Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Learn Mem. 2011 Aug 15;18(9):545-53. doi: 10.1101/lm.2252511. Print 2011.
Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre- and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We examined plasticity following the pairing of spike trains in the touch mechanosensory neuron (T cell) and S interneuron (S cell) in the medicinal leech. Long-term potentiation (LTP) of T to S signaling was elicited when the T-cell spike train preceded the S-cell train. An interval 0 to +1 sec between the T- and S-cell spike trains was required to elicit long-term potentiation (LTP), and this potentiation was NMDA receptor (NMDAR)-dependent. Long-term depression (LTD) was elicited when S-cell activity preceded T-cell activity and the interval between the two spike trains was -0.2 sec to -10 sec. This surprisingly broad temporal window involved two distinct cellular mechanisms; an NMDAR-mediated LTD (NMDAR-LTD) when the pairing interval was relatively brief (<-1 sec) and an endocannabinoid-mediated LTD (eCB-LTD) when longer pairing intervals were used (-1 to -10 sec). This eCB-LTD also required activation of a presynaptic transient receptor potential vanilloid (TRPV)-like receptor, presynaptic Ca(2+) release from intracellular stores and activation of voltage-gated Ca(2+) channels (VGCCs). These findings demonstrate that the pairing of spike trains elicits timing-dependent forms of LTP and LTD that are supported by a complex set of cellular mechanisms involving NMDARs and endocannabinoid activation of TRPV-like receptors.
突触信号的持续、双向变化（即突触的增强和抑制）可以通过单个突触前和突触后动作电位的精确时间来诱导。然而，人们对动作电位偶联串引发持续增强或抑制的能力关注甚少。我们在医用水蛭的触摸机械感觉神经元（T 细胞）和 S 中间神经元（S 细胞）中检查了尖峰串对后的可塑性。当 T 细胞尖峰串在前，S 细胞尖峰串在后时，会引发 T 到 S 信号的长时程增强（LTP）。在 T 和 S 细胞尖峰串之间需要 0 到 +1 秒的间隔才能引发长时程增强（LTP），这种增强依赖于 NMDA 受体（NMDAR）。当 S 细胞活动先于 T 细胞活动，并且两个尖峰串之间的间隔为-0.2 秒至-10 秒时，会引发长时程抑制（LTD）。这个令人惊讶的宽时间窗口涉及两个不同的细胞机制；当配对间隔相对较短（<-1 秒）时，涉及 NMDA 受体介导的 LTD（NMDAR-LTD），当使用较长的配对间隔时（-1 到-10 秒），涉及内源性大麻素介导的 LTD（eCB-LTD）。这种 eCB-LTD 还需要激活一个位于突触前的瞬时受体电位香草酸（TRPV）样受体，来自细胞内储存的突触前 Ca2+释放，以及激活电压门控 Ca2+通道（VGCCs）。这些发现表明，尖峰串的偶联引发了依赖时间的 LTP 和 LTD 形式，这些形式由涉及 NMDA 受体和内源性大麻素激活 TRPV 样受体的一系列复杂细胞机制支持。
