Maintenance of late-phase LTP is accompanied by PKA-dependent increase in AMPA receptor synthesis

Nature. 1998 Aug 13;394(6694):680-3. doi: 10.1038/29305.


Long-term potentiation (LTP) is a form of synaptic plasticity that has been extensively studied as a putative mechanism underlying learning and memory. A late phase of LTP occurring 3-5 hours after stimulation and depending on transcription, protein synthesis and cyclic-AMP-dependent protein kinase (protein kinase A, or PKA) has been described, but it is not known whether transcription of presynaptic and/or postsynaptic genes is required to support late-phase LTP. Here we show that late-phase LTP can be obtained in rat hippocampal CA1 mini-slices in which the cell bodies of presynaptic Schaffer collateral/commissural fibres are removed. Thus, transcription of presynaptic genes is not necessary to support maintenance of late-phase LTP. The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor is the predominant mediator of the ionotropic response to synaptically released glutamate in the hippocampus and it has been implicated in LTP maintenance. We find that synthesis of AMPA receptor subunits is increased three hours after LTP induction: this effect on the synthesis of the AMPA receptor is blocked by inhibitors of PKA and of transcription. Our results support the idea of a postsynaptic mechanism maintaining late-phase LTP, in which AMPA receptor synthesis is increased as a result of PKA-dependent gene transcription.

MeSH terms

  • Animals
  • Blotting, Western
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cysteine / metabolism
  • Enzyme Activation
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Methionine / metabolism
  • Precipitin Tests
  • Rats
  • Receptors, AMPA / biosynthesis*
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Subcellular Fractions / metabolism
  • Synaptic Transmission / physiology
  • Transcription, Genetic


  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • glutamate receptor ionotropic, AMPA 3
  • Methionine
  • Cyclic AMP-Dependent Protein Kinases
  • Cysteine
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1