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GABA as a Transmitter in the Central Nervous System of Vertebrates

  • J. Storm-Mathisen
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 11)

Summary

The topographical and subcellular distribution of GAD has been studied in Deiters’ nucleus, the cerebellum, hippocampus and substantia nigra, and the effect of lesions of nerve pathways has been examined. The results showed that GAD is localized in Purkinje cells and probably also in neurones confined to the cerebellar cortex. In the hippocampus GAD is localized in intrinsic neurones, some of which are likely to be the basket cells. In the substantia nigra GAD is localized in nerve terminals the density of which may be highest in the pars compacta. The axons to which these terminals belong probably originate in the neostriatum or globus pallidus.

All the available data put together go far towards proving that GABA is the transmitter of the Purkinje cells. They indicate that the same is true for the cerebellar stellate, basket and Golgi cells, the basket cells of the hippocampus, local inhibitory neurones in the cerebral cortex and the striato-nigral fibres. These may be but a small selection of all GABAneurones.

Keywords

Purkinje Cell Nerve Terminal Cerebellar Cortex Globus Pallidus Mossy Fibre 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AChE

acetylcholinesterase

ChAc

choline acetyltransferase

DOPA

dihydroxyphenylalanine

GABA

γ-aminobutyric acid

GAD

glutamate decarboxylase

IPSP

inhibitory postsynaptic potential

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References

  1. Albers, R. W., and R. O. Brady: The distribution of glutamate decarboxylase in the nervous system of the rhesus monkey. J. biol. Chem. 234, 926 to 928 (1959).PubMedGoogle Scholar
  2. Andersen, P., J. C. Eccles, and Y. Loyning: Pathway of postsynaptic inhibition in the hippocampus. J. Neurophysiol. 27, 608–619 (1964).PubMedGoogle Scholar
  3. Andersen, P., J. C. Eccles, Y. Loyning, and P. E. Voorhoeve: Strychnine resistant inhibition in the brain. Nature (London) 200, 843 (1963).CrossRefGoogle Scholar
  4. Andersen, P., B. Holmqvist, and P. E. Voorhoeve: Entorhinal activation of dentate granule cells. Acta physiol. scand. 66, 448–460 (1966).PubMedCrossRefGoogle Scholar
  5. Baxter, C. F.: The nature of y-aminobutyric acid. In: Handbook of Neurochemistry (Lajtha, A., ed.), Vol. III, pp. 289–353. New York: Plenum Press. 1970.Google Scholar
  6. Bisti, S., G. losif, B. F. Marchesi, and P. Strata: Pharmacological properties of inhibitions in the cerebellar cortex. Exp. Brain Res. 14, 24–37 (1971).PubMedCrossRefGoogle Scholar
  7. Bloom, F. E., and L. L. Iversen: Localizing 3H-GABA in nerve terminals of rat cerebral cortex by electron microscopic autoradiography. Nature (London) 229, 628–630 (1971).CrossRefGoogle Scholar
  8. Bradford, H. F.: Metabolic response of synaptosomes to electrical stimulation: Release of amino acids. Brain Res. 19, 239–247 (1970).PubMedCrossRefGoogle Scholar
  9. Bruggencate, G. ten., and I. Engberg: Effects of GABA and related amino acids on neurons in Deiters’ nucleus. Brain Res. 14, 533–536 (1969 a).PubMedCrossRefGoogle Scholar
  10. Bruggencate, G. ten., and I. Engberg: The effect of strychnine on inhibition in Deiters’ nucleus induced by GABA and glycine. Brain Res. 14, 536–539 (1969 b).PubMedCrossRefGoogle Scholar
  11. Chalmers, A., E. G. McGeer, V. Wickson, and P. L. McGeer: Distribution of glutamic acid decarboxylase in the brains of various mammalian species. Comp. gen. Pharmacol. 1, 385–390 (1970).Google Scholar
