Development of GABA-Ergic System in Rat Visual Cortex

  • J. R. Wolff
  • V. J. Balcar
  • T. Zetzsche
  • H. Böttcher
  • D. E. Schmechel
  • B. M. Chronwall
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 181)


In 1956 Eugene Roberts stated, “Perhaps the most difficult question to answer would be whether the presence in the grey matter of the central nervous system of uniquely high concentrations of γ-aminobutyric acid and the enzyme which forms it from glutamic acid has a direct or indirect connection to conduction of the nerve impulse in this tissue”. Thirty years later γ-aminobutyrate (GABA, 4-aminobutyrate) is universally accepted as the major inhibitory synaptic transmitter. This review is trying to explore its additional roles, beyond a mediation of synaptic transmission. Specifically, we are examining a possibility that GABA, on account of its characteristic chemical properties in interaction with excitable membranes, mediates communication among differentiating neurons, thus influencing expression of neuronal functions, making the orderly development of synaptic connections possible.


Occipital Cortex Numerical Density Cortical Plate Ontogenetic Development Gaba Uptake 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, P.R., and Brown, D.A., 1975, Action of γ-aminobutyric acid on the sympathetic ganglion cells, J. Physiol., London, 250: 85–120.Google Scholar
  2. Adams, J.C., 1981, Heavy metal intensification of DAB-based HRP reaction product, J. Histochem. Cytochem., 19: 755.Google Scholar
  3. Anvengine, J.B., Jr., and Sidman, R.L., 1961, Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse, Nature, 192: 766–768.Google Scholar
  4. Bahr, S. and Wolff, J.R., Postnatal development and loss of axosomatic synapses in the rat visual cortex. Morphogenesis and quantitative evaluation of type 1 and type 2 synapses (submitted).Google Scholar
  5. Balcar, V.J., Mark, J., Borg, J., and Mandel, P., 1979, High affinity uptake of γ-aminobutyric acid in cultured glial and neuronal cells, Neurochem. Res., 4: 339–354.PubMedCrossRefGoogle Scholar
  6. Balcar, V.J., and Hauser, K.L., 1982, Development of uptake of γ-aminobutyrate in cultured neurons, 12th Intern. Congr. Biochem. (Abstract), 95.Google Scholar
  7. Balcar, V.J., Dammasch, I., and Wolff, J.R., 1983, Is there a non-synaptic component in the K+-stimulated release of GABA in the developing rat cortex? Dev. Brain Res., 10: 309–311.CrossRefGoogle Scholar
  8. Berry, M., and Rogers, A.W., 1965, The migration of neuroblasts in the developing cerebral cortex, J. Anat., 99: 691–709.PubMedGoogle Scholar
  9. Berry, M., 1982, Cellular differentiation: Development of dendritic arborizations under normal and experimentally altered conditions, in: “Development and Modifiability of the Cerebral Cortex”, P. Rakic and P.S. Goldman-Rakic, eds., Neurosci. Res. Progr. Bull., 20: 451–461.Google Scholar
  10. Bowery, N.G., and Brown, D.A., 1972, γ-aminobutyric acid uptake by sympathetic ganglia, Nature, 238: 89–91.CrossRefGoogle Scholar
  11. Chronwall, B.M., and Wolff, J.R., 1978a, Classification and location of neurons taking up 3H-GABA in the visual cortex of rats, in:“Amino Acids as Chemical Transmitters”, Plenum Press, New York, pp. 297–303.CrossRefGoogle Scholar
  12. Chronwall, B.M., and Wolff, J.R., 1978b, Aspects on the development on non-pyramidal neurons in the neocortex of rat, Zoon, 6: 145–148.Google Scholar
  13. Chronwall, B.M., and Wolff, J.R., 1980, Prenatal and postnatal development of GABA-accumulating cells in the occipital cortex of rat, J. Comp. Neurol., 190: 187–208.Google Scholar
  14. Costa, E., Di Chiara, G., and Gessa, G.L., ed., 1981, “GABA and Benzodiazepine Receptors”, Adv. Biochem. Pharmaco1., 26, Raven Press, New York.Google Scholar
