17β-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms

Abstract

Although 17β-estradiol has long been known to regulate memory function, the molecular mechanisms underlying estrogenic memory modulation remain largely unknown. Here, we examined whether the putative membrane estrogen receptor GPER acts like the classical estrogen receptors, ERα and ERβ, to facilitate hippocampal memory in female mice. Although GPER activation did enhance object recognition and spatial memory, it did so by activating different cell-signaling mechanisms from ERα, ERβ, or 17β-estradiol. These data indicate that 17β-estradiol and GPER independently regulate hippocampal memory, and suggest that hippocampal GPER may not function as an estrogen receptor in the dorsal hippocampus. These findings are significant because they provide novel insights about the molecular mechanisms through which 17β-estradiol modulates hippocampal memory.