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. 2015 Dec 10;112(52):16018–16023. doi: 10.1073/pnas.1522150112

Fig. 1.

Fig. 1.

Intrahippocampal 17β-estradiol and ERα agonist PPT (but not ERβ agonist DPN) rapidly improve general learning. (A) Learning paradigm timeline. “H” indicates habituation. (B) Behavioral paradigms, each performed with experimentally naïve mice. (C–E) Percent investigation (PI) scores of mice during object placement (Top), object recognition (Middle), or social recognition (Bottom) learning paradigms. Black bars are PI at habituation (average of H1 and H2), white/colored bars the PI at test and contain group numbers, mean ± SEM. (C) Object placement and recognition: Microinfusion of 50 nM 17β-estradiol into the hippocampus improves object placement and object recognition learning within 40 min of administration (F3, 38 = 3.14, P < 0.05 and F3, 42 = 9.56, P < 0.001, post hoc q = 3.87, df = 18, P < 0.05 and q = 7.13, df = 22, P < 0.001, respectively). Groups treated with 50 nM of 17β-estradiol also demonstrate recognition of the displaced or novel object during test (PI at test is significantly higher than habituation; t = −2.55, df = 10, P < 0.05 and t = −8.28, df = 11, P < 0.05). Social recognition: Mice receiving 50 nM of 17β-estradiol discriminate the novel individual during the social recognition task (t = 3.38, df = 11, P < 0.01). (D) Object placement: Mice receiving 100 nM and 150 nM of ERα agonist PPT distinguish the displaced object (t = 5.79, df = 12, P < 0.001 and t = 3.30, df = 10, P < 0.01). Object recognition: Administering 50 nM, 100 nM, or 150 nM PPT result in successful discrimination of the novel object (50 nM, t = 3.88, df = 7, P < 0.01; 100 nM, t = 4.16, df = 11, P < 0.01; 150 nM, t = 2.90, df = 9, P < 0.05). Social recognition: 100 nM of PPT improves social recognition learning (F3, 40 = 3.13, P < 0.05, post hoc q = 3.92, df = 22, P < 0.05). Groups administered 100 nM and 150 nM PPT demonstrate discrimination of the novel individual at test (t = 5.18, df = 10, P < 0.001 and t = 4.39, df = 10, P < 0.01). (E) Object placement: 100 nM of DPN significantly improves object placement learning (F3, 38 = 4.01, P < 0.05, post hoc q = 3.66, df = 21, P < 0.05). This group also distinguishes the displaced object at test (t = 2.67, df = 9, P < 0.05). Object and social recognition: DPN does not improve object or social recognition learning. *P < 0.05, **P < 0.01, ***P < 0.001.