The Rapid Effects of the G-protein Coupled Estrogen Receptor in Various Brain Regions on Learning and Memory in Female Mice
This thesis investigates the role of the G-protein coupled estrogen receptor (GPER) in learning and memory in female mice. It has recently been shown that estrogens can affect learning and memory on a rapid time scale through the classic estrogen receptors, α and β. Very little is known about the rapid effects of the GPER on learning and memory, so we investigated the effects of GPER activation on social recognition, object recognition, and object placement learning within 40 minutes of drug administration. We found that systemic activation of the GPER, with the agonist G-1, improved all three learning and memory paradigms in female mice. To determine where in the brain these effects might be mediated, we examined the effects of systemic administration of G-1 on dendritic spines in the CA1 region of the hippocampus. We found that the GPER is involved in increasing dendritic spine in the hippocampus, a process thought to be involved in learning and memory. Therefore, we next investigated the role of the GPER, specifically in the dorsal hippocampus, in the rapid estrogenic facilitation of learning and memory. Intrahippocampal activation of the GPER rapidly improved social recognition and object recognition, but not object placement in ovariectomized female mice within 40 minutes. Additionally, we found that intrahippocampal administration of G-1 rapidly improved social recognition and object recognition when tested in a Y-apparatus, instead of the home cage, where there were minimal spatial cures present. As the medial amygdala is also known to be involved in social recognition, we examined the role of the GPER in the medial amygdala on social recognition in female mice. We found that intra-medial amygdala activation of the GPER rapidly improved social recognition. Therefore, the GPER is involved in the rapid estrogenic facilitation of learning and memory in female mice. Specifically, the GPER in the hippocampus is involved in the facilitation of social recognition and object recognition, and not necessarily involved in the processing of spatial information. Additionally, the GPER in the medial amygdala appears to also be involved in the estrogenic facilitation of social recognition.