AMPA Receptor Trafficking: A Road Map for Synaptic Plasticity

Signaling cascades mediating the regulated delivery and removal of AMPARs at synapses. Left. Ca²⁺ entry upon NMDAR opening leads to CaMKII activation, which in turn inhibits a RasGAP by phosphorylation. The decrease in RasGAP activity results in the accumulation of active Ras (Ras-GTP), which triggers the p42 MAPK and phosphatidylinositol-3 kinase (PI3K) leading to AMPAR synaptic delivery (LTP). Right. NMDAR-dependent Ca²⁺ entry activates a Rap-GEF, leading to an increase in the levels of active Rap (Rap-GTP). Subsequently, Rap activates the p38 MAPK cascade leading to the removal of AMPARs from synapses (LTD).