Membrane progesterone and oestrogen receptors modulate GABAergic transmission in the prefrontal cortex of prepubertal male, but not female, mice

The sex hormones progesterone (P) and oestrogen (E) reorganize GABAergic transmission in the prefrontal cortex (PFC) during the transition from childhood to adolescence, generating a new excitatory-inhibitory balance necessary for the computational capacity of the mature PFC. Little is known, however, about the hormone receptors involved or whether there are sex differences in the modulation of GABAergic transmission they exert. We hypothesize that P and E can rapidly (within minutes) modulate GABAergic currents through G protein-coupled receptors, namely membrane P receptors (mPRs) and the G protein-coupled E receptor (GPER), respectively, in PFC. First, we quantified the expression of P and E receptors in PFC using quantitative RT-PCR. Secondly, we recorded synaptic (phasic) and extrasynaptic (tonic) GABAergic currents in basal conditions and in response to the activation of mPRs and GPER using patch-clamp recordings in PFC neurons of prepubertal female and male mice. Expression levels of mPRs differed in the PFC of females and males, but no differences were found in the basal levels of phasic or tonic GABAergic currents between sexes. Interestingly, selective activation of mPRs increased tonic GABAergic transmission in males but not in females, and activation of GPER increased phasic GABAergic transmission only in males. We also demonstrated that GABAergic modulation exerted by mPRs and GPER was dependent on protein kinase A and C. This study sheds light on new mechanisms by which P and E can rapidly modulate GABAergic transmission in PFC neurons through the activation of mPRs and GPER.