Long-Term Potentiation at Cerebellar Parallel Fiber–Purkinje Cell Synapses Requires Presynaptic and Postsynaptic Signaling Cascades
Long-Term Potentiation at Cerebellar Parallel Fiber–Purkinje Cell Synapses Requires Presynaptic and Postsynaptic Signaling Cascades
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DOI：
10.1523/jneurosci.4064-13.2014
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发表时间：
2014-02
期刊：
影响因子：
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通讯作者：
De-Juan Wang;Li-da Su;Ya‐Nan Wang;Dong Yang;Cheng-long Sun;Lin Zhou;Xin-xin Wang;Ying Shen
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文献类型：
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作者：
De-Juan Wang;Li-da Su;Ya‐Nan Wang;Dong Yang;Cheng-long Sun;Lin Zhou;Xin-xin Wang;Ying Shen
小脑平行纤维浦肯野细胞 (PF-PC) 突触的长时程抑制 (LTD) 和长时程增强 (LTP) 在运动学习中发挥着关键作用。 PF-PC 突触处的 1 Hz 刺激会诱导突触后表达的 LTP，需要突触后 Ca2+ 瞬态、磷酸酶和一氧化氮 (NO)。然而，1 Hz PF-LTP 的潜在机制仍不清楚，因为没有一个已知事件彼此相关。在这里，我们证明 1 Hz PF-LTP 需要突触后胞浆磷脂酶 A2 α (cPLA2α)/花生四烯酸 (AA) 信号传导和突触前内源性大麻素受体。使用小脑切片中的膜片钳记录，我们发现 1 Hz PF-LTP 在 cPLA2α 敲除小鼠中被废除。 1 Hz PF 刺激和局部应用 AA 的结合有效地弥补了这一缺陷。 2-花生四烯酰甘油和大麻素受体 1 (CB1R) 的逆行激活也参与 1 Hz LTP，因为它被 2-AG 水解或抑制 CB1R 所阻断。使用培养颗粒细胞和PF端子中的NO电极检测释放的NO量。我们的结果表明，PF 末端 CB1R 的激活激活了 NO 合成酶并促进了 NO 的产生。 1 Hz PF 刺激引起有限的 NO，但 100 Hz PF 刺激产生大量 NO。因此，1 Hz PF-LTP 与经典的突触后表达可塑性不同，需要同时发生的突触前和突触后活动。此外，足够幅度的NO决定PF-PC突触的减弱和增强。
Long-term depression (LTD) and long-term potentiation (LTP) at cerebellar parallel fiber-Purkinje cell (PF-PC) synapses play critical roles in motor learning. The 1 Hz stimulation at PF-PC synapses induces a postsynaptically expressed LTP that requires a postsynaptic Ca2+ transient, phosphatases, and nitric oxide (NO). However, the mechanism underlying 1 Hz PF-LTP remains unclear because none of the known events is related to each other. Here, we demonstrated that 1 Hz PF-LTP requires postsynaptic cytosolic phospholipase A2 α (cPLA2α)/arachidonic acid (AA) signaling and presynaptic endocannabinoid receptors. Using patch-clamp recording in cerebellar slices, we found that 1 Hz PF-LTP was abolished in cPLA2α-knock-out mice. This deficit was effectively rescued by the conjunction of 1 Hz PF stimulation and the local application of AA. 2-Arachidonoylglycerol and the retrograde activation of cannabinoid receptor 1 (CB1R) were also involved in 1 Hz LTP because it was blocked by the hydrolysis of 2-AG or by inhibiting CB1Rs. The amount of NO released was detected using an NO electrode in cultured granule cells and PF terminals. Our results showed that the activation of CB1Rs at PF terminals activated NO synthetase and promoted NO production. The 1 Hz PF-stimuli evoked limited NO, but 100 Hz PF stimulation generated a large amount. Therefore, 1 Hz PF-LTP, distinct from classical postsynaptically expressed plasticity, requires concurrent presynaptic and postsynaptic activity. In addition, NO of sufficient amplitude decides between the weakening and strengthening of PF-PC synapses.