  15. Coyle, J.T., and Enna, S.J., 1976, Neurochemical aspects of the ontogenesis of GABA-ergic neurons in the rat brain, Brain Res., 111: 119–133.PubMedCrossRefGoogle Scholar
  16. Coyle, J.T., 1982, Development of neurotransmitters in the neocortex, in: “Development and Modifiability of the Cerebral Cortex”, P. Rakic and P.S. Goldman-Rakic, eds., Neurosci. Res. Progr. Bull. 20: 479–492.Google Scholar
  17. Davies, L.P., Johnston, G.A.R., and Stephanson, A.L., 1975, Postnatal changes in the potassium-stimulated, calcium-dependent release of radioactive GABA and glycine from slices of rat central nervous tissue, J. Neurochem., 387–392.Google Scholar
  18. Emson, P.C., and Hunt, S.P., 1981, Anatomical chemistry of the cerebral cortex, in: “The Organization of the Cerebral Cortex”, F.O. Schmitt, F.G. Worden, G. Adelmann, S.G. Dennis, eds., MIT-Press, Cambridge, Massachusetts, and London, England, pp. 325–345.Google Scholar
  19. Fagg, G.E., and Lane, J.D., 1979, The uptake and release of putative amino acid transmitters, Neuroscience, 4: 1015–1036.PubMedCrossRefGoogle Scholar
  20. Gallyas, F., Görcs, T., and Merchenthal, I., 1982, High-grade intensification of the end product of the diaminobenzidine reaction for peroxidase histochemistry, J. Histochem. Cytochem., 30: 183–184.PubMedCrossRefGoogle Scholar
  21. Hauser, K.L., and Heid, J., 1978, Morphology and biochemistry of rat cortical neurons in dissociated cell culture, Proc. Eur. Soc. Neurochem., 1: 503.Google Scholar
  22. Hauser, K.L., Balcar, V.J., and Bernasconi, R., 1980, Development of GABA neurons in dissociated cell culture of rat cerebral cortex, in: “GABA Neurotransmission”, H. Lal, ed., Brain Res. Bull. 5, suppl. 2: 37–41.Google Scholar
  23. His, W., 1904, Die Entwicklung des menschlichen Gehirns während der ersten Monate, Hirzel Verlag’, Leipzig.Google Scholar
  24. Hökfelt, T., and Ljungdahl, A., 1972, Autoradiographic identific-action of cerebral and cerebellar cortical neurons accumulating labeled gamma-aminobutyric acid (3H-GABA). Exp. Brain Res., 14: 354–362.PubMedCrossRefGoogle Scholar
  25. Horton, R.W., 1980, GABA and seizures induced by inhibition of glutamic acid decarboxylase, in: GABA Neurotransmission”, H. Lal, ed., Brain Res. Bull. 5, suppl. 2: 605–608.Google Scholar
  26. Houser, C.R., Lee, M., and Vaughn, J.E., 1983, Immunocytochemical localization of glutamic acid decarboxylase in normal and de-afferented superior colliculus: Evidence for reorganization of γ-aminobutyric acid synapses. J. Neurosci. 3: 2030–2042.PubMedGoogle Scholar
  27. Iversen, L.L., and Neal, M.J., 1968, The uptake of 3H-GABA by slices of rat cerebral cortex, J. Neurochem., 15: 1141–1149.PubMedCrossRefGoogle Scholar
  28. Iversen, L.L., and Johnston, G.A.R., 1971, 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.PubMedCrossRefGoogle Scholar
  29. Iversen, L.L., and Kelly, J.S., 1975, Uptake and metabolism of γ-aminobutyric acid by neurons and glial cells, Biochem. Pharmacol., 24: 933–938.PubMedCrossRefGoogle Scholar
  30. Jacobson, M., 1978, “Developmental Neurobiology”, Plenum Press, New York.Google Scholar
  31. Johnston, G.A.R., and Davies, L.P., 1974, Postnatal changes in the high affinity uptake of glycine and GABA in the rat central nervous system. J. Neurochem., 22: 101–105.PubMedCrossRefGoogle Scholar
  32. Johnston, G.A.R., 1977, Effects of calcium on the potassium-stimulated release of radioactive β-alanine and γ-aminobutyric acid from slices of rat cerebral cortex and spinal cord, Brain Res., 121: 179–181.PubMedCrossRefGoogle Scholar
  33. Jóo, F., Dames, W., and Wolff, J.R., 1979, Effect of prolonged sodium bromid administration on the fine structure of dendrites in the superior ganglion of adult rat. Progr. in Brain Res., 51: 109–115.CrossRefGoogle Scholar
