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

Histological evidence suggests that the estrous cycle exerts a powerful influence on CA1 neurons in the mammalian hippocampus. Decades have passed since this landmark observation, yet how the estrous cycle shapes dendritic spine dynamics and hippocampal spatial coding in vivo remains a mystery. Here, we used a custom hippocampal microperiscope and two-photon calcium imaging to track CA1 pyramidal neurons in female mice across multiple cycles. Estrous cycle stage had a potent effect on spine dynamics, with spine density peaking during proestrus when estradiol levels are highest. These morphological changes coincided with greater somatodendritic coupling and increased infiltration of back-propagating action potentials into the apical dendrite. Finally, tracking CA1 response properties during navigation revealed greater place field stability during proestrus, evident at both the single-cell and population levels. These findings demonstrate that the estrous cycle drives large-scale structural and functional plasticity in hippocampal neurons essential for learning and memory.