Progesterone and allopregnanolone facilitate excitatory synaptic transmission in the infralimbic cortex via activation of membrane progesterone receptors

Estrogens and progesterone can have rapid effects on neuronal function and can modify the use of spatial navigation strategies dependent upon the prefrontal cortex, striatum, and hippocampus. Here, we assessed the effects of 17β-estradiol (E2), progesterone, and its metabolite allopregnanolone, on evoked excitatory postsynaptic potentials in the infralimbic region of the female rat prefrontal cortex. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of layer I were first characterized by recording responses at multiple depths between the cortical surface and the underlying white matter. Current source density analysis showed that the short-latency negative component was generated by activation of synaptic currents within layer I, and that putative polysynaptic responses were generated in layers III to V. The amplitude of evoked field EPSPs in layer I was not significantly affected by 20 min application of 17β-estradiol (10 nM), but both 100 nM progesterone and 1 µM allopregnanolone caused lasting increases in field EPSP amplitude. The effects of progesterone were not blocked by the nuclear progesterone receptor antagonist RU486 (1 µM). Both progesterone and allopregnanolone are known to activate membrane progesterone receptors, and we found that the membrane progesterone receptor agonist Org OD 02-0 facilitated EPSPs, and also occluded further increases induced by either progesterone or allopregnanolone. These results provide evidence that both progesterone and allopregnanolone facilitate synaptic responses in layer I of the infralimbic cortex by activating membrane progesterone receptors.