  12. Csillik, B., A. M. Gerebtzoff, J. Kiss, and E. Knyihar: Zur Histochemie der limbischen Hemmung. Zytochemische und autoradiographische Untersuchungen über die Lokalisation der Enzyme des Gamma-aminoButtersäure-Stoffwechsels im Hippocampus der Ratte. Histochemie 28, 38–54 (1971).PubMedCrossRefGoogle Scholar
  13. Curtis, D. R., A. W. Duggan, and D. Felix: GABA and inhibition of Deiters’ neurons. Brain Res. 23, 117–120 (1970a).PubMedCrossRefGoogle Scholar
  14. Curtis, D. R., A. W. Duggan, D. Felix, and G. A. R. Johnston: GABA, bicuculline, and central inhibition. Nature (London) 226, 1222–1224 (1970 b).PubMedCrossRefGoogle Scholar
  15. Curtis, D. R., A. W. Duggan, D. Felix, and G. A. R. Johnston: Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Res. 32, 69–96 (1971 a).PubMedCrossRefGoogle Scholar
  16. Curtis, D. R., A.W. Duggan, D. Felix, G.A.R. Johnston, and H. McLennan: Antagonism between bicuculline and GABA in the cat brain. Brain Res. 33, 57–73 (1971 b).PubMedCrossRefGoogle Scholar
  17. Curtis, D. R., D. Felix, and H. McLennan: GABA and hippocampal inhibition. Brit. J. Pharmacol. 40, 881–883 (1970).Google Scholar
  18. Dahlström, A., and K. Fuxe: Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, Suppl. 232, 1–55 (1964).Google Scholar
  19. Davidoff, R. A.: Gamma-aminobutyric acid antagonism and presynaptic inhibition in the frog spinal cord. Science 175, 331–333 (1972).PubMedCrossRefGoogle Scholar
  20. Davidson, N., and C. A. P. Southwick: Amino acids and presynaptic inhibition in the rat cuneate nucleus. J. Physiol. (London) 219, 689–708 (1971).Google Scholar
  21. De Groat, W. C.: GABA-depolarization of a sensory ganglion: Antagonism by picrotoxin and bicuculline. Brain Res. 38, 429–432 (1972).PubMedCrossRefGoogle Scholar
  22. Dreifuss, J. I., J. S. Kelly, and K. Krnjevic: Cortical inhibition and 2’-amino-butyric acid. Exp. Brain Res. 9, 137–154 (1969).PubMedCrossRefGoogle Scholar
  23. Eccles, J. C., M. Ito, and J. Szenta’gothai: The Cerebellum as a Neuronal Machine, 335 pp. Berlin-Heidelberg-New York: Springer. 1967.Google Scholar
  24. Ehinger, B., and B. Falck: Autoradiography of some suspected neurotransmitter substances: GABA, glycine, glutamic acid, histamine, dopamine, and L-DOPA. Brain Res. 33, 157–172 (1971).PubMedCrossRefGoogle Scholar
  25. Fahn, S., and L. J. Côté: Regional distribution of gamma-aminobutyric acid (GABA) in brain of the Rhesus monkey. J. Neurochem. 15, 209 to 213 (1968).PubMedCrossRefGoogle Scholar
  26. Fonnum, F.: The distribution of glutamate decarboxylase and aspartate transaminase in subcellular fractions of rat and guinea-pig brain. Biochem. J. 106, 291–298 (1968).Google Scholar
  27. Fonnum, F.: Application of microchemical analysis and subcellular fractionation techniques to the study of neurotransmitters in discrete areas of mammalian brain. In: Studies in neurotransmitters at the synaptic level (Costa, E., and L. L. Iversen, eds.). Adv. biochem. Psychopharmacol. 6, pp. 75–88. New York: Raven Press. 1972 a.Google Scholar
  28. Fonnum, F.: Localization of cholinergic and y-aminobutyric acid containing pathways in brain. In: Metabolic compartmentation in the brain (Balâzs, R., and J. Grenier, eds.), pp. 245–257. London: Macmillan. 1972 b.Google Scholar
  29. Fonnum, F., J. Storm-Mathisen, and F. Walberg: Glutamate decarboxylase in inhibitory neurones. A study of the enzyme in Purkinje cell axons and boutons in the cat. Brain Res. 20, 259–275 (1970).PubMedCrossRefGoogle Scholar
