Estrogenic regulation of memory consolidation: A look beyond the hippocampus, ovaries, and females

The potent estrogen 17β-estradiol (E2) has long been known to regulate the hippocampus and hippocampal-dependent memories in females, and research from the past decade has begun to shed light on the molecular mechanisms through which E2 mediates memory formation in females. Although E2 can also regulate hippocampal function in males, relatively little is known about how E2 influences memory formation in males, or whether sex differences in underlying mechanisms exist. This review, based on a talk given in April 2017 at the American University symposium entitled, “Sex Differences: From Neuroscience to the Clinic and Beyond”, first provides an overview of the molecular mechanisms in the dorsal hippocampus through which E2 enhances memory consolidation in ovariectomized female mice. Next, newer research is described demonstrating key roles for the prefrontal cortex and de novo hippocampal E2 synthesis to the memory-enhancing effects of E2 in females. The review then discusses the effects of de novo and exogenous E2 on hippocampal memory consolidation in both sexes, and putative sex differences in the underlying molecular mechanisms through which E2 enhances memory formation. The review concludes by discussing the importance and implications of sex differences in the molecular mechanisms underlying E2-induced memory consolidation for human health. •Estradiol (E2) rapidly enhances hippocampal memory consolidation in both sexes.•Many underlying molecular mechanisms are known in females, but not males.•Putative sex differences in these molecular mechanisms are described.•Role for the prefrontal cortex in effects of hippocampal E2 infusion is discussed.•Involvement of de novo hippocampal E2 synthesis in both sexes is considered.