ESTROUS CYCLE MODULATES CORTICAL AUDITORY RESPONSES ACROSS SPECIES

Introduction. Female mammals undergo cyclical physiological and behavioral changes driven by hormonal fluctuations. However, whether and how the estrous cycle modulates auditory sensory processing and the activity of distinct neuronal populations remains poorly understood. Here, we investigated auditory responses across reproductive phases in mice and humans.

Method. We recorded EEG activity in men and women and intracortical local field potentials (LFPs) in male and female mice. Female participants were tested during two phases of their estrous cycle characterized by low estradiol (E2) levels (early follicular phase in women; late estrus in mice) and high E2 levels (late follicular phase in women; proestrus in mice). To assess causality, female mice additionally received systemic injections of estradiol or saline during the late estrus phase.

Results. Across species, females in high-E2 phases exhibited reduced baseline gamma power and weaker auditory entrainment (AE), stimulus-specific adaptation (SSA), and responses to deviant sounds. In female mice during low-E2 phases, acute estradiol administration reduced baseline gamma power, AE, and SSA, supporting a causal role of estradiol in shaping these auditory cortical responses. Single-unit recordings further revealed that baseline firing rates of putative fast-spiking interneurons were selectively increased during high-E2 phases. In addition, both evoked firing rates and spike–LFP coherence during 40-Hz auditory steady-state stimulation were significantly reduced during high-E2 phases.

Conclusions. Together, these findings demonstrate that auditory processing is modulated by estrous cycle across species and highlight the importance of assessing hormonal status when evaluating auditory perception in mouse models and in women with psychiatric disorders.