  30. Fonnum, F., and F. Walberg: An estimation of the concentration of y-aminobutyric acid and glutamate decarboxylase in the inhibitory Purkinje axon terminals in the cat. Brain Res. 54, 115–127 (1973).PubMedCrossRefGoogle Scholar
  31. Gottesfeld, Z., K. Krnjevie, and R. J. Reiffenstein: Penetration of circulating GABA into long-isolated cortical slabs. Canad. J. Physiol. Pharmacol. 49, 70–78 (1971).CrossRefGoogle Scholar
  32. Graham, L. T., jr., C. F. Baxter, and R. N. Lolley: In vivo influence of light or darkness on the GABA system in the retina of the frog (Rana pipiens). Brain Res. 20, 379–388 (1970).PubMedCrossRefGoogle Scholar
  33. Grofovíi, I., and E. Rinvik: An experimental electron microscopic study on the strionigral projection in the cat. Exp. Brain Res. 11, 249–262 (1970).CrossRefGoogle Scholar
  34. Haber, B., K. Kuriyama, and E. Roberts: L-glutamic acid decarboxylase: A new type in glial cells and human brain gliomas. Science 168, 589–599 (1970a).CrossRefGoogle Scholar
  35. Haber, B., K. Kuriyama, and E. Roberts: An anion stimulated L-glutamic acid decarboxylase in non-neural tissues: Occurrence and subcellular localization in mouse kidney and developing chick embryo brain. Biochem. Pharmacol. 19, 1119–1136 (1970b).CrossRefGoogle Scholar
  36. Hirsch, H., and E. Robins: Distribution of y-aminobutyric acid in the layers of the cerebral and cerebellar cortex. Implications for its physiological role. J. Neurochem. 9, 63–70 (1962).PubMedCrossRefGoogle Scholar
  37. Hökfelt, T., and A. Ljungdahl: Uptake of (3H) noradrenaline and 7-(3H) aminobutyric acid in isolated tissues of rat: An autoradiographic and fluorescence microscopic study. In: Histochemistry of nervous transmission (Eränkö, O., ed.). Progr. Brain Res. 34, 87–102 (1971).Google Scholar
  38. Hökfelt, T., and A. Ljungdahl: Autoradiographic identification of cerebellar and cerebral cortical neurons accumulating labelled gamma-aminobutyric acid (3H-GABA). Exp. Brain Res. 14, 354–362 (1972).PubMedCrossRefGoogle Scholar
  39. Huffman, R. D., and L. S. McFadin: Suppression of presynaptic inhibition and cerebellar disfacilitation by bicuculline. Life Sci. Part. I, 11, 113–121 (1972).Google Scholar
  40. Ito, M., and M. Yoshida: The origin of cerebellar-induced inhibition of Deiters’ neurons. I. Monosynaptic initiation of the inhibitory post-synaptic potentials. Exp. Brain Res. 2, 330–349 (1966).PubMedGoogle Scholar
  41. Ito, M., M. Yoshida, and K. Obata: Monosynaptic inhibition of the intra-cerebellar nuclei induced from the cerebellar cortex. Experientia (Basel) 20, 575–576 (1964).CrossRefGoogle Scholar
  42. Iversen, L. L., and F. E. Bloom: Studies on the uptake of 3H-GABA and (3H) glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography. Brain Res. 41, 131–143 (1972).PubMedCrossRefGoogle Scholar
  43. Iversen, L. L., and G. A. R. Johnston: GABA uptake in rat central nervous system: Comparison of uptake in slices and homogenates and the effects of some inhibitors. J. Neurochem. 18, 1939–1950 (1971).PubMedCrossRefGoogle Scholar
  44. Iversen, L. L., J. F. Mitchell, and V. Srinivasan: The release of y-aminobutyric acid during inhibition in the cat visual cortex. J. Physiol. (London) 212, 519–534 (1971).Google Scholar
  45. Iversen, L. L., and M. J. Neal: The uptake of (3H) GABA by slices of rat cerebral cortex. J. Neurochem. 15, 1141–1149 (1968).PubMedCrossRefGoogle Scholar
  46. Jansen, J., and A. Brodai: Experimental studies on the intrinsic fibres of the cerebellum. II. Corticonuclear projection. J. comp. N. 73, 267–321 (1940).Google Scholar
  47. Jansen, J., and A. Brodai: Handbuch der mikroskopischen Anatomie des Menschen. IV. Nervensystem. Das Kleinhirn, 323 pp. Berlin-GöttingenHeidelberg: Springer. 1958.Google Scholar