  34. Katz, R.I., Chase, T.N., and Kopin, I.J., 1969, Effect of ions on stimulus-induced release of amino acids from mammalian brain slices. J. Neurochem. 16: 961–964.PubMedCrossRefGoogle Scholar
  35. Levi, G., and Raiteri, M., 1974, Exchange of neurotransmitter amino acids at nerve endings can stimulate high-affinity uptake. Nature, 250: 735–737.PubMedCrossRefGoogle Scholar
  36. Martin, D.L., 1976, Carrier-mediated transport and removal of GABA from synaptic regions, in: “GABA in Nervous System Function”, E. Roberts, T.N. Chase, D.B. Tower, eds., Raven Press, New York, pp. 347–386.Google Scholar
  37. Meier, E., Drejer, J., and Schousboe, A., 1983, Trophic actions of GABA on the development of physiologically active GABA receptors, in: “CNS-Receptors from Molecular Pharmacology to Behaviour”, P. Mandel, F.V. DeFeudis, eds., Raven Press, New York, Adv. Biochem. Psychopharmacol. 37: 47–58.Google Scholar
  38. Neal, M.J., and Bowery, N.G., 1977, Cis-3-aminocyclohexane-carboxylic acid: a substrate for the neuronal GABA transport system, Brain Res., 138: 169–174.PubMedCrossRefGoogle Scholar
  39. Parnavelas, J.G., and Uylings, H.B.M., 1980, Growth of non-pyramidal neurons in the visual cortex of the rat: A morphometric study, Brain Res., 193: 373–382.PubMedCrossRefGoogle Scholar
  40. Raedler, A., and Sievers, J., 1975, The development of the visual system of the albino rat, Adv. Anat. Embryol. Cell Biol., 50, Springer, Berlin-Heidelberg-New York, pp. 88.CrossRefGoogle Scholar
  41. Rakic, P., 1972, Mode of cell migration to the superficial layers of fetal monkey neocortex, J. Comp. Neurol., 145: 61–84.PubMedCrossRefGoogle Scholar
  42. Rakic, P., 1974, Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition, Science, 183: 425–427.PubMedCrossRefGoogle Scholar
  43. Redburn, D.A., Broome, D., Ferkany, J., and Enna, S.J., 1978, Development of rat brain uptake and calcium-dependent release of GABA, Brain Res., 152: 511–519.PubMedCrossRefGoogle Scholar
  44. Ribak, C.E., 1978, Aspinous and sparsely-spinous stellate neurons in the visual cortex of rats contain glutamic acid decarboxylase, J. Neurocytol., 7: 461–478.PubMedCrossRefGoogle Scholar
  45. Rickmann, M., Chronwall, B.M., and Wolff, J.R., 1977, On the development of non-pyramidal neurons and axons outside the cortical plate: The early marginal zone as a pallial anlage, Anat. Embryol., 151: 285:307.PubMedCrossRefGoogle Scholar
  46. Rickmann, M., and Wolff, J.R., 1977, Cytological characteristics of early stages of glial differentiatin in the neocortex, Folia Morphol. 25: 235–239.Google Scholar
  47. Rickmann, M., and Wolff, J.R., Prenatal Gliogenesis in the neopallium of rat. Adv. Anat. Embryol. Cell Biol.(in press).Google Scholar
  48. Seiler, N, and Sarhan, S., 1983, Metabolic routes of GABA formation in chick embryo brain, Neurochem. Intern., 5: 625–633.CrossRefGoogle Scholar
  49. Srinivasan, V., Neal, M.J., and Mitchell, J.F., 1969, The effect of electrical stimulation and high potassium concentrations on the efflux of [3H]γ-aminobutyric acid from brain slices. J. Neurochem., 16: 1235–1244.PubMedCrossRefGoogle Scholar
  50. Taberner, P.V., Pearce, M.J., and Watkins, J.C., 1977, The inhibition of mouse brain glutamate decarboxylase by some structural analogues of L-glutamatic acid, Biochem. Pharmacol., 26: 345–349.PubMedCrossRefGoogle Scholar
  51. Weissmann-Nanopolous, D., Belin, M.F., Didier, M., Aguera, M., Partisani, M., Maitre, M., and Pujol, J.F., 1983, Immuno-histochemical evidence for neuronal and non-neuronal synthesis of GABA in the rat subcommissural organ. Neurochem. Intern., 5: 785–791.CrossRefGoogle Scholar
