The ovarian cycle and estradiol modulate cortical network state and auditory entrainment in mice and women

The human brain is a dynamic organ that constantly adapts to both internal and external stimuli over varying timescales. Sex hormones, such as estradiol (E2), play a crucial role in influencing behavioral and physiological changes in both male and female brains. The ovarian cycle, a natural model in female mammals, offers insights into how hormones like E2 affect cellular and network states to modulate brain function.

Researchers sought to determine whether the ovarian cycle impacts sensory cortical processing in both mice and humans. To achieve this, they recorded EEG activity in men and women, as well as intracortical local field potentials in male and female mice, during two distinct phases of the ovarian cycle. In females, these phases were the early follicular phase, marked by low E2 levels, and the late follicular phase, characterized by high E2 levels.

Similarly, in mice, the phases were late estrus and proestrus, respectively. Both human participants and mice were tested during these two ovarian cycle phases.

The study found that high levels of estradiol, whether naturally occurring or artificially administered, were associated with a steeper aperiodic power spectral slope, indicating a decrease in the balance between excitatory and inhibitory activity in the brain. This reduction in excitatory/inhibitory drive also led to attenuated auditory entrainment following a 40Hz stimulation.

At the cellular level, high E2 selectively increased the baseline and sustained 40-Hz firing of putative fast-spiking interneurons, while simultaneously reducing their temporal coherence during both spontaneous and stimulus-evoked activity. This suggests that E2 enhances inhibitory tone, but disrupts the coordination of inhibitory networks.

Overall, the findings reveal that estradiol dynamically modulates cortical network states and auditory responsiveness. This underscores the importance of investigating the intricate relationship between hormones and the brain as a fundamental model for understanding sex-specific neurobiology.