Skip to main content
SpringerLink
Log in

Cerebellar Granule Cells and the Neurobiology of Excitatory Amino Acids

  • Chapter
The Cerebellum Revisited

Abstract

The discovery that the development in the nervous system involves the loss of a significant number of nerve cells in many structures has given one of the deep insights into mechanisms underlying the development of neuronal organization and of the maintenance of nerve cells (for reviews cf. Cowan et al, 1984; Hamburger and Oppenheimer, 1982; Levi-Montalcini, 1982). It seems that during their differentiation nerve cells become dependent on environmental influences for survival. Most of the evidence concerning specific survival requirements relates to target-derived trophic factors, which are available in limited supply; the best characterized example is nerve growth factor (NGF). In addition, it is believed that afferent nerve fibers also exert trophic influences on nerve cells, but hitherto these have received less attention than the target-derived effects (Cunningham, 1982). Our recent studies on cerebellar granule cells have implicated an afferent system, the mossy fibers, as a source of trophic influence at a critical stage of the maturation of these cells (e.g., Balâzs et al, 1988a, b; Gallo et al, 1987a). Here we present observations indicating that this influence is mediated through the stimulatioji of receptors for excitatory amino acids (EAA) on the postsynaptic granule cells and put forward evidence suggesting that such trophic effects are not unique to the cerebellar granule cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Altman, J. (1982): Morphological development of the rat cerebellum and some of its mechanisms. In: The Cerebellum: New Vistas. (S.L. Palay and V. Chan-Palay, eds). Berlin: Springer, pp. 8–49.

    Chapter  Google Scholar 

  • Aruffo, C, Ferszt, R., Hildebrandt, A.G, and Cerwos-Navarro, J. (1987): Low doses of L-monosodium glutamate promote neuronal growth and differentiation in vitro. Dev. Neurosci., 9, 228–239.

    Article  PubMed  CAS  Google Scholar 

  • Asher, P., and Nowak, L. (1987): Electrophysiological studies of NMDA receptors. Trends Neurosci., 10, 284–288.

    Article  Google Scholar 

  • Balâzs, R. (ed), (1990): Plastic and trophic effects of amino acid transmitters in the developing nervous system. Int. J. Dev. Neurosci, 8(1), 345–503.

    Google Scholar 

  • Balâzs, R., Hack, N, and Jørgensen, O.S. (1990a): Selective stimulation of excitatory amino acid receptor subtypes and the survival of cerebellar granule cells in culture: Effect of kainic acid. Neuroscience, 37, 251–258.

    Article  PubMed  Google Scholar 

  • Balâzs, R., Hack, N., and Jørgensen, O.S. (1990b): Interactive effects involving different classes of excitatory amino acid receptors and the survival of cerebellar granule cells in culture. Int. J. Dev. Neurosci, 8, 347–358.

    Article  PubMed  Google Scholar 

  • Balâzs, R., Hack, N., Jørgensen, O.S., and Cotman, C.W. (1989): N-methyl-D-aspartate promotes the survival of cerebellar granule cells: Pharmacological characterization. Neurosci. Lett., 101, 241–246.

    Article  PubMed  Google Scholar 

  • Balâzs, R., Hack, N., Resink, A., Aronica, E., and Van der Valk, J.B.F. (1992): Trophic effect of excitatory amino acids on differentiating granule cells: Involvement of calcium and other second messengers. Mol. Neuropharmacol. 2.

    Google Scholar 

  • Balâzs, R., and Jørgensen, O.S. (1987): Trophic function of excitatory transmitter amino acids. Neuroscience, 22, S41.

    Google Scholar 

  • Balâzs, R, Jørgensen, O.S., and Hack, N. (1988a): Stimulation of the JV-methyl-D-aspartate receptor has a trophic effect on differentiating cerebellar granule cells. Neurosci. Lett., 87, 80–86.

    Article  PubMed  Google Scholar 

  • Balâzs, R., Jørgensen, O.S., and Hack, N. (1988b): N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture. Neuroscience, 27, 437–451.

