AMPA-type receptors (AMPARs) are glutamate-gated channels whose postsynaptic activation convey the major depolarization in brain excitatory neurotransmission. Trafficking of these receptors to and from synapses is tightly regulated in neurons and underlies long-lasting forms of synaptic plasticity. For example, export of AMPARs from the endoplasmic reticulum to the Golgi is suggested to contribute to the expression of certain types of synaptic plasticity. In addition, endocytosis removes AMPARs from synapses during LTD and in response to other stimuli. Internalized AMPARs can be degraded in lysosomes or recycled back to the surface membrane . This AMPAR sorting is regulated by synaptic activity and provides the local intracellular pool of AMPARs needed for LTP expression. AMPARs also undergo constitutive trafficking that involves both exocytic delivery from intracellular compartments and fast exchange with surface extrasynaptic receptors through lateral diffusion. Still, knowledge is lacking regarding the organization and regulation of AMPARs within the postsynaptic density (PSD) and the events triggering their repositioning.
Principles of FRAP experiment with AMPARs. Left, Scheme illustrating photobleaching and recovery of a whole synapse (top, Full Bleaching) versus half of a synapse (bottom, Partial Bleaching). Before the bleach event, fluorescent AMPARs can be viewed on the synaptic surface (A, green dots, baseline). Immediately after photobleaching, AMPARs are no longer fluorescent (B, gray dots, total bleaching) and then fluorescence gradually recovers (C, green and gray dots, recovery) as unbleached AMPARs move into the bleached area. Note that, under basal conditions, full bleaching and partial bleaching result with the same recovery graph (right, blue line and dashed red line, respectively). When intrasynaptic mobility of AMPARs is increased (e.g., after glutamate application), there is a stronger increase in recovery following partial bleaching (right, solid red line).