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

Activity-dependent change in the efficacy of transmission is a basic featur e of many excitatory synapses in the central nervous system. The best under stood postsynaptic modification involves a change in responsiveness of AMPA R (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor)-medi ated currents following activation of NMDA (N-methyl-D-aspartate) receptors (1,2) or Ca2+-permeable AMPARs(3-6). This process is thought to involve alt eration in the number and phosphorylation state of postsynaptic AMPARs(2). Here we describe a new form of synaptic plasticity-a rapid and lasting chan ge in the subunit composition and Ca2+ permeability of AMPARs at cerebellar stellate cell synapses following synaptic activity. AMPARs lacking the edi ted GluR2 subunit not only exhibit high Ca2+ permeability(7) but also are b locked by intracellular polyamines(8-11). These properties have allowed us to follow directly the involvement of GluR2 subunits in synaptic transmissi on. 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 AMPAR s. Our experiments show that activity-induced Ca2+ influx through GluR2-lac king AMPARs controls the targeting of GluR2-containing AMPARs, implying the presence of a self-regulating mechanism.