system: Projection to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest. Brain., 90: 521.PubMedCrossRefGoogle Scholar
  30. Maley, B.E., Frick, M.L., Levey, A.I., Wainer, B.H., and Eide, R.P., 1988, Immunohistochemistry of choline acetyltransferase in the guinea pig brain, Neurosci. Lett., 84:137.PubMedCrossRefGoogle Scholar
  31. Matsuzaki, T., Shiosaka, S., Inagaki, S., Sakanaka, M., Takatsuki, K., Takagi, H., Senba, E., Kawai, Y., and Tohyama, M., 1981, Distribution of neuropeptides in the dorsal pontine tegmental area of the rat. Cell. Molec.ßiolw., 27:499.Google Scholar
  32. McDonald, A.J., Beitz, A.J., Larson, A.A., Kuriyama, R., Sellitto, C., and Madl, J.E., 1989, Co-localization of glutamate and tubulin in putative excitatory neurons of the hippocampus and amygdala: an immunohistochemical study using monoclonal antibodies, Neuroscience, 30:405.PubMedCrossRefGoogle Scholar
  33. Mesulam, M.-M., Mufson, E.J., Levey, A.I., and Wainer, B.H., 1984, Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry, Neurosci., 12:669.CrossRefGoogle Scholar
  34. Miller, K.E., Clements, J.R., Larson, A.A., and Beitz, A.J., 1988, Organization of glutamate-like immunoreactivity in the rat superficial dorsal horn: light and electron microscopic observations. Synapse., 2:28.PubMedCrossRefGoogle Scholar
  35. Mogenson, G.J., and Yang, C.R., 1991, The contribution of basal forebrain to limbic motor integration and the mediation of motivation to action, in: “The Basal Forebrain: Anatomy to Function”, T.C. Napier, P.W. Kalivas, and I. Hanin, eds., Plenum Press, New York, (in press).Google Scholar
  36. Ottersen, O.P., and Storm-Mathiesen, J., 1984, Glutamate- and GABA- containing neurons in the mouse and rat brain, as demonstrated with a new immunocytochemical technique, J.Comp. Neurol., 229:374.PubMedCrossRefGoogle Scholar
  37. Petrusz, P., and Rustioni, A., 1989, Immunocytochemistry of excitatory amino acids in brain, in: “Techniques in Immunocytochemistry, Vol 4.”, G.R. Bullock and P. Petrusz, ed., Academic Press, New York, p. 253.Google Scholar
  38. Richardson, R.T., and DeLong, M.R., 1991, Electrophysiological studies of the functions of the nucleus basalis in primates, in: “The Basal Forebrain: Anatomy to Function”, T.C. Napier, P.W. Kalivas, and I. Hanin, eds., Plenum Press, New York, (in press).Google Scholar
  39. Rye, D.B., Lee, H.J., Saper, C.B., and Wainer, B.H., 1988, Medullary and spinal efferents of the pedunculopontine tegmental nucleus and adjacent mesopontine tegmentum in the rat, J.Comp. Neurol., 269:315.PubMedCrossRefGoogle Scholar
  40. Rye, D.B., Saper, C.B., Lee, H.J., and Wainer, B.H., 1987, Pedunculopontine tegmental nucleus of the rat: cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum, J.Comp. Neurol., 259:483.PubMedCrossRefGoogle Scholar
  41. Saper, C.B., 1987, Diffuse cortical projection systems: anatomical organization and role in cortical function, in: “Handbook of Physiology. Section 1: The Nervous System. Volume V. Higher Functions of the Brain, Part 2.”, V.B. Mountcastle, F. Plum and S.R. Geiger, eds., American Physiological Society, Bethesda, Md, p. 169.Google Scholar
  42. Saper, C.B., and Loewy, A.D., 1982, Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry. Brain Res, 252:367.PubMedCrossRefGoogle Scholar
  43. Satoh, K., and Fibiger, H.C., 1986, Cholinergic neurons of the laterodorsal tegmental nucleus: Efferent and afferent connections, J.Comp. Neurol., 253:277.PubMedCrossRefGoogle Scholar
  44. Scarnati, E., Prioria, A., Campana, E., and Pacitti, C., 1986, A microiontophoretic study of the nature of the putative synaptic neurotransmitter involved in the pedunculopontine substantia nigra pars compacta excitatory pathway in the rat, Exp. Brain Res., 62:470.PubMedCrossRefGoogle Scholar