    Article  PubMed  Google Scholar 

  • Bettler, B., Boulter, J., Hermans-Borgmeyer, I., O’Shea-Greenfeld, A., Deneris, E.S., Moll, C, Borgmeyer, V., Hollmann, M., and Heinemann, S. (1990): Cloning of a novel glutamate receptor subunit, GluR5: Expression in the nervous system during development. Neuron, 5, 583–595.

    Article  PubMed  CAS  Google Scholar 

  • Bock, E., Divac, L, Norrild, B., Thorn, N.A., Torp-Pedersen, C, and Treiman, M. (1982): Synaptic membrane proteins in mammalian brain. Scand. J. Immunol, 15, 223–240.

    Article  Google Scholar 

  • Brenneman, D., Yu, C, and Nelson, P.G (1990) Multi-determinate regulation of neuronal survival: Neuropeptides, excitatory amino acids and bioelectrical activity. Int. J. Dev. Neurosci, 8, 371–378.

    Article  PubMed  CAS  Google Scholar 

  • Carboni, E., and Wojcik, W.J. (1988): Dihydropyridine binding sites regulate calcium influx through specific voltage-sensitive calcium channels in cerebellar granule cells. J. Neurochem., 50, 1279–1286.

    Article  PubMed  CAS  Google Scholar 

  • Choi, D.W. (1987): Glutamate neurotoxicity in cortical cell cultures. J. Neurosci, 7, 357–368.

    PubMed  CAS  Google Scholar 

  • Choi, D.W., Malucci-Gedde, M., and Kriegstein, A.R. (1987): Glutamate neurotoxicity in cortical cell culture. J. Neurosci, 7, 357–368.

    Google Scholar 

  • Cline, H.T., Debski, E.A., and Constantine-Paton, M. (1987): N-methyl-D-aspartate receptor antagonist desegregates eye-specific strips. Proc. Natl. Acad. Sci. USA, 84, 4342–4345.

    Article  PubMed  CAS  Google Scholar 

  • Collingridge, G.L., and Singer, W. (1990): NMDA receptors—their role in long-term potentiation. Pharmacol. Sci, 11, 290–296.

    CAS  Google Scholar 

  • Cotman, C.W., and Monaghan, D.T. (1988): Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. Annu. Rev. Neurosci, 11, 6–80.

    Article  Google Scholar 

  • Courtney, M.J., Lambert, J.J., and Nicholls, D.G. (1990): The interactions between plasma membrane depolarization and glutamate receptor activation in the regulation of cytoplasmic free calcium in cultured cerebellar granule cells. J. Neurosci, 10, 3873–3879.

    PubMed  CAS  Google Scholar 

  • Cowan, W.M., Fawcett, J.W., O’Leary, D.D.M., and Stanfleld, B.B. (1984): Regressive events in neurogenesis. Science, 225, 1258–1265.

    Article  PubMed  CAS  Google Scholar 

  • Cull-Candy, S.G., Mathie, A., Symonds, C, and Wyllie, F. (1989): Noise and single channels activated by excitatory amino acids in rat cerebellar granule neurones. J. Physiol, 400, 189–222.

    Google Scholar 

  • Cunningham, T.J. (1982): Naturally occurring neuron death and its regulation by developing neural pathways. Int. Rev. Cytol, 74, 163–186.

    Article  PubMed  CAS  Google Scholar 

  • Didier, M., Roux, P., Piechaczky, M., Verrier, B., Bockaert, J., and Pin, J.-P. (1989): Cerebellar granule cell survival and maturation induced by K+ and NMDA correlate with c-fos proto-oncogene expression. Neurosci Lett., 107, 55–62.

    Article  PubMed  CAS  Google Scholar 

  • Frandsen, A., Drejer, J., and Schousboe, A. (1989): Glutamate-induced 45Ca2+ uptake into immature cerebral cortex neurons shows a distinct pharmacological profile. J. Neurochem., 53, 1959–1962.

    Article  PubMed  CAS  Google Scholar 

  • Frandsen, A., and Schousboe, A. (1987): Time and concentration dependency of the toxicity of excitatory amino acids on cerebral neurons in primary culture. Neurochem. Int. 10, 583–591.

