Mean (a) latencies, (b) distances, and (c) swim speeds to reach the hidden escape platform across 3 days of training for wild-type (WT) (filled boxes), ER-αKO treated with EF1α-ERα (filled circles), untreated ER-αKO (open circles), and ER-αKO treated with EF1α-GFP (gray circles). WT and ER-αKO mice treated with EF1α-ERα showed reduced latencies to escape compared with untreated ER-αKO mice and ER-αKO mice treated with EF1α-GFP. A similar pattern was observed for escape distances. (d) Discrimination index for WT (striped bar), ER-αKO treated with EF1α-ERα (filled bar), untreated ER-αKO (open bar), and ER-αKO treated with EF1α-GFP (gray bar) calculated from probe trials delivered at the end of training each day during 3 days of spatial discrimination training. (e) Number of platform crossings during each probe trial. Asterisks in d indicate that the discrimination index was significantly (P < 0.05) different from that expected by chance (discrimination index score = 0). Pound signs indicate significant differences relative to the untreated ER-αKO mice. Dagger indicates a significant difference relative to the ER-αKO mice treated with EF1α-GFP. ERα, estrogen receptor-α.