Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype.
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.
Liu
S Q
SQ
Department of Pharmacology, University College London, UK.
Cull-Candy
S G
SG
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002463:Cell Membrane Permeability; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D001569:Benzodiazepines; C079692:GYKI 53655; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium