Progesterone modulates theta oscillations in the frontal-parietal network.

The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognition, yet, the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern, often related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration of P4 and T using salivary enzyme immunoassay and FMT oscillations using high-density electroencephalography (EEG) during eyes-open resting-state in 55 healthy women and men. Electrical brain activity was analyzed using Fourier analysis, aperiodic signal fitting, and beamformer source localization. Steroid hormone concentrations and biological sex were used as predictors for scalp and source-estimated amplitude of theta oscillations. Elevated concentrations of P4 predicted increased amplitude of FMT oscillations across both sexes, and no relationship was found with T. The positive correlation with P4 was specific to the frontal midline electrodes and survived correction for the background aperiodic signal of the brain. Using source localization, FMT oscillations were localized to the frontal-parietal network (FPN). Additionally, theta amplitude within the FPN, but not the default mode network, positively correlated with P4 concentration. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the FPN.

Transplantation of GABAergic Interneurons into the Neonatal Primary Visual Cortex Reduces Absence Seizures in Stargazer Mice.

Epilepsies are debilitating neurological disorders characterized by repeated episodes of pathological seizure activity. Absence epilepsy (AE) is a poorly understood type of seizure with an estimated 30% of affected patients failing to respond to antiepileptic drugs. Thus, novel therapies are needed for the treatment of AE. A promising cell-based therapeutic strategy is centered on transplantation of embryonic neural stem cells from the medial ganglionic eminence (MGE), which give rise to gamma-aminobutyric acidergic (GABAergic) interneurons during embyronic development. Here, we used the Stargazer (Stg) mouse model of AE to map affected loci using c-Fos immunohistochemistry, which revealed intense seizure-induce activity in visual and somatosensory cortices. We report that transplantation of MGE cells into the primary visual cortex (V1) of Stg mice significantly reduces AE episodes and lowers mortality. Electrophysiological analysis in acute cortical slices of visual cortex demonstrated that Stg V1 neurons exhibit more pronounced increases in activity in response to a potassium-mediated excitability challenge than wildtypes (WT). The defective network activity in V1 was significantly altered following WT MGE transplantation, associating it with behavioral rescue of seizures in Stgs. Taken together, these findings present MGE grafting in the V1 as a possible clinical approach in the treatment of AE.