Figure 2.

Our current working model of the molecular mechanisms mediating the rapid effects of E₂ on memory consolidation. ERα and ERβ could influence memory by binding to coregulators, including HATs, and stimulating estrogen response element (ERE)-mediated gene transcription. Alternatively, E₂ may rapidly enhance memory consolidation by triggering interactions between ERs and metabotropic glutamate receptors (mGluRs), NMDA receptor activation, and/or membrane ER activation, all of which can activate ERK and mammalian target of rapamycin (mTOR) signaling in dorsal hippocampal neurons. Activation of ERK then leads to histone H3 acetylation, and potentially the methylation of memory repressor genes like Hdac2, Hdac3, or reelin, causing increased expression of genes that facilitate protein synthesis and memory consolidation. This model is based on my laboratory's findings (32, 33, 87-90, 105), some of which are discussed in more detail in the main text.