Song D, Xie X, Wang Z, Berger T W
Department of Biomedical Engineering, University of Southern California, Los Angeles 90089, USA.
Neurobiol Learn Mem. 2001 Nov;76(3):375-87. doi: 10.1006/nlme.2001.4032.
The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni2+ (50 microM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni2+ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 microM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni2+. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni2+. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.
在体外实验中，比较了四乙铵（TEA）和高频刺激（HFS）诱导长期突触修饰的效果。高频刺激可在穿通通路 - 齿状回颗粒细胞突触和海马体CA1区锥体细胞的Schaffer侧支突触处诱导长时程增强（LTP）。相比之下，25 mM的TEA在齿状回诱导长时程抑制（LTD），而在CA1区诱导LTP。研究了TEA在CA1区和齿状回产生不同作用的潜在机制。观察到T型电压依赖性钙通道（VDCC）阻滞剂Ni2 +（50 μM）可部分阻断TEA在CA1区诱导的LTP。当Ni2 +与NMDA受体拮抗剂D - APV联合应用时，可完全阻断TEA诱导的LTP。L型VDCC阻滞剂硝苯地平（20 μM）对CA1区TEA诱导的LTP无影响。在同一切片中的齿状回，TEA实际上诱导了长时程抑制（LTD）而非LTP，该效应可被D - APV阻断。T型和L型VDCC的阻断均不能阻止这种LTD。当灌注培养基中的钙浓度增加时，TEA在齿状回诱导出一种弱的LTP，该LTP可被Ni2 +阻断。在暴露于TEA期间，CA1区和齿状回的场兴奋性突触后电位（fEPSP）幅度均增加，但CA1区的增加幅度更大。应用四乙铵还与CA1区一个大的、晚期的兴奋性突触后电位成分相关，即使切断CA3和CAI之间的联系后该成分仍持续存在。然而，Ni2 +可显著降低TEA在CA1区的所有效应。本研究结果表明，TEA在CA1区通过T型VDCC和NMDA受体间接发挥作用，从而诱导LTP。相比之下，TEA在齿状回仅通过NMDA受体间接发挥作用并导致LTD。这些结果增加了大鼠海马体CA1区和齿状回中T型VDCC和NMDA受体密度和/或分布存在主要突触差异的可能性。
