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Long-Term Inhibition of Synaptic Transmission and Macromolecular Synthesis Following Anoxia in the Rat Hippocampal Slice: Interaction between Ca2+ and NMDA Receptors

  • Peter Lipton
  • Kate Raley
  • Doub Lobner
Part of the Advances in Behavioral Biology book series (ABBI, volume 35)

Summary

The rat hippocampal slice is becoming a quite widely used system for studying anoxic damage in brain tissue. We have been using it to study the long-term effects of short anoxic exposures on specific functions, in particular synaptic transmission and synthesis of protein and RNA. The first two of these functions are strongly inhibited for many hours after short exposures to anoxia or “ischemia”. RNA synthesis is less readily damaged; it only becomes permanently damaged following 20 minutes of anoxia without glucose.

Much of the chapter explores the mechanism of the long-term damage to synaptic transmission. Data strongly suggest that the early fall in ATP is the primary trigger for damage. There is a significant uptake of calcium into the tissue during anoxia, due to inhibition of Ca2+-extrusion across the plasmalemma and there is quite strong evidence that this increase is a major subsequent event in the damage sequence. Binding of glutamate to NMDA-type receptors is also important for the development of damage and evidence is presented which argues that this binding does not act to increase Ca2+ entry from the extracellular space. It is suggested that it acts by leading to the release of calcium from intracellular stores.

The relationship of the in vitro damage to ischemic damage in situ is discussed and it is concluded that there are important similarities.

Keywords

NMDA Receptor Cerebral Ischemia Synaptic Transmission Hippocampal Slice Extracellular Calcium 
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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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Peter Lipton
    • 1
  • Kate Raley
    • 1
  • Doub Lobner
    • 1
  1. 1.Department of PhysiologyUniversity of WisconsinMadisonUSA

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