Fig. 7
From: Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse
Working model for the delayed expression of activity-dependent gating switch in NMDARs and AMPARs. During Induction Phase, theta burst stimulation increases intracellular Ca2+ concentration ([Ca2+]i) via coincident activation of NMDARs and mGluR1/5 at the developing calyx of Held synapse. The rise in [Ca2+]I,causes translation activation of immediate early genes, Homer1a and Arc/Arc3.1. Homer1a can lead to a rapid internalization of extra/peri-synaptic NMDARs (Expression Phase I), whilst Arc/Arc3.1 proteins are phosphorylated by CaMKII to mediate internalization of GluA1 at a slower time scale (Expression Phase II). During Expression Phase I, protein synthesis builds up a new intracellular pool of GluA4 proteins that are primed by PKC-dependent phosphorylation. This new pool can be subsequently recruited to take place of synaptic slots vacated by GluA1 channels in Expression Phase II