Polyamine-dependent facilitation of postsynaptic AMPA receptors counteracts paired-pulse depression

Nature. 1999 Oct 7;401(6753):594-8. doi: 10.1038/44151.


At many glutamatergic synapses in the brain, calcium-permeable alpha - amino - 3 - hydro - 5 - methyl - 4 - isoxazolepropionate receptor (AMPAR) channels mediate fast excitatory transmission. These channels are blocked by endogenous intracellular polyamines, which are found in virtually every type of cell. In excised patches, use-dependent relief of polyamine block enhances glutamate-evoked currents through recombinant and native calcium-permeable, polyamine-sensitive AMPAR channels. The contribution of polyamine unblock to synaptic currents during high-frequency stimulation may be to facilitate currents and maintain current amplitudes in the face of a slow recovery from desensitization or presynaptic depression. Here we show, on pairs and triples of synaptically connected neurons in slices, that this mechanism contributes to short-term plasticity in local circuits formed by presynaptic pyramidal neurons and postsynaptic multipolar interneurons in layer 2/3 of rat neocortex. Activity-dependent relief from polyamine block of postsynaptic calcium-permeable AMPARs in the interneurons either reduces the rate of paired-pulse depression in a frequency-dependent manner or, at a given stimulation frequency, induces facilitation of a synaptic response that would otherwise depress. This mechanism for the enhancement of synaptic gain appears to be entirely postsynaptic.

MeSH terms

  • Animals
  • Excitatory Postsynaptic Potentials
  • In Vitro Techniques
  • Interneurons / physiology
  • Neocortex / physiology
  • Neuronal Plasticity
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / physiology*
  • Spermine / physiology*
  • Synaptic Transmission / physiology*
  • Temperature


  • Receptors, AMPA
  • Spermine