Department of Neurobiology, The Weizmann Institute, 76100 Rehovot, Israel.
Hippocampus. 2012 Feb;22(2):267-75. doi: 10.1002/hipo.20893. Epub 2010 Nov 15.
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.
腹侧海马体 (VH) 最近被证明其长时程增强 (LTP) 的幅度低于背侧海马体 (DH)。急性应激暴露消除了这种差异，应激大鼠的 VH 切片产生的 LTP 比 DH 中产生的 LTP 更大，而应激则降低了 DH 中的 LTP。为了揭示导致这种差异作用的机制，我们发现醛固酮激活盐皮质激素受体 (MR) 可模拟应激对 VH 的作用，促进 LTP。我们还发现醛固酮降低了 DH 和 VH 中的 GABA 能抑制。我们现在检查了 MR 引起的抑制减少是否可以作为 VH 中 LTP 改变的基础。在暴露于 GABA 拮抗剂荷包牡丹碱和醛固酮之前和之后，记录大鼠海马切片。正如预期的那样，用荷包牡丹碱阻断 GABA 增强了 DH 和 VH 中的 LTP。然而，它的作用并没有掩盖醛固酮在 VH 中的作用，表明后者药物不是通过阻断抑制起作用的。此外，NMDA 受体拮抗剂 APV 阻断了在荷包牡丹碱存在下诱导的 LTP，但没有阻断醛固酮引起的 LTP 促进作用，表明醛固酮的作用不是通过常规的 NMDA 依赖性 LTP 产生机制介导的。此外，醛固酮对 LTP 的快速作用被 L 型钙通道拮抗剂硝苯地平阻断，表明醛固酮通过硝苯地平敏感通道促进钙内流，以增强 VH 中的 LTP。醛固酮作用的部位可能是突触前终端，因为它导致 VH 中配对脉冲增强明显增强，但在 DH 中没有增强。这些实验证实并扩展了以前关于 MR 对海马神经元可塑性影响的建议。
