Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype.
Liu, Si-Qiong June; Cull-Candy, Stuart G.
[Letter] Nature. 405(6785):454-458, May 25, 2000.

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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 1,2 or Ca2 -permeable AMPARs 3-6. This process is thought to involve alteration in the number and phosphorylation state of postsynaptic AMPARs 2. 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 7 but also are blocked by intracellular polyamines 8-11. 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.

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