17 β-estradiol modulates GABAergic synaptic transmission and tonic currents during development in vitro

Estrogens exert a variety of modulatory effects on the structure and function of the nervous system. In particular, 17 β-estradiol was found to affect GABAergic inhibition in adult animals but its action on GABAergic currents during development has not been elucidated. In the present study, we investigated the effect of 17 β-estradiol on hippocampal neurons developing in vitro. In this model, mIPSC kinetics showed acceleration with age along with increased α1 subunit expression, similarly as in vivo. Long-term treatment with 17 β-estradiol increased mIPSC amplitudes in neurons cultured for 6–8 and 9–11DIV and prolonged the mIPSC decaying phase only in the 9–11DIV group. The time needed for the onset of 17 β-estradiol effect on mIPSC amplitude was approximately 48h. In the period of 9–11DIV, treatment with 17 β-estradiol strongly reduced the tonic conductance activated by low GABA concentrations. The effects of 17 β-estradiol on mIPSCs and tonic conductance were not correlated with any change in expression of considered GABAAR subunits (α1–3, α5–6, γ2) while α4 and δ subunits were at the detection limit. In conclusion, we provide evidence that 17 β-estradiol differentially affects the phasic and tonic components of GABAergic currents in neurons developing in vitro.