Hippocampal Plasticity and Excitatory Neurotransmitters

  • Carl W. Cotman
  • Graham E. Fagg
  • Thomas H. Lanthorn
Part of the Advances in Behavioral Biology book series (ABBI, volume 26)

Summary

The identification of excitatory transmitters used at specific pathways in the CNS is a major, but as yet largely unsolved problem which is of critical importance for analyzing the mechanisms of learning and memory. The hippocampus appears to be involved in several aspects of learning and is an excellent model system for the study of these processes. Much evidence favors the idea that glutamate is the transmitter of the perforant path, the major cortical input to the hippocampus. Thus, glutamate release in the dentate gyrus is Ca 2+-dependent and stimulated by depolarization; removal of the perforant path reduces this release as well as the high affinity uptake of glutamate. The glutamate analogue, L-2amino-4-phosphonobutyric acid, selectively blocks synaptic transmission at the lateral but not medial perforant path. The dose required to reduce transmission by 50% is about 3 u m, making this drug the most potent antagonist of excitatory amino acid transmission in the brain. The action is selective to the L-isomer and shorter or longer chain derivatives are less effective. The transmitters of the Schaffer collateral/commissural input to CA1 neurons appear to be glutamate and aspartate based on release and uptake data. An effective antagonist for this pathway has not been found at the present time. The transmitter of the mossy fiber system is unknown, although evidence exists which suggests the involvement of a kainic acid-like molecule. Plasticity studies using L-APB show that paired pulse potentiation in the lateral perforant path is enhanced in the presence of the drug, probably due to interactions with presynaptic release mechanisms.

Keywords

Entorhinal Cortex Phosphonic Acid Excitatory Neurotransmitter Acidic Amino Acid Perforant Path 
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.

