CNIH-3 is also expressed in hippocampus, although at a lower level than CNIH-2 (Lein et al., 2007). We therefore analyzed Cnih3fl/fl mice (Figures S1B–C). We found that deleting CNIH-3 had no effect on AMPAR- or NMDAR-eEPSCs (Figures 2A–B), suggesting that either CNIH-3 is not expressed in these neurons or that an excess of CNIH-2 compensates for the loss of CNIH-3. To distinguish between these alternatives, we generated Cnih2/3fl/fl mice. Deletion of both CNIH-2 and -3 resulted in a profound and selective reduction in the AMPAR-eEPSC, significantly greater than that seen with CNIH-2 deletion alone (Figures 2C–F). These results suggest that CNIH-2 can compensate for the lack of CNIH-3, that CNIH-2 is the dominant of the two isoforms and that CNIH-2 and -3 are both essential for synaptic AMPAR expression in the hippocampus. Deletion of CNIH-2 and -3 also reduced mEPSC 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
