L-Type Voltage-Gated Ca2+ Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans
L-Type Voltage-Gated Ca2+ Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans
复制标题
DOI：
10.1523/jneurosci.4673-09.2010
复制
发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
K. Wankerl;D. Weise;R. Gentner;Jost-Julian Rumpf;J. Classen
中科院分区：
文献类型：
--
作者：
K. Wankerl;D. Weise;R. Gentner;Jost-Julian Rumpf;J. Classen
突触经历持续活动依赖的增强或抑制[长时程增强(LTP)/长时程抑制(LTD)]的能力可能会被先前的神经元活动深刻地改变。虽然自然的神经元活动可以在体内进行实验操作，但对LTP/LTD模型中参与调节这种变态的体内生理机制知之甚少。为了研究钙信号是否可能影响人体体内的化生可塑性，我们使用了连续theta Burst刺激(CTBS)(Huang等人，2005年)，这是一种无创性的新型重复磁刺激方案，已知的是诱导皮质脊髓兴奋性的持续性改变，其极性被先前的自愿运动活动改变。当针对初级运动皮质时，CTBS引起皮质脊髓兴奋性的长时间增强，但受L电压门控性钙通道拮抗剂尼莫地平的影响而抑制。这两种后遗症都被NMDA受体拮抗剂右美沙芬阻断，支持了动物研究中观察到的这些双向CTBS诱导的皮质脊髓兴奋性的改变映射到LTP和LTD的观点。短时间自主收缩和小剂量NDP均不能阻断CTBS诱导的增强效应。然而，当两种干预措施联合使用时，会诱发抑郁，并且这种抑郁的程度随着NDP剂量的增加而增加。这些发现表明，钙离子动力学决定了体内LTP/LTD样变化的极性。L-VGCCs可能作为分子开关介导内源性神经元激活诱导的化生。
The ability of synapses to undergo persistent activity-dependent potentiation or depression [long-term potentiation (LTP)/long-term depression (LTD)] may be profoundly altered by previous neuronal activity. Although natural neuronal activity can be experimentally manipulated in vivo, very little is known about the in vivo physiological mechanisms involved in regulating this metaplasticity in models of LTP/LTD. To examine whether Ca2+ signaling may influence metaplasticity in vivo in humans, we used continuous theta burst stimulation (cTBS) (Huang et al., 2005), a noninvasive novel repetitive magnetic stimulation protocol known to induce persistent alterations of corticospinal excitability whose polarity is changed by previous voluntary motor activity. When directed to the naive motor cortex, cTBS induced long-lasting potentiation of corticospinal excitability, but depression under the influence of nimodipine (NDP), an L-type voltage-gated Ca2+ channel (L-VGCC) antagonist. Both aftereffects were blocked by dextromethorphan, an NMDA receptor antagonist, supporting the notion that these bidirectional cTBS-induced alterations of corticospinal excitability map onto LTP and LTD as observed in animal studies. A short period of voluntary contraction and a small dose of NDP were each ineffective in blocking the cTBS-induced potentiation. However, when both interventions were combined, a depression was induced, and the magnitude of this depression increased with the dose of NDP. These findings suggest that Ca2+ dynamics determine the polarity of LTP/LTD-like changes in vivo. L-VGCCs may act as molecular switches mediating metaplasticity induced by endogenous neuronal activation.