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References

  1. Biscoe, T. J., and Straughan, D. W., 1966, Micro-electrophoretic studies on neurones in the cat hippocampus, J. Physiol. (Lond.), 183: 341–359.Google Scholar
  2. Biziere, K., Thompson, H., and Coyle, J. T., 1980, Chlracterization of specific, high affinity binding sites for L-[H]glutamic acid in rat brain membranes, Brain Res. 183: 421–423.PubMedCrossRefGoogle Scholar
  3. Cotman, C. W., 1980, Acidic amino acids as excitatory transmitters, In: Regulatory Mechanisms of Synaptic Transmission, ( R. Tapia and C. W. Cotman, Eds.), Plenum Press, New York, pp. 43–57.Google Scholar
  4. Cotman, C. W., Foster, A. C., and Lanthorn, T. L., 1981, An overview of glutamate as a neurotransmitter. In: Glutamate as a Neurotransmitter, ( G. DiChiara and G. L. Gessa, Eds.), Raven Press, New York, pp. 1–27.Google Scholar
  5. Cotman, C. W., and Nadler, J. V., 1981, Glutamate and Aspartate as hippocampal transmitters: biochemical and pharmacological evidence, In: Glutamate: Transmitter in the Central Nervous System, ( P. J. Roberts, J. Storm-Mathisen and G. A. R. Johnston, Eds.), John Wiley & Sons, New York, pp. 117–154.Google Scholar
  6. Crawford, I. L., and Conner, J. D., 1973, Localization and release of glutamic acid in relation to the hippocampal mossy fibre pathway, Nature, 244: 442–443.PubMedCrossRefGoogle Scholar
  7. Davies, J., Francis, A. A., Jones, A. W., and Watkins, J. C., 1981, 2-amino-5-phosphono valerate (2APV), a potent and selectve antagonist of amino acid-induced and synaptic excitation, Neurosci. Lett.21: 77–81.Google Scholar
  8. Evans, R. H., Jones, A. W., and Watkins, J. C., 1981, Depressant action of the L-glutamate analogue (+)2-amino-4-phosphonobutyrate, Br. J. Pharmacol., in press.Google Scholar
  9. Fagg, G. E., and Lane, J. D., 1979, The uptake and release of putative amino acid neurotransmitters, Neuroscience 4: 1015–1036.PubMedCrossRefGoogle Scholar
  10. Fagg, G. E., Foster, A. C., Mena, E. E., Koerner, J. F., and Cotman, C. W., 1981, Calcium ions and the pharmacology of acidic amino acid receptor sites, Trans. Am. Soc. Neurochem. 12: 121.Google Scholar
  11. Foster, A. C., and Roberts, P. J., 1978, High affinity L-[H]glutamate binding to postsynaptic receptor sites in rat cerebellar membranes, J. Neurochem.31: 1467–1477.PubMedCrossRefGoogle Scholar
  12. Foster, A. C., Mena, E. E., Monaghan, D. T., and Cotman, C. W., 1981a, Synaptic localization of kainic acid binding sites, Nature 289: 73–35.PubMedCrossRefGoogle Scholar
  13. Foster, A. C., Mena, E. E., Fagg, G. E., and Cotman, C. W., 1981b, Glutamate and aspartate binding sites are enriched in synaptic junctions isolated from rat brain, J. Neurosci.1: 620–625.PubMedGoogle Scholar
  14. Hamberger, A., Chiang, G., Nylen, E. S., Scheff, S. W., and Cotman, C. W., 1978, Stimulus evoked increase in the biosynthesis of the putative neurotransmitter glutamate in the hippocampus, Brain Res. 143: 549–555.PubMedCrossRefGoogle Scholar
  15. Hamberger, A. C., Chiang, G. H., Nylen, E. S., Scheff, S. W., and Cotman, C. W., 1979a, Glutamate as a CNS transmitter. I. Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate, Brain Res. 168: 513–530.PubMedCrossRefGoogle Scholar
  16. Hamberger, A. C., Chiang, G. H., Nylen, E. S., Scheff, S. W., and Cotman, C. W., 1979b, Glutamate as a CNS transmitter. II. Regulation of synthesis in the releasable pool, Brain Res. 168: 531–541.PubMedCrossRefGoogle Scholar
  17. Koerner, J. R., and Cotman, C. W., 1981, Micromolar L-2-amino-4-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex, Brain Res. 216: 192–198.PubMedCrossRefGoogle Scholar
  18. Lanthorn, T. L., and Cotman, C. W., 1981, Baclofen selectively inhibits excitatory synaptic transmission in the hippocampus. Brain Res., in press.Google Scholar
  19. Lanthorn, T. H. et al., The effects of L-2-amino-4-phosphonobutyrate on synaptic plasticity in the perforant path, in preparation.Google Scholar
  20. Nadler, J. V., Vaca, K. W., White, W. F., Lynch, G. S., and Cotman, C. W., 1976, Aspartate and glutamate as possible transmitters of excitatory hippocampal afferents, Nature 260: 538–540.PubMedCrossRefGoogle Scholar
  21. Nadler, J. V., White, W. F., Vaca, K. W., Perry, B. W., and Cotman, C. W., 1978, Biochemical correlates of transmission mediated by glutamate and asparate. J. Neurochem. 31: 147–155.PubMedCrossRefGoogle Scholar
  22. Potashner, S. J., 1978, Baclofen: effects on amino acid release, Can. J. Physiol. Pharmacol.56: 150–154.CrossRefGoogle Scholar
  23. Rubin, R. P., 1970, The role of calcium in the release of neurotransmitter substances and hormones, Pharmacol. Rev.22: 389–248.PubMedGoogle Scholar
  24. Sandoval, M. E., Horch, P., and Cotman, C. W., 1978, Evaluation of glutamate as a hippocampal neurotransmitter: glutamate uptake and release from synaptosomes, Brain Res. 142: 285–299.PubMedCrossRefGoogle Scholar
  25. Slaughter, M. M., and Miller, R. F., 1981, 2-amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. Science 211: 182–185.Google Scholar
  26. Storm-Mathisen, J., 1977a, Glutamic acid and excitatory nerve endings: reduction of glutamic acid uptake after axotomy, Brain Res. 120: 379–386.PubMedCrossRefGoogle Scholar
  27. Storm-Mathisen, J., 1977b, Localization of transmitter candidates in the brain: the hippocampal formation as a model, Prog. Neurobiol.8: 119–181.PubMedCrossRefGoogle Scholar
  28. Storm-Mathisen, J., 1978, Localization of putative transmitters in the hippocampal formation, with a note on the connections to septum and hypothalamus, In: Functions of the Septo-Hippocampal System, CIBA Foundation Symposium 58: 49–86.Google Scholar
  29. Storm-Mathisen, J., and Iversen, L. L., 1979, Uptake of [3H]glutamic acid in excitatory nerve endings: light and electron microscopic observations in the hippocampal formation of the rat, Neuroscience 4: 1237–1253.PubMedCrossRefGoogle Scholar
  30. Watkins, J. C., Davies, J., Evans, R. H., Francis, A. A. and Jones, A. W., 1981, Pharmacology of receptors for excitatory amino acids, In: Glutamate as a Neurotransmitters, (G. Di Chiara,and G. L. Gessa, Eds.), Raven Press, New York, pp. 263–273.Google Scholar
  31. Watkins, J. C. and Evans, R. H., 1981, Excitatory amino acid transmitters, Ann. Rev. Pharmacol. Toxicol.21: 165–204.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Carl W. Cotman
    • 1
  • Graham E. Fagg
    • 1
  • Thomas H. Lanthorn
    • 1
  1. 1.Department of PsychobiologyUniversity of CaliforniaIrvineUSA

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