Chunk #35 — DISCUSSION — CNIH-2/-3 selectively interact with GluA1 subunits and are required for synaptic expression of GluA1-containing AMPARs in CA1 pyramidal neurons
Previous studies, including our own, report little effect of CNIH overexpression on endogenous AMPARs. However, CNIHs clearly interact with AMPARs in heterologous cells and in neurons (Harmel et al., 2012; Shi et al., 2009; Schwenk et al., 2009; Kato et al., 2010; Gill et al., 2011; Gill et al., 2012). To test if CNIHs have an important role in neurons but are expressed at saturating levels, we performed extensive analyses using genetic deletion and knock-down of CNIHs. Indeed, we found that CNIH-2/-3 deletion causes a profound and selective reduction in AMPAR-eEPSC amplitude. This is accompanied by faster decay of mEPSCs, faster deactivation and desensitization of glutamate-evoked currents from somatic patches and compromised LTP induction. These results demonstrate a critical role for CNIHs in neuronal AMPAR regulation and are particularly fascinating given that the profound synaptic changes seen with the deletion of CNIH-2/-3 match those seen with the selective deletion of GluA1 (Lu et al., 2009). Because neurons lacking CNIH proteins look physiologically similar to neurons lacking GluA1, we hypothesized that removal of CNIH-2/-3 might have different effects in various AMPAR
