A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term potentiation
A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term potentiation
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DOI：
10.1523/jneurosci.2876-05.2005
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发表时间：
2005-11-16
影响因子：
5.3
通讯作者：
Hansel, C
中科院分区：
文献类型：
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作者：
Belmeguenai, A;Hansel, C
小脑平行纤维 (PF)-浦肯野细胞 (PC) 突触可经历突触后表达的长期抑制 (LTD) 或长期增强 (LTP)。 PF-LTD 诱导需要 PF 和 CF（攀爬纤维）输入 PC 的协同活性，以及伴随的钙瞬变和蛋白激酶 C (PKC) 的激活。 PF-LTP 可以单独由 PF 活性诱导，并且其诱导需要比 PF-LTD 更低的钙瞬变。触发 PF-LTP 诱导的细胞事件尚未得到很好的表征。在其他类型的突触（例如海马体）中，双向突触可塑性受到激酶/磷酸酶开关的控制，PKC 和 CaMKII（钙/钙调蛋白依赖性激酶 II）活性促进 LTP 诱导，磷酸酶活性促进 LTD 诱导。在这里，我们使用大鼠小脑切片的全细胞膜片钳记录测试了蛋白磷酸酶 1 (PP1)、PP2A 和 PP2B（钙调神经磷酸酶）在小脑 LTP 诱导中的参与情况。当 PP1/2A 抑制剂冈田酸和微囊藻毒素 LR、PP1 抑制肽抑制剂 2、PP2A 抑制剂福斯特菌素和 PP2B 抑制剂环孢菌素 A 存在时，LTP 诱导被阻断。PKC 抑制剂白屈菜红碱不会损害 LTP 诱导。相反，当将活性 PP2B 注射到 PC 中时，LTD 诱导不会被微囊藻毒素 LR 阻断，反而会减少。这些数据表明激酶/磷酸酶开关控制双向小脑可塑性，但其方式与其他类型突触中发现的依赖性“相反”。因此，小脑 LTP 是迄今为止所描述的唯一依赖于磷酸酶而不是激酶活性的 LTP 形式。
Cerebellar parallel fiber (PF)-Purkinje cell (PC) synapses can undergo postsynaptically expressed long-term depression (LTD) or longterm potentiation (LTP). PF-LTD induction requires the coactivity of the PF and CF (climbing fiber) inputs to PCs and a concomitant calcium transient and activation of protein kinase C (PKC). PF-LTP can be induced by PF activity alone and requires a lower calcium transient for its induction than PF-LTD. The cellular events triggering PF-LTP induction are not well characterized. At other types of synapses (e. g., in the hippocampus), bidirectional synaptic plasticity is under control of a kinase/phosphatase switch, with PKC and CaMKII (calcium/calmodulin-dependent kinase II) activity promoting LTP induction and phosphatase activity promoting LTD induction. Here, we have tested for the involvement of protein phosphatase 1 (PP1), PP2A, and PP2B (calcineurin) in cerebellar LTP induction using whole-cell patch-clamp recordings in rat cerebellar slices. LTP induction was blocked in the presence of the PP1/2A inhibitors okadaic acid and microcystin LR, the PP1 inhibitory peptide inhibitor-2, the PP2A inhibitor fostriecin, and the PP2B inhibitor cyclosporin A. LTP induction was not impaired by the PKC inhibitor chelerythrine. Conversely, LTD induction was not blocked by microcystin LR but instead was reduced when active PP2B was injected into PCs. These data indicate that a kinase/phosphatase switch controls bidirectional cerebellar plasticity, but in a manner "inverse" to the dependencies found at other types of synapses. Therefore, cerebellar LTP constitutes the only form of LTP described so far that depends on phosphatase rather than kinase activity.