Hippocampal Plasticity and Excitatory Neurotransmitters
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.
KeywordsEntorhinal Cortex Phosphonic Acid Excitatory Neurotransmitter Acidic Amino Acid Perforant Path
Unable to display preview. Download preview PDF.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Lanthorn, T. L., and Cotman, C. W., 1981, Baclofen selectively inhibits excitatory synaptic transmission in the hippocampus. Brain Res., in press.Google Scholar
- Lanthorn, T. H. et al., The effects of L-2-amino-4-phosphonobutyrate on synaptic plasticity in the perforant path, in preparation.Google Scholar
- 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
- 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
- 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