Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons

AMPA-type glutamate receptors (AMPA-Rs) mediate a majority of excitatory sy naptic transmission in the brain. In hippocampus, most AMPA-Rs are heterool igomers composed of GluR1/GluR2 or GluR2/GluR3 subunits. Here we show that these AMPA-R forms display different synaptic delivery mechanisms. GluR1/ G luR2 receptors are added to synapses during plasticity; this requires inter actions between GluR1 and group I PDZ domain proteins. In contrast, GluR2/G luR3 receptors replace existing synaptic receptors continuously; this occur s only at synapses that already have AMPA-Rs and requires interactions by G luR2 with NSF and group I! PDZ domain proteins. The combination of regulate d addition and continuous replacement of synaptic receptors can stabilize l ong-term changes in synaptic efficacy and may serve as a general model for how surface receptor number is established and maintained.