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Trafficking of glutamate receptors into and out of synapses is criticallyinvolved in the plasticity of excitatory synaptic transmission. Endocytosis andexocytosis of receptors have initially been thought to account alone for thistrafficking. However, membrane proteins also traffic through surface lateraldiffusion in the plasma membrane. We describe developments inelectrophysiological and optical approaches that have allowed for the real timemeasurement of glutamate receptor surface trafficking in live neurons. Theseinclude (i) specific imaging of surface receptors using a pH sensitivefluorescent protein, (ii) design of a photoactivable drug to inactivate locallysurface receptors and monitor electrophysiologically their recovery, and(iii)application of single molecule fluorescence microscopy to directly trackthe movement of individual surface receptors with nanometer resolution insideand outside synapses. Altogether, these approaches have demonstrated thatglutamate receptors diffuse at high rates in the neuronal membrane and suggesta key role for surface diffusion in the regulation of receptor numbers atsynapses.

Multiple Routes for Glutamate Receptor Trafficking: Surface Diffusion and Membrane Traffic Cooperate to Bring Receptors to Synapses