Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice

The potent estrogen 17 beta-Estradiol (E-2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E-2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E-2 on memory are generally attributed to ovarian-synthesized E-2. However, E-2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E-2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E-2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E-2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E-2 in the dorsal hippocampus observed 30 min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E-2 synthesis. Finally, aromatase inhibition did not prevent exogenous E-2 from enhancing hippocampal memory consolidation, indicating that hippocampal E-2 synthesis is not necessary for exogenous E-2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally synthesized E-2 is necessary for hippocampus-dependent memory consolidation in rodents. (C) 2016 Elsevier Inc. All rights reserved.