Biophysical mechanisms regulating AMPA receptor accumulation at synapses

Abstract

Controlling the number of AMPA receptors at synapses is fundamental for fast synaptic transmission as well as for long term adaptations in synaptic strength. In this review, we examine the biophysical mechanisms implicated in regulating AMPAR levels at the cell surface and at synapses. We first describe the structure and function of AMPARs, as well as their interactions with various proteins regulating their traffic and function. Second we review the vesicular trafficking mechanism involving exocytosis and endocytosis, by which AMPARs reach the cell surface and are internalized, respectively. Third, we examine the properties of lateral diffusion of AMPARs and their trapping at post-synaptic densities. Finally, we discuss how these two parallel mechanisms are integrated in time and space to control changes in synaptic AMPAR levels in response to plasticity protocols. This review highlights the important role of the extra-synaptic AMPAR pool, which makes an obligatory link between vesicular trafficking and trapping or release at synapses.