Differential Regulation of Human Paired Associative Stimulation-Induced and Theta-Burst Stimulation-Induced Plasticity by L-type and T-type Ca2+ Channels
Differential Regulation of Human Paired Associative Stimulation-Induced and Theta-Burst Stimulation-Induced Plasticity by L-type and T-type Ca2+ Channels
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DOI：
10.1093/cercor/bhw212
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发表时间：
2017-08-01
期刊：
影响因子：
3.7
通讯作者：
Classen, Joseph
中科院分区：
文献类型：
--
作者：
Weise, David;Mann, Jakob;Classen, Joseph
突触后Ca ~（2+）浓度的活动依赖性变化受多种不同Ca ~（2+）通道的影响，在突触可塑性中起重要作用。配对联合刺激（PAS）和θ脉冲串刺激（TBS）是用于人类受试者的非侵入性磁刺激方案，以诱导持久的皮质脊髓兴奋性变化，其被比作突触长时程增强和长时程抑制。为了更好地表征PAS和TBS诱导的可塑性的Ca 2+相关生理机制，我们研究了不同Ca 2+来源的影响。PAS对皮质脊髓兴奋性的易化作用可被NMDA受体阻断剂美沙芬（DXM）和L型电压门控钙通道（VGCC）阻断剂尼莫地平（NDP）阻断，而被T型VGCC阻断剂乙琥胺（ESM）抑制。虽然，令人惊讶的是，静态皮质脊髓兴奋性增加的DXM和NDP的组合，PAS诱导的促进被阻断。TBS诱导的皮质脊髓兴奋性的促进，其先前已被证明通过L型VGCC阻断剂NDP转变为抑制（Wankerl K，Weise D，Gentner R，Rumpf J，Classen J. 2010. L型电压门控钙通道：人类长时程增强/长时程抑郁样可塑性和活动依赖性后可塑性的单分子开关神经科学杂志30（18）：6197-6204.），被T型VGCC阻断剂ESM阻断，但不逆转。PAS和TBS诱导的可塑性的不同模式的Ca 2+通道调制可能指向PAS诱导的可塑性中的反向传播动作电位的重要作用，类似于在尖峰定时依赖性突触可塑性，并在TBS诱导的可塑性树突状细胞Ca 2+依赖性尖峰的要求。
Activity-dependent changes of postsynaptic Ca2+-concentration are influenced by a variety of different Ca2+-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca2+-related physiological mechanisms underlying PAS-and TBS-induced plasticity, we examined the impact of different Ca2+-sources. PAS-induced facilitation of corticospinal excitability was blocked by NMDA-receptor blocker dextromethorphan (DXM) and L-type voltage gated Ca2+ channels (VGCC) blocker nimodipine (NDP), but turned into depression by T-type VGCC blocker ethosuximide (ESM). Although, surprisingly, static corticospinal excitability was increased by the combination of DXM and NDP, PAS-induced facilitation was blocked. TBS-induced facilitation of corticospinal excitability, which has previously been shown to be turned into depression by L-type VGCC blocker NDP (Wankerl K, Weise D, Gentner R, Rumpf J, Classen J. 2010. 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. J Neurosci. 30(18): 6197-6204.), was blocked, but not reverted, by T-type VGCC blocker ESM. The different patterns of Ca2+-channel modulation of PAS-and TBS-induced plasticity may point to an important role of backpropagating action potentials in PAS-induced plasticity, similar as in spike-timing dependent synaptic plasticity, and to a requirement of dendritic Ca2+-dependent spikes in TBS-induced plasticity.