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

Neurosteroid modulation of synaptic and GABA-evoked currents in neurons from the rat medial preoptic nucleus. J. Neurophysiol. 82. 143-151, 1999. The effects of the neurosteroid 3 alpha-hydroxy-5 alpha-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 mu M allopregnanolone on GABA-evoked currents depended strongly on the GABA concentration: the currents evoked by 100 mu M 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 mu M GABA were markedly potentiated, the activation was faster, a prominent desensitization was induced, and the Je,,decay after GABA application was prolonged. In the absence of externally applied GABA 2.0 mu M allopreqnanolone 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 similar to 50 nM allopregnanolone A qualitatively similar effect of allopregnanolone was seen when KCI was used to evoke synchronous GABA release. The frequency of mIPSCs was also affected, on average increased 3.5-fold, by 2.0 mu M allopregnanolone, suggesting a presynaptic steroid action.