Abstract

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid‐luteal phase when progesterone and estradiol are highest, and early follicular phase when progesterone and estradiol are lowest. Significantly higher (∼5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modeling, these changes were linked to stronger self‐inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition, the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma‐band oscillations.

Highlights

  • Over the course of the menstrual cycle, changes in the GABA system are modulated primarily by the major metabolite of progesterone, allo-In healthy women, fluctuations in gonadal hormones lead to functional pregnanolone

  • As the primary mediator of cortical inhibition, the g-aminobutyric acid (GABA) system and aberrant GABAergic inhibition has been implicated in these menstrual cycle related disorders (Bäckstro€m et al, 2003)

  • By binding to the neurosteroidal site on the GABAA receptor allopregnanolone potentiates the effect of GABA, leading to an overall increase in inhibition of neuronal excitability (Birzniece et al, The authors have no conflicts of interest to declare. 2006; Majewska, Harrison, Schwartz, Barker, & Paul, 1986)

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Summary

Introduction

Over the course of the menstrual cycle, changes in the GABA system are modulated primarily by the major metabolite of progesterone, allo-In healthy women, fluctuations in gonadal hormones lead to functional pregnanolone. Allopregnanolone, similar to benzodiazepines, produces changes in the brain over the course of each menstrual cycle The this change via its action as a potent positive allosteric modulator of interaction of these hormones with the balance of cortical excitation and inhibition has formed the basis of research attempting to characthe GABAA receptor. This mechanism of action, in combination with the readiness with which progesterone and its metabolites cross the terize changes across both the healthy menstrual cycle and menstrual blood brain barrier (around 83% for progesterone (Pardridge & Mietus, cycle linked disorders, such as catamenial epilepsy and premenstrual 1979) has led to research into allopregnanolone’s use as a central dysphoric disorder (PMDD) (Bäckstro€m et al, 2014; Reddy, 2004). By binding to the neurosteroidal site on the GABAA receptor allopregnanolone potentiates the effect of GABA, leading to an overall increase in inhibition of neuronal excitability

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