Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype

Nature. 2000 May 25;405(6785):454-8. doi: 10.1038/35013064.


Activity-dependent change in the efficacy of transmission is a basic feature of many excitatory synapses in the central nervous system. The best understood postsynaptic modification involves a change in responsiveness of AMPAR (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor)-mediated currents following activation of NMDA (N-methyl-D-aspartate) receptors or Ca2+-permeable AMPARs. This process is thought to involve alteration in the number and phosphorylation state of postsynaptic AMPARs. Here we describe a new form of synaptic plasticity--a rapid and lasting change in the subunit composition and Ca2+ permeability of AMPARs at cerebellar stellate cell synapses following synaptic activity. AMPARs lacking the edited GluR2 subunit not only exhibit high Ca2+ permeability but also are blocked by intracellular polyamines. These properties have allowed us to follow directly the involvement of GluR2 subunits in synaptic transmission. Repetitive synaptic activation of Ca2+-permeable AMPARs causes a rapid reduction in Ca2+ permeability and a change in the amplitude of excitatory postsynaptic currents, owing to the incorporation of GluR2-containing AMPARs. Our experiments show that activity-induced Ca2+ influx through GluR2-lacking AMPARs controls the targeting of GluR2-containing AMPARs, implying the presence of a self-regulating mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepines / pharmacology
  • Calcium / physiology
  • Cell Membrane Permeability
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials
  • Glutamic Acid / pharmacology
  • In Vitro Techniques
  • Ion Channel Gating
  • Neuronal Plasticity
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / agonists
  • Receptors, AMPA / physiology*
  • Synapses / physiology*
  • Synaptic Membranes / metabolism
  • Synaptic Membranes / physiology


  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Benzodiazepines
  • GYKI 53655
  • Glutamic Acid
  • glutamate receptor ionotropic, AMPA 2
  • Calcium