Expression mechanisms underlying NMDA receptor-dependent long-term potentiation

Ann N Y Acad Sci. 1999 Apr 30:868:515-25. doi: 10.1111/j.1749-6632.1999.tb11320.x.

Abstract

Long-term potentiation (LTP) is currently the best available cellular model for learning and memory in the mammalian brain. In the CA1 region of the hippocampus, as well as in many other areas of the CNS, its induction requires a rise in postsynaptic Ca2+ via activation of NMDA receptors. What happens after the rise in postsynaptic Ca2+ is less clear. This paper summarizes experiments performed over the last decade in slice preparations that address the site of expression of LTP. While a large number of laboratories have contributed importantly to this issue, this review will rely primarily on experiments performed in the authors' laboratory. The experiments to be discussed can be broadly divided into two groups: those designed to determine if an increase in glutamate release occurs during LTP and those designed to determine if a change in postsynaptic sensitivity to glutamate occurs during LTP. Experiments in the first category include the analysis of dual-component excitatory postsynaptic currents (EPSCs), paired-pulse facilitation, saturating release probability, the use of MK-801 to measure release probability, and glial glutamate transporter currents to measure directly the synaptic release of glutamate. Experiments in the second category include analysis of miniature EPSC amplitudes, measurements of synaptic potency, the consequences of loading cells with the constitutively activated form of CaM kinase II, and the evidence that during LTP postsynaptically silent synapses become functional. We will argue that, while numerous experiments fail to support a presynaptic expression mechanism, many experiments do point to a postsynaptic expression mechanism. The decrease in synaptic failures during LTP, the only generally accepted experimental result that supports a presynaptic expression mechanism, can be explained by postsynaptically silent synapses. Future directions for research in this field include activity-dependent targeting of glutamate receptors and the functional consequences of phosphorylation of AMPA receptors.

Publication types

  • Review

MeSH terms

  • 4-Aminopyridine / pharmacology
  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Transport System X-AG
  • Animals
  • Brain / metabolism
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Dizocilpine Maleate / pharmacology
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Long-Term Potentiation / physiology*
  • Memory
  • Neuroglia
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synaptic Transmission

Substances

  • ATP-Binding Cassette Transporters
  • Amino Acid Transport System X-AG
  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Dizocilpine Maleate
  • 4-Aminopyridine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium