Neurosteroid modulation of synaptic and GABA-evoked currents in neurons from the rat medial preoptic nucleus

Abstract

The effects of the neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) on synaptic and GABA-evoked currents in acutely dissociated neurons from the medial preoptic nucleus of rat were investigated by perforated-patch recordings under voltage-clamp conditions. The effect of 2.0 microM allopregnanolone on GABA-evoked currents depended strongly on the GABA concentration: the currents evoked by 100 microM GABA were markedly depressed and the desensitization was faster, but the decay after GABA application was prolonged. In contrast, the currents evoked by 1.0 microM GABA were markedly potentiated, the activation was faster, a prominent desensitization was induced, and the decay after GABA application was prolonged. In the absence of externally applied GABA, 2.0 microM allopregnanolone induced a slow current that could be attributed to Cl-. Allopregnanolone did not significantly affect the amplitude of spontaneous tetrodotoxin-insensitive (miniature) synaptic currents (mIPSCs) originating from synaptic terminals releasing GABA onto the dissociated neurons. However, the mIPSC decay phase was dramatically prolonged, with half-maximal effect at approximately 50 nM allopregnanolone. A qualitatively similar effect of allopregnanolone was seen when KCl was used to evoke synchronous GABA release. The frequency of mIPSCs was also affected, on average increased 3.5-fold, by 2.0 microM allopregnanolone, suggesting a presynaptic steroid action.