  Trafficking of AMPA receptors in and out of synapses is crucial for synaptic
plasticity. Previous studies have focused on the role of endo/exocytosis
processes or that of lateral diffusion of extra-synaptic receptors. We have now
directly imaged AMPAR movements inside and outside synapses of live neurons
using single-molecule fluorescence microscopy. Inside individual synapses, we
found immobile and mobile receptors, which display restricted diffusion.
Extra-synaptic receptors display free diffusion. Receptors could also exchange
between these membrane compartments through lateral diffusion. Glutamate
application increased both receptor mobility inside synapses and the fraction
of mobile receptors present in a juxtasynaptic region. Block of inhibitory
transmission to favor excitatory synaptic activity induced a transient increase
in the fraction of mobile receptors and a decrease in the proportion of
juxtasynaptic receptors. Altogether, our data show that rapid exchange of
receptors between a synaptic and extra-synaptic localization occurs through
regulation of receptor diffusion inside synapses.
