The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding.

Histological evidence suggests that the estrous cycle exerts a powerful effect on CA1 neurons in mammalian hippocampus. Decades have passed since this landmark observation, yet how the estrous cycle shapes dendritic spine dynamics and hippocampal spatial coding remains a mystery. Here, we used a custom hippocampal microperiscope and two-photon calcium imaging to track CA1 pyramidal neurons in female mice over multiple cycles. Estrous cycle stage had a potent effect on spine dynamics, with heightened density during periods of greater estradiol (proestrus). These morphological changes were accompanied by greater somatodendritic coupling and increased infiltration of back-propagating action potentials into the apical dendrite. Finally, tracking CA1 response properties during navigation revealed enhanced place field stability during proestrus, evident at the single-cell and population level. These results establish the estrous cycle as a driver of large-scale structural and functional plasticity in hippocampal circuits essential for learning and memory.