    Article  PubMed  CAS  Google Scholar 

  • Gallo, V., Kingsbury, A., Balâzs, R., and Jørgensen, O.S. (1987a): The role of depolarization in the survival and differentiation of cerebellar granule cells in culture. J. Neurosci, 7, 2203–2213.

    PubMed  CAS  Google Scholar 

  • Gallo, V, Suergiu, R, Giovannini, C, and Levi, G. (1987b): Glutamate receptor subtypes in cultured cerebellar neurons: modulation of glutamate and gamma-aminobutyric acid release. J. Neurochem., 49, 1801–1809.

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite, G, and Garthwaite, J. (1986a): In vitro neurotoxicity of excitatory amino acid analogues during cerebellar development. Neuroscience, 17, 755–767.

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite, G, and Garthwaite, J. (1986b): Neurotoxicity of excitatory amino acid receptor agonists in rat cerebellar slice: dependence in calcium concentration. Neurosci. Lett., 66, 193–198.

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite, G, Yamini, B, Jr., and Garthwaite, J. (1987): Selective loss of Purkinje and granule cell responsiveness to N-methyl-D-aspartate in rat cerebellum during development. Dev. Brain Res., 36, 288–292.

    Article  CAS  Google Scholar 

  • Hamburger, V, and Oppenheimer, R.W. (1982): Naturally occurring neuronal death in vertebrates. Neurosci. Commun., 1, 39–55.

    Google Scholar 

  • Honoré, T. Davies, S.N, Drejer, J,- Fletcher, E.J, Jacobson, P, Lodge, D, and Nielsen, F.E. (1988): Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science, 241, 701–703.

    Article  PubMed  Google Scholar 

  • Ito, M. (1989): Long-term depression. Annu. Rev. Neurosci., 12, 85–105.

    Article  PubMed  CAS  Google Scholar 

  • Jørgensen, O.S. (1983): D2-protein and D3-protein as markers for synaptic turnover and concentration. J. Neur. Trans., 18, 245–255.

    Google Scholar 

  • Kingsbury, A, and Balázs, R. (1987): Effect of calcium agonists and antagonists on cerebellar granule cells. Eur. J. Pharmacol, 140, 275–283.

    Article  PubMed  CAS  Google Scholar 

  • Kingsbury, A, Gallo, V, and Balázs, R. (1988): Stimulus-coupled release of amino acids from cerebellar granule cells in culture. Brain Res., 448, 46–52.

    Article  PubMed  CAS  Google Scholar 

  • Kleinschmidt, A, Bear, M.F, and Singer, W. (1987): Blockade of “NMDA” receptors disrupts experience-dependent plasticity of kitten striate cortex. Science, 238, 355–358.

    Article  PubMed  CAS  Google Scholar 

  • Lasher, R.S, and Zagon, I.S. (1972): The effect of potassium on neuronal differentiation in cultures of dissociated newborn rat cerebellum. Brain Res., 41, 482–488.

    Article  PubMed  CAS  Google Scholar 

  • Levi-Montalcini, R. (1982): Developmental neurobiology and the natural history of nerve growth factor. Annu. Rev. Neurosci. 5, 341–361.

    Article  PubMed  CAS  Google Scholar 

  • Lincoln, J, Coopersmith, R, Harris, E.W, Cotman, C.N, and Leon, M. (1988): NMDA receptor activation and olfactory learning. Dev. Brain Res., 39, 309–312.

    Article  CAS  Google Scholar 

  • Manev, H, Costa, E, Wroblewski, J.T, and Guidotti, A. (1990): Abusive stimulation of excitatory amino acid receptors: A strategy to limit neurotoxicity. FASEB J, 4, 2789–2797.

    CAS  Google Scholar 

  • Manthorpe, M, Fagnani, R, Skaper, S.D, and Varon, S. (1986): An automated colorimetric microassay for neurotrophic factors. Dev. Brain Res., 25, 191–198.

    Article  CAS  Google Scholar 

  • Maragos, W.F, Penney, J.B, and Young, A.B. (1988): Anatomic correlation of NMDA and 3H-TCP-labeled receptors in rat brain. J. Neurosci., 8, 493–501.

