Mechanisms Underlying the Rapid Facilitation of Short-Term Social Recognition Memory by Estrogens in Female Mice
This dissertation explores some of the mechanisms underlying the rapid facilitating effects of estrogens on short-term social recognition memory in female mice. It has recently been shown that estrogens and estrogen receptor agonists can rapidly facilitate short-term social recognition memory within 40 minutes of systemic or intra-hippocampal administration. However, the mechanisms driving this facilitation are not yet known. Therefore, we explored whether 1) the extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3K) cell signalling pathways and/or 2) actin polymerization or protein synthesis in the dorsal hippocampus are necessary to the rapid facilitating effects of estrogens or short-term social recognition memory in ovariectomized female mice. Furthermore, in order to explore the involvement of estrogens in other regions in the “social brain”, we investigated whether 3) estrogens or estrogen receptor agonists in the medial nucleus of the amygdala (MeA) could rapidly facilitate short-term social recognition memory. We found that 1) inhibition of either the ERK or PI3K pathway blocks estrogen-facilitated short-term social recognition memory. Estrogen receptor (ER) alpha requires both the ERK and PI3K pathways, whereas the G protein-coupled estrogen receptor 1 (GPER1) requires only the PI3K pathway, to facilitate short-term social recognition memory. Both 2) actin polymerization and protein synthesis, but not gene transcription, are required for rapid estrogen-facilitated short-term social recognition memory. Finally, 3) estrogens in the MeA can facilitate short-term social recognition memory and this appears to be driven by ERalpha, ERbeta, and the GPER1. Together, these data suggest that complex and concurrent intracellular processes drive the rapid effects of estrogens on short-term social recognition memory in the dorsal hippocampus and that regions other than the dorsal hippocampus play a role in the rapid effects of estrogens on social cognition.