Age-dependent, steroid-specific effects of oestrogen on long-term potentiation in rat hippocampal slices

1. Long-term potentiation (LTP) of hippocampal population spike responses a nd excitatory postsynaptic potentials (EPSPs) from area CA1 stratum pyramid ale was induced in slices of rat hippocampus maintained in vitro following brief high-frequency stimulation (HPS) of the Schaffer collateral-commissur al pathway. When administered to slices prior to HFS, 17 beta-oestradiol (O E2), at a concentration as low as 0.1 nM, suppressed the magnitude of the r esultant HFS-induced potentiation in slices from prepubertal animals (3 and 4 weeks old) of both sexes. 2. OE2 did not suppress the induction of LTP in slices taken from the hippo campus of adult animals of either sex. 3. There was no similar suppressant effect of 17 alpha-oestradiol (OE1), pr ogesterone (PRG) or testosterone (TST) on LTP in the young animals, even at a concentration 100 times greater than was effective for OE2. 4. The anti-oestrogen compound tamoxifen (TMX; 1.0 and 10.0 mu M), which ac ts principally at intracellular binding sites within the nucleus, was witho ut effect in diminishing the suppressant effect of OE2 on LTP in slices fro m young animals. 5. The LTP observed in slices from both 3-week-old and adult rats was AP5 s ensitive and thus was shown to be dependent on activation of NMDA receptors . Results from whole-cell recording experiments suggested that OE2 caused t he LTP-suppressant effect through an action on NMDA-mediated currents. 6. These data suggest an age-dependent and possibly a surface membrane rece ptor-mediated role for oestrogens in modulating the efficacy of input-outpu t properties of CA1 neurones produced by HFS during a critical period in de velopment.