Estrus-Cycle Regulation of Cortical Inhibition

Female mammals experience cyclical changes in sexual receptivity known as the estrus cycle. Little is known about how estrus affects the cortex, although alterations in sensation, cognition and the cyclical occurrence of epilepsy suggest brain-wide processing changes. We performed in vivo juxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus cycle potently altered cortical inhibition. Fast-spiking interneurons were strongly activated with social facial touch and varied their ongoing activity with the estrus cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change. In situ hybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive (PV+) interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings. The fraction of neurons positive for estrogen receptor β (Esr2) and PV co-localization (Esr2⁺PV⁺) in cortical layer V was increased in proestrus. In vivo and in vitro experiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen-receptor-β-dependent mechanism.