    PubMed  CAS  Google Scholar 

  • Mattson, M, Dou, P, and Kater, S.B. (1988): Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons. J. Neurosci., 8, 2087–2100.

    PubMed  CAS  Google Scholar 

  • Mayer, M, and Westbrook, G.L. (1987): The physiology of excitatory amino acids in the vertebrate central nervous system. Prog. Neurobiol, 28, 197–276.

    Article  PubMed  CAS  Google Scholar 

  • Meier, E, Regan, CM, and Balázs, R. (1984): Changes in the expression of a neuronal surface protein during development of cerebellar neurons in vivo and in culture. J. Neurochem., 43, 1328–1335.

    Article  PubMed  CAS  Google Scholar 

  • Meldrum, B, and Garthwaite, J. (1990): Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol. Sci., 11, 379–387.

    Article  PubMed  CAS  Google Scholar 

  • Miller, S.G, and Kennedy, M.B. (1986): Regulation of brain type II Ca2+/calmodulin-dependent protein kinase by autophosphorylation: A Ca2+-triggered molecular switch. Cell, 44, 861–870.

    Article  PubMed  CAS  Google Scholar 

  • Monaghan, D.T, Bridges, R.S, and Cotman, C.W. (1989): The excitatory amino acid receptors: Their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu. Rev. Pharmacol. Toxicol, 29, 365–402.

    Article  PubMed  CAS  Google Scholar 

  • Moran, J, and Patel, A.J. (1990): Stimulation of AT-methyl-D-aspartate receptor promotes the biochemical differentiation of cerebellar granule neurons and not astrocytes. Brain Res. 486, 215–225.

    Google Scholar 

  • Morgan, J.J, and Curran, T. (1991): Stimulus-transmission coupling in the nervous system: Involvement of inducible proto-oncogenes fos and jun. Annu. Rev. Neurosci. 14, 421–452.

    Article  PubMed  CAS  Google Scholar 

  • Morris, R.G.M, Anderson, E, Lynch, G.S, and Baudry, M. (1986): Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature, 319, 774–776.

    Article  PubMed  CAS  Google Scholar 

  • Novelli, A, Nicoletti, F, Wroblewski, J.T, Alho, H, Costa, E, and Guidotti, A. (1987): Excitatory amino. acid receptors coupled with guanylate cyclase in primary cultures of cerebellar granule cells. J. Neurosci, 7, 40–47.

    PubMed  CAS  Google Scholar 

  • Nybroe, O., Albrechtsen, M., Dahlin, J., Linnemann, D., Lyles, J.M., Moller, C.S., and Bock, E. (1985): Biosynthesis of the neuronal cell adhesion molecule: Characterization of polypeptide C. J. Cell Biol, 10, 1–6.

    Google Scholar 

  • Olverman, H.J., Jones, A.W., and Watkins, J.C. (1984): L-glutamate has higher affinity than other amino acids for [3H]-D-AP5 binding sites in rat brain membranes. Nature, 307, 460–462.

    Article  PubMed  CAS  Google Scholar 

  • Patel, A.J, Hunt, A., and Sanfeliu, C. (1990): Cell-type specific effects of N-methyl-D-aspartate on biochemical differentiation of subcortical neurons in culture. Int. J. Dev. Neurosci, 8, 379–389.

    Article  CAS  Google Scholar 

  • Pearce, I.A., Cambray-Deakin, M.A., and Burgoyne, R.D. (1987): Glutamate acting on NMDA receptors stimulate neurite outgrowth from cerebellar granule cells. FEBS Lett., 223, 143–147.

    Article  PubMed  CAS  Google Scholar 

  • Rakic, P., and Sidman, R.L. (1973): Organization of the cerebellar cortex secondary to deficit of granule cells in weaver mutant mice. J. Comp. Neurol, 152, 133–162.

    Article  PubMed  CAS  Google Scholar 

  • Rauschecker, J.P., and Hahn, S. (1987): Ketamine-xylazine anaesthesia blocks consolidation of ocular dominance changes in kitten visual cortex. Nature, 326, 183–185.

    Article  PubMed  CAS  Google Scholar 

  • Rothman, S.M. (1983): Synaptic activity mediates death of hypoxic neurons. Science, 30, 536–537.

