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)


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.


Entorhinal Cortex Phosphonic Acid Excitatory Neurotransmitter Acidic Amino Acid Perforant Path 
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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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