AMPA-type glutamate synaptic receptors (AMPA-Rs) mediate a wide variety of excitatory synaptic transmissions in the brain. The mechanism by which these receptors maintain a long-term synaptic efficacy are not fully understood. In the 4 May Cell Song-Hai Shi and colleagues at Cold Spring Harbor Laboratory, New York show that AMPA-Rs in hippocampus use a number of delivery mechanisms to stabilize long-term changes in synaptic efficacy.

Most hippocamic AMPA-Rs are hetero-oligomers composed of GluR1/GluR2 or GluR2/GluR3 subunits. Using an in vitro electrophysiological recording system for cell preparations, Shi et al showed that only GluR1/GluR2 receptors are added to synapses during synaptic activity; requiring interactions between GluR1 and group I PDZ domain proteins. In contrast, GluR2/GluR3 receptors replace existing synaptic receptors continuously and do not require activity. This occurs at synapses that already have AMPA-Rs and involves interactions by GluR2 with NSF and group II PDZ domain proteins (Cell 2001,...

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