Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP

Abstract

Association of PKA with the AMPA receptor GluR1 subunit via the A kinase anchor protein AKAP150 is crucial for GluR1 phosphorylation. Mutating the AKAP150 gene to specifically prevent PKA binding reduced PKA within postsynaptic densities (>70%). It abolished hippocampal LTP in 7–12 but not 4‐week‐old mice. Inhibitors of PKA and of GluR2‐lacking AMPA receptors blocked single tetanus LTP in hippocampal slices of 8 but not 4‐week‐old WT mice. Inhibitors of GluR2‐lacking AMPA receptors also prevented LTP in 2 but not 3‐week‐old mice. Other studies demonstrate that GluR1 homomeric AMPA receptors are the main GluR2‐lacking AMPA receptors in adult hippocampus and require PKA for their functional postsynaptic expression during potentiation. AKAP150‐anchored PKA might thus critically contribute to LTP in adult hippocampus in part by phosphorylating GluR1 to foster postsynaptic accumulation of homomeric GluR1 AMPA receptors during initial LTP in 8‐week‐old mice.