AMPA Receptor Trafficking for Postsynaptic Potentiation

Long-term potentiation (LTP) of excitatory synaptic strength, which has long been considered a synaptic correlate for learning and memory, requires a fast recruitment of additional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs) to the postsynaptic sites. As cell biological concepts have been applied to the field and genetic manipulation and microscopic imaging technologies have been advanced, visualization of the trafficking of AMPARs to synapses for LTP has been investigated intensively over the last decade. Recycling endosomes have been reported as intracellular storage organelles to supply AMPARs for LTP through the endocytic recycling pathway. In addition, exocytic domains in the spine plasma membrane, where AMPARs are inserted from the intracellular compartment, and nanodomains, where diffusing AMPARs are trapped and immobilized inside synapses for LTP, have been described. Furthermore, cell surface lateral diffusion of AMPARs from extrasynaptic to synaptic sites has been reported as a key step for AMPAR location to the synaptic sites for LTP. This review article will discuss recent findings and views on the reservoir(s) of AMPARs and their trafficking for LTP expression by focusing on the exocytosis and lateral diffusion of AMPARs, and provide some future directions that need to be addressed in the field of LTP.