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. Author manuscript; available in PMC: 2016 Aug 1.
Published in final edited form as: Horm Behav. 2015 May 8;74:4–18. doi: 10.1016/j.yhbeh.2015.05.001

Figure 2.

Figure 2

Schematic illustration of the non-classical mechanisms required for E2 and ERs to enhance hippocampal memory consolidation. Phosphorylation of the p42 isoform of ERK is necessary for E2 to enhance object recognition memory consolidation. This phosphorylation is triggered by numerous upstream events including interactions between mGluR1a and the canonical ERs (ERα and ERβ), and activation of NMDA receptors, protein kinase A (PKA), and phosphatidylinositol-3-kinase (PI3K). E2-induced phosphorylation of ERK, PI3K, and Akt elicits mTOR signaling, promoting local protein synthesis. E2-activated ERK also transduces into the nucleus to phosphorylate the transcription factor CREB. Activation of ERK is also necessary for E2 to increase histone H3 acetylation; E2 increases H3 acetylation at the pII and pIV promoters of the Bdnf gene. DNA methylation is also necessary for E2 to enhance memory consolidation, although the specific genes methylated are unknown. Finally, GPER enhances memory consolidation by activating JNK, which facilitates gene expression via transcription factors such as ATF2.