  48. Jasper, H. H., and I. Koyama: Rate of release of amino acids from the cerebral cortex in the cat as affected by brainstem and thalamic stimulation. Canad. J. Physiol. Pharmacol. 47, 889–905 (1969).CrossRefGoogle Scholar
  49. Killam, K. F., S. R. Dasgupta, and E. K. Killam: Studies of the action of convulsant hydrazides as vitamin Bß antagonists in the central nervous system. In: Inhibition in the nervous system and gamma-aminobutyric acid (Roberts, E., ed.), pp. 302–316. Oxford: Pergamon. 1960.Google Scholar
  50. Kim, J. S., Y. Okada, R. Hassler, and I. J. Bak: The role of y-aminobutyric acid (GABA) in extrapyramidal motor system. 2. Some evidence for the existence of a type of GABA-rich strionigral neurons. Exp. Brain Res. 14, 95–104 (1971).PubMedCrossRefGoogle Scholar
  51. Kuhar, M. J., R. H. Roth, and G. K. Aghajanian: Choline uptake into synaptosomes from the hippocampus: Reduction after electrolytic destruction of the medial septal nucleus. Fed. Proc. 31, 516 Abs. (1972).Google Scholar
  52. Kuriyama, K., B. Haber, B. Sisken, and E. Roberts: The y-aminobutyric acid system in rabbit cerebellum. Proc. nat. Acad. Sci. (Washington) 55, 846–852 (1966).CrossRefGoogle Scholar
  53. Kuriyama, K., B. Sisken, B. Haber, and E. Roberts: The y-aminobutyric acid system in rabbit retina. Brain Res. 9, 165–168 (1968).PubMedCrossRefGoogle Scholar
  54. Kuriyama, K., H. Weinstein, and E. Roberts: Uptake of y-aminobutyric acid by mitochondrial and synaptosomal fractions from mouse brain. Brain Res. 16, 479–492 (1969).PubMedCrossRefGoogle Scholar
  55. Lain, D. M. K., and L. Steinman: The uptake of (y-3H) aminobutyric acid in the goldfish retina. Proc. nat. Acad. Sci. (Washington) 68, 2777–2781 (1971).CrossRefGoogle Scholar
  56. Lewis, P. R., C. C. D. Shute, and A. Silver: Confirmation from choline acetylase analyses of a massive cholinergic innervation to the rat hippocampus. J. Physiol. (London) 191, 215–224 (1967).Google Scholar
  57. Lorento de Nó, R.: Studies on the structure of the cerebral cortex. II. Continuation of the study of the ammonic system. J. Psychol. Neurol. (Leipzig) 46, 113–117 (1934).Google Scholar
  58. Lowry, O. H.: The quantitative histochemistry of the brain. J. Histochem. Cytochem. 1, 420–428 (1953).PubMedCrossRefGoogle Scholar
  59. McGeer, P. L., E. G. McGeer, J. A. Wada, and E. Jung: Effects of globus pallidus lesions and Parkinson’s disease on brain glutamic acid decarboxylase. Brain Res. 32, 425–431 (1971).PubMedCrossRefGoogle Scholar
  60. Mitchell, J. F., and V. Srinivasan: Release of 3H-y-aminobutyric acid from the brain during synaptic inhibition. Nature (London) 224, 663–666 (1969).CrossRefGoogle Scholar
  61. Mugnaini, E., and F. Walberg: An experimental electronmicroscopical study on the mode of termination of cerebellar corticovestibular fibres in the cat lateral vestribular nucleus (Deiters’ nucleus). Exp. Cell Res. 4, 212–236 (1967).Google Scholar
  62. Nafstad, P. H. J., and T. W. Blackstad: Distribution of mitochondria in pyramidal cells and boutons in hippocampal cortex. Z. Zellforsch. 73, 234–245 (1966).PubMedCrossRefGoogle Scholar
  63. Neal, M. J., and L. L. Iversen: Subcellular distribution of endogenous and (3H) y-aminobutyric acid in rat cerebral cortex. J. Neurochem. 16, 1245–1252 (1969).PubMedCrossRefGoogle Scholar
  64. Obata, K., and S. M. Highstein: Blocking by picrotoxin of both vestibular inhibition and GABA action on rabbit oculomotor neurons. Brain Res. 18, 531–538 (1970).CrossRefGoogle Scholar
