Figure 5.
Pharmacological treatments aimed at increasing or inhibiting neurosteroidogenesis affect mixed GABAA/glycine mIPSC synaptic transmission. Neurons were recorded in the absence of any inhibitory amino acid receptor antagonists at a holding potential of –60 mV. Histograms give the percentage of mixed GABAA/GlyR mIPSCs recorded among the overall population of mIPSCs in immature (<P23) (left histogram) and adult neurons (>P30) (right histogram). AP (100 nm) and DZP (1μm) were applied by superfusion. Other treatments consisted of short-time (<1 hr) and/or prolonged (>1 hr) incubation of slices with FLU (10μm), FIN (50μm), PK11195 (PK) (10μm), diazepam plus flumazenil (DZP+FLU), and diazepam plus flumazenil plus PK11195 (DZP+FLU+PK). A significant increase in the proportion of mixed GABAA/glycine mIPSCs was noted in the presence of AP, DZP, and DZP+FLU (>1 hr) in immature slices. Conversely, a large reduction was noted with PK11195 or finasteride, two inhibitors of neurosteroidogenesis. After 30 d of postnatal life (>P30), no mixed events were detected. However, such mixed events reappeared in the presence of AP, DZP, or DZP+FLU (>3 hr). Incubation with finasteride (>6 hr) never revealed mixed mIPSCs. Asterisks represent statistically significant differences (t test; p < 0.05).