    Article  Google Scholar 

  • Rothman, S.M., and Olney, J.W. (1987): Excitotoxicity and the NMDA receptor. Trends Neurosci, 10, 299–302.

    Article  CAS  Google Scholar 

  • Ruijter, J.M., and Baker, R.E. (1990): The effects of potassium-induced depolarisation, glutamate receptor antagonists and N-methyl-D-aspartate on neuronal survival in cultured neocortex explants. Int. J. Dev. Neurosci, 8, 361–370.

    Article  PubMed  CAS  Google Scholar 

  • Saitoh, T., and Schwartz, J.H. (1985): Phosphorylation-dependent subcellular translocation of Ca2+-calmodulin-dependent protein kinase produces an autonomous enzyme in Aplysia neurons. J. Cell Biol, 100, 835–842.

    Article  PubMed  CAS  Google Scholar 

  • Somogyi, P., Halasy, K., Somogyi, J., Storm-Mathisen, S., and Ottersen, O.P. (1986): Quantification of immunogold labeling reveals enrichment of glutamate in mossy and parallel fiber terminals in cat cerebellum. Neurosci, 19, 1045–1050.

    Article  CAS  Google Scholar 

  • Stone, T.W., and Burton, N.R. (1988): NMDA receptor and ligands in the vertebrate CNS. Prog. Neurobiol, 30, 333–368.

    Article  CAS  Google Scholar 

  • Székely, A.M., Barbaccia, M.L., Alho, H., and Costa, E. (1989): In primary cultures of cerebellar granule cells the activation of N-methyl-D-aspartate-sensitive glutamate receptors induces c-fos mRNA expression. Mol. Pharmacol, 35, 401–408.

    PubMed  Google Scholar 

  • Thangnipon, W., Kingsbury, A., Webb, M., and Balázs, R. (1983): Observations on rat cerebellar cells in vitro: Influence of substratum, potassium concentration and relationship between neurones and astrocytes. Dev. Brain Res., 11, 177–189.

    Article  CAS  Google Scholar 

  • Thoenen, H. (1991): The changing scene of neurotrophic factors. Trends Neurosci, 14, 165–170.

    Article  PubMed  CAS  Google Scholar 

  • Trenker, E, Smith, D., and Segil, N. (1984): Is cerebellar granule cell migration regulated by an internal clock? J. Neurosci, 4, 2850–2855.

    Google Scholar 

  • Varon, S., Pettman, B., and Manthorpe, M. (1988): Humoral and surface-anchored factors in development and repair of the nervous system. Progr. Brain Res., 78, 465–487.

    Article  Google Scholar 

  • Watkins, J.C, and Evans, R.H. (1981): Excitatory amino acid transmitters. Annu. Rev. Pharmacol Toxicol. 21, 165–204.

    Article  PubMed  CAS  Google Scholar 

  • Wong, E.H.F., Kemp, J.A., Priestley, T, Knight, A.R., Woodruff, G.N., and Iversen, L.L. (1986): The anti-convulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc. Natl Acad. Sci. USA, 83, 7104–7108.

    Article  PubMed  CAS  Google Scholar 

  • Wong, E.H.F., Knight, A.R., and Woodruff, G.N. (1988): [3H]MK-801 labels a site on the N-methyl-D-aspartate receptor channel complex in rat brain membranes. J. Neurochem., 50, 274–281.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Robert Balâzs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicola Hack
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ole S. Jørgensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology/Biophysics, New York University Medical Center, 550 First Avenue, 10016, New York, NY, USA

    Rodolfo Llinás

  2. INSERM U-106, Hôpital de la Salpêtrière, 47 Boulevard de l’Hôpital, 75013, Paris, France

    Constantino Sotelo M.D., Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Springer-Verlag New York, Inc.

About this chapter

Cite this chapter

Balâzs, R., Hack, N., Jørgensen, O.S. (1992). Cerebellar Granule Cells and the Neurobiology of Excitatory Amino Acids. In: Llinás, R., Sotelo, C. (eds) The Cerebellum Revisited. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2840-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-2840-0_3

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7691-3

  • Online ISBN: 978-1-4612-2840-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation