amplitude by ~20% (Figure 2G), similar to that observed with CNIH-2 elimination (Figure 2I), while mEPSC decay was faster than elimination of CNIH-2 alone (Figures 2H and J). In figures 2E,F,I and J our CNIH KO results are summarized and compared to previous results obtained by the conditional KO of GluA1 (Lu et al., 2009). Strikingly, the effects of CNIH-2/-3 elimination on the AMPAR-eEPSC, mEPSC amplitude, and kinetics are indistinguishable from the effects of deleting GluA1. Interestingly, previous studies on the germline GluA1 KO mouse (Andrasfalvy et al., 2003; Zamanillo et al., 1999) did not report a speeding of mEPSCs. We repeated these experiments, however, and observed the same speeding as we found in the conditional GluA1 KO neurons (Figure S3). We have no clear explanation for the difference, although Andrasfalvy et al. (Andrasfalvy et al., 2003) did report faster deactivation in outside out patches from the germline KO mouse. Long-term potentiation (LTP), which is widely held as the cellular basis for learning and memory, is also found to be severely reduced in hippocampal neurons from GluA1 KO mice (Zamanillo et al., 1999). We, therefore, examined LTP in neurons lacking CNIH-2/-3. If GluA1-containing AMPARs are removed from synapses in the
