Intrahippocampal Infusion of G-protein Coupled Estrogen Receptor Agonist Increases CA1 Spine Density and Enhances Memory Consolidation

Little is known about the role of G-protein-coupled estrogen receptors (GPER) in hippocampal synaptic plasticity and memory consolidation. G-1 is a GPER agonist that mimics the memory-enhancing effects of 17?-estradiol (E2), a potent estrogen. However, the mechanisms through which G-1 enhances memory remain unclear. Here, we examined the effects of dorsal hippocampal infusion of G-1 on memory consolidation and CA1 dendritic spines. In Experiment 1, ovariectomized mice received bilateral dorsal hippocampal infusion of G-1 (4 µg) or vehicle immediately after training in the object recognition and object placement tasks. Compared to vehicle, G-1 significantly increased the time spent with the novel or moved objects, indicating an enhancement of hippocampal-dependent object recognition and spatial memory. In Experiment 2, ovariectomized mice received DH infusions of vehicle or G-1, and then brain tissue was collected 40 minutes later for Golgi staining and dendritic spine analysis. Compared to vehicle, G-1 significantly increased apical dendritic spine density on pyramidal neurons in the CA1 region of the hippocampus. Further analysis showed that G-1 specifically increased the number of mushroom spines, but not thin or stubby spines. These findings suggest that G-1 may enhance hippocampal-dependent memory by increasing mature apical dendritic spines in CA1