Cellular basis of a rapid effect of mineralocorticosteroid receptors activation on LTP in ventral hippocampal slices.

The ventral hippocampus (VH) was recently shown to express lower magnitude LTP compared to the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. In an attempt to uncover the mechanisms responsible for this differential action, we found that activation of mineralocorticosteroid receptors (MR) by aldosterone mimics the effects of stress in the VH, to facilitate LTP. We also found that aldosterone reduces GABAergic inhibition in both the DH and VH. We now examined if the reduction in inhibition caused by MRs can underlie the altered LTP in the VH. Rat hippocampal slices were recorded before and after exposure to the GABA antagonist bicuculline and to aldosterone. As expected, blockade of GABA with bicuculline enhanced LTP in both DH and VH. However, its effect did not occlude that of aldosterone in the VH, indicating that the latter drug does not operate by blockade of inhibition. Furthermore, the NMDA receptor antagonist APV blocked LTP induced in the presence of bicuculline, but did not block LTP facilitation by aldosterone, indicating that the effect of aldosterone is not mediated by the conventional NMDA-dependent LTP generating mechanism. Furthermore, rapid effects of aldosterone on LTP were blocked by the L-type calcium channel antagonist nifedipine, indicating that aldosterone facilitates calcium influx via nifedipine-sensitive channels, to enhance LTP in the VH. The locus of effect of aldosterone may be the presynaptic terminal, as it caused a marked facilitation of paired pulse potentiation in the VH but not in the DH. These experiments confirm and extend previous suggestions for the effects of MRs on neuronal plasticity in the hippocampus.