  65. Obata, K., M. Ito, R. Ochi, and N. Sato: Pharmacological properties of the postsynaptic inhibition by Purkinje cell axons and the action of y-aminobutyric acid on Deiters’ neurons. Exp. Brain Res. 4, 43–57 (1967).PubMedCrossRefGoogle Scholar
  66. Obata, K., and K. Takeda: Release of y-aminobutyric acid into the fourth ventricle induced by stimulation of the cat’s cerebellum. J. Neurochem. 16, 1043–1047 (1969).PubMedCrossRefGoogle Scholar
  67. Obata, K., K. Takeda, and H. Shinozaki: Further study on pharmacological properties of the cerebellar-induced inhibition of Deiters’ neurones. Exp. Brain Res. 11, 327–342 (1970).PubMedCrossRefGoogle Scholar
  68. Otsuka, M., L. L. Iversen, Z. W. Hall, and E. A. Kravitz: Release of gammaaminobutyric acid from inhibitory nerves of lobster. Proc. nat. Acad. Sci. (Washington) 56, 1110–1115 (1966).CrossRefGoogle Scholar
  69. Otsuka, M., K. Obata, Y. Miyata, and O. Tanaka: Measurement of y-aminobutyric acid in isolated nerve cells of cat central nervous system. J. Neurochem. 18, 287–295 (1971).PubMedCrossRefGoogle Scholar
  70. Phillis, J. W.: Cholinergic mechanisms in the cerebellum. Brit. med. Bull. 21, 26–29 (1965).Google Scholar
  71. Precht, W., and M. Yoshida: Blockage of caudate-evoked inhibition of neurons in the substantia nigra by picrotoxin. Brain Res. 32, 229–233 (1971).PubMedCrossRefGoogle Scholar
  72. RamónyCajal, S.: The Structure of Ammon’s Horn (translated by Kraft, L. M.). Springfield, Ill.: Thomas. 1968.Google Scholar
  73. Roberts, E., and D. G. Simonsen: Some properties of L-glutamic decarboxylase in mouse brain. Biochem. Pharmacol. 12, 113–134 (1963).PubMedCrossRefGoogle Scholar
  74. Roberts, E., J. Wein, and D. G. Simonsen: y-Aminobutyric acid (7ABA), vitamin Bs, and neuronal function.—A speculative synthesis. Vitamins and Hormones 22, 503–559 (1964).PubMedCrossRefGoogle Scholar
  75. Storm-Mathisen, J.: Glutamate decarboxylase in the rat hippocampal region after lesions of the afferent fibre systems. Evidence that the enzyme is localized in intrinsic neurones. Brain Res. 40, 215–235 (1972).PubMedCrossRefGoogle Scholar
  76. Storm-Mathisen, J., and F. Fonnum: Quantitative histochemistry of glutamate decarboxylase in the rat hippocampal region. J. Neurochem. 18, 1105–1111 (1971).PubMedCrossRefGoogle Scholar
  77. Sze, P. Y., and R. A. Lovell: A reexamination of the effect of thiosemicarbazide on brain GABA and glutamic decarboxylase in vivo. Life Sci. Part 1, 9, 889–899 (1970).Google Scholar
  78. Walberg, F., and J. Jansen: Cerebellar corticovestibular fibres in the cat. Exp. Neurol. 3, 32–52 (1961).PubMedCrossRefGoogle Scholar
  79. Walberg, F., and J. Jansen: Cerebellar corticonuclear projection studied experimentally with silver impregnation methods. J. Hirnforsch. 6, 338–354 (1964).Google Scholar
  80. Wofsey, A. R., M. J. Kuhar, and S. Snyder: A unique synaptosomal fraction, which accumulates glutamic and aspartic acids, in brain tissue. Proc. nat. Acad. Sci. (Washington) 68, 1102–1106 (1971).CrossRefGoogle Scholar
  81. Woodward, D. J., B. J. Hoffer, G. R. Siggins, and A. P. Oliver: Inhibition of Purkinje cells in the frog cerebellum. II. Evidence for GABA as the inhibitory transmitter. Brain Res. 33, 91–100 (1971).PubMedCrossRefGoogle Scholar
  82. Yoshida, M., and W. Precht: Monosynaptic inhibition of neurons of the substantia nigra by caudate-nigral fibres. Brain Res. 32, 225–228 (1971).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • J. Storm-Mathisen
    • 1
  1. 1.Division for ToxicologyNorwegian Defence Research EstablishmentKjellerNorway

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