  45. Scarnati, E., Prioria, A., DiLoreto, S., and Pacitti, C., 1986, The reciprocal electrophysiological influence between the nucleus tegmenti pedunculopontinus and the substantia nigra in normal and decorticated rats. Brain Res., 423:116.CrossRefGoogle Scholar
  46. Scherer-Singler, U., Vincent, S.R., Kimura, H., and McGeer, E.G., 1983, Demonstration of a unique population of neurons with NADPH diaphorase histochemistry, Neurosci. Meth., 9:229.CrossRefGoogle Scholar
  47. Semba, K., Reiner, P.B., McGeer, E.G., and Fibiger, H.C., 1986, Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat, Compt Neurol., 267:433.CrossRefGoogle Scholar
  48. Semba, K., Reiner, P.B., McGeer, E.G., and Fibiger, H.C., 1986, Brainstem projecting neurons in the rat basal forebrain: Neurochemical, topographical and physiological distinctions from cortically projecting cholinergic neurons. Brain. Res. Bull., 22:501.CrossRefGoogle Scholar
  49. Semba, K., 1991, The cholinergic basal forebrain: A critical role in cortical arousal, in: “The Basal Forebrain: Anatomy to Function”, T.C. Napier, P.W. Kalivas, and I. Hanin, eds., Plenum Press, New York, (in press).Google Scholar
  50. Sofroniew, M.V., Priestly, J.V., Consolazione, A., Eckenstein, F., and Cuello, A.C., 1985, Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry. Brain Res., 329:213.PubMedCrossRefGoogle Scholar
  51. Standaert, D.G., Saper, C.B., Rye, D.B., and Wainer, B.H., 1986, Colocalization of atriopeptin like immunoreactivity with choline acetyltransferase and substance P like immunoreactivity in the pedunculopontine and laterodorsal tegmental nuclei in the rat. Brain Res., 382:163.PubMedCrossRefGoogle Scholar
  52. Steriade, M., and McCarley, R. W., 1990, “Brainstem Control of Wakefulness and Sleep”, Plenum Press, New York.Google Scholar
  53. Sugimoto, T., and Hattori, T., 1984, Organization and efferent projections of nucleus tegmenti pedunculopontinus pars compacta with special reference to its cholinergic aspects, Neurosci., 11:931.CrossRefGoogle Scholar
  54. Sutin, E.L., and Jacobowitz, D.M., 1988, Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area, J. Comp, Neurol, 270:243.CrossRefGoogle Scholar
  55. Vincent, S.R., and Satoh, K., 1984, Corticotropin releasing factor (CRF) immunoreactivity in the dorsolateral pontine tegmentum: further studies on the micturition reflex system. Brain Res., 308:387.PubMedCrossRefGoogle Scholar
  56. Vincent, S.R., Satoh, K., Armstrong, D.M., and Fibiger, H.C., 1983, NADPH- diaphorase: A selective histochemical marker for the cholinergic neurons of the pontine reticular formation, Neurosci. Lett., 43:31.PubMedCrossRefGoogle Scholar
  57. Vincent, S.R., Satoh, K., Armstrong, D.M., Panula, P., Vale, W., and Fibiger, H.C., 1986, Neuropeptides and NADPH- diaphorase activity in the ascending cholinergic reticular system of the rat, Neurosci, 17:167.CrossRefGoogle Scholar
  58. Wilcox, K.S., Grant, S.J., Burkhardt, B., and Christoph, G.R., 1989, Electrophysiological properties of lateral dorsal tegmental neurons in vitro. Brain Res. Bull., 22:557.PubMedCrossRefGoogle Scholar
  59. Yamano, M., and Tohyama, M., 1987, Afferent and efferent enkephalinergic systems of the tegmental nuclie of Gudden in the rat: an immunocytochemical study. Brain Resw., 408:22.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • J. R. Clements
    • 1
  • D. D. Toth
    • 1
  • D. A. Highfield
    • 1
  • S. J. Grant
    • 1
  1. 1.School of Life and Health Sciences and Department of PsychologyUniversity of DelawareNewarkUSA

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