The rapid effects of Hippocampal Estrogen receptors on social recognition learning in female mice (#270)
Estrogens rapidly affect a number of learning and memory tasks, including social recognition learning (Phan et al., 2011, 2012). Within 40 minutes of systemic administration, 17β-estradiol, the estrogen receptor (ER) α agonist, PPT, and the recently discovered G-protein coupled estrogen receptor (GPER) agonist, G-1, each improved social recognition learning in ovariectomized female mice within the test mouse home cage. However, the ER β agonist, DPN, impaired social recognition. Within this timeframe, systemic administration of 17β-estradiol and PPT also increased dendritic spine density in the CA1 of the hippocampus. Thus, the following studies investigated the role of the different ERs in the CA1 region of the hippocampus on social recognition in ovariectomized female mice. The paradigm consists of two 5min habituations and one 5min test (5min intertest intervals) where two stimulus mice are presented to the test mouse. Within the test mouse home cage, intrahippocampal administration of 17β-estradiol (50nM), PPT (100 and 150nM), and G-1 (200 and 400nM) improved social recognition while DPN had no effect. Co-infusion of subeffective doses of G-1 (100nm) and PPT (50nM) improved social recognition. The home cage provides a number of spatial and contextual cues the mouse can use to complete the task. Hence, we used a Y-maze, designed to eliminate most of these cues. Intrahippocampal administration of 17β-estradiol had no effect on social recognition in the Y-maze but systemic administration improved it. The effects of GPER in the hippocampus on social recognition in the Y-maze are currently underway. These studies indicate that estrogens, through the additive action of ER α and GPER in the hippocampus, enhance the spatial aspects of social recognition learning in female mice, while it appears that estrogens acting in a brain region other than the hippocampus are involved in enhancing social recognition learning in the absence of spatial cues.