  52. Wilson, S.H., Schrier, B.K., Farber, J.L., Thompson, E.J., Rosenberg, R.N., Blume, A.J., and Nirenberg, M.W., 1972, Markers for gene expression in cultured cells from the nervous system, J. Biol. Chem., Vol. 247, No. 10, pp. 3159–3169.PubMedGoogle Scholar
  53. Wolff, J.R., 1978, Ontogenetic aspects of cortical architecture: Lamination, in:”Architectonics of the Cerebral Cortex, M.A. Brazier and H. Petsche, eds., Raven Press, New York, pp. 159–173.Google Scholar
  54. Wolff, J.R., Chronwall, B.M., and Rickmann, M., 1978, Morphogenese relations between cell migration and synaptogenesis in the neocortex of rat, in:“Proceeding of the European Society for Neurochemistry”, vol. 1., V. Neuhoff, ed., Verlag Chemie, Weinheim-New York, pp. 158–173.Google Scholar
  55. Wolff, J.R., Jóo, F., and Dames, W., 1978, Plasticity in dendrites shown by continuous GABA administration in superior cervical ganglion of adult rat, Nature, 274: 72–74.PubMedCrossRefGoogle Scholar
  56. Wolff, J.R., Rickmann, M., and Chronwall, B.M., 1979, Axo-glial synapses and GABA-accumulating glial cells in the embryonic neocortex of the rat, Cell Tiss. Res., 201: 239–248.Google Scholar
  57. Wolff, J.R., 1981, Some morphogenetic aspects of the development of the central nervous system, in: “Behavioral Development. The Bielefeld Interdisciplinary Projec”, K. Immelmann, G.W. Barlow, L. Petrinovich and M. Main (eds.), Cambridge University Press, New York, pp. 164–190.Google Scholar
  58. Wolff, J.R., 1981, Evidence for a dual role of GABA as a synaptic transmitter and a promoter of synaptogenesis, in: “Amino Acid Neurotransmitters”, F.V. DeFeudis, P. Mandel, eds., Raven Press, New York, pp. 459–466.Google Scholar
  59. Wolff, J.R., Jóo, F., Dames, W., and Fehér, O., 1981, Neuroplasticity in the superior cervical ganglion as a consequence of long-lasting inhibition, in: “Cellular Analogues of Conditioning and Neural Plasticity”, O. Fehér, F. Joó, eds., Adv. Physiol. Sci., Vol. 36, pp. 1–9.Google Scholar
  60. Wolff, J.R., and Chronwall, B.M., 1982, Axosomatic synapses in the visual cortex of adult rat. A comparison between GABA-accumulating and other neurons, J. Neurocytol., 11: 409–425.PubMedCrossRefGoogle Scholar
  61. Wolff, J.R., and Wagner, G.P., 1983, Selforganization in synaptogenesis: Interaction between the formation of excitatory and inhibitory synapses, in: “Synergetics of the Brain”, E. Basar, H. Flohr, H. Haken and A.J. Mandel, eds., Springer Verlag, Berlin, Heidelberg, New York, Tokio, pp. 50–59.CrossRefGoogle Scholar
  62. Wolff, J.R., Chronwall, B.M., and Rickmann, M., 1983, “Diffuse deposition mode” provides rat visual cortex with non-pyramidal and GABA-ergic neurons, 4th Intern. Congr. Intern. Soc. for Developm. Neurosci., Abstr. p. 54.Google Scholar
  63. Wolff, J.R., Böttcher, H., Zetzsche, T., Oertel, W.H., and Chronwal, B.M., Development of GABA-ergic neurons in rat visual cortex as identified by glutamatedecarboxylase-like immunoreactivity, Neurosci. Lett, (in press).Google Scholar
  64. Wong, P.T., and McGeer, E., 1981, Postnatal changes of GABA-ergic and glutamatergic parameters, Dev. Brain Res. 1: 519–530.CrossRefGoogle Scholar
  65. Wu, J.Y., 1980, Properties of L-glutamate decarboxylase from non-neuronal tissues, in: “GABA Neurotransmission”, H. Lal, ed., Brain Res. Bull., 5, suppl. 2:31–36.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • J. R. Wolff
    • 1
  • V. J. Balcar
    • 1
  • T. Zetzsche
    • 1
  • H. Böttcher
    • 1
  • D. E. Schmechel
    • 2
  • B. M. Chronwall
    • 3
  1. 1.Dept. of AnatomyUniv. of GöttingenGermany
  2. 2.Dept. of Neurol.Duke Univ.DurhamUSA
  3. 3.Exper. Therap. BranchNIHBethesdaUSA

Personalised recommendations