AN ESSENTIAL ROLE FOR PROTEIN PHOSPHATASES IN HIPPOCAMPAL LONG-TERM DEPRESSION

AN ESSENTIAL ROLE FOR PROTEIN PHOSPHATASES IN HIPPOCAMPAL LONG-TERM DEPRESSION
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DOI:
10.1126/science.8394601
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发表时间:
1993-08-20
期刊:
影响因子:
56.9
通讯作者:
MALENKA, RC
MALENKA, RC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MULKEY, RM;HERRON, CE;MALENKA, RC

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如果不存在降低突触强度的过程,长时程增强(LTP)作为信息储存机制的有效性将受到严重限制。在大鼠海马CA1区,长时间的低频传入刺激引起了一个长期的抑郁症(LTD),这是特定于刺激输入。LTD的诱导被阻断的冈田酸或calyculin A,蛋白磷酸酶1和2A的两种抑制剂的细胞外应用。用微囊藻毒素LR(一种膜不可渗透的蛋白磷酸酶抑制剂)或钙调素拮抗剂加载CA 1细胞也阻断或减弱LTD。在LTD诱导后应用calyculin A逆转了突触抑制,提示磷酸酶活性对LTD的维持是必需的。这些结果表明,突触蛋白磷酸酶的激活在突触的调节中起着重要作用。传输
The effectiveness of long-term potentiation (LTP) as a mechanism for information storage would be severely limited if processes that decrease synaptic strength did not also exist. In area CA1 of the rat hippocampus, prolonged periods of low-frequency afferent stimulation elicit a long-term depression (LTD) that is specific to the stimulated input. The induction of LTD was blocked by the extracellular application of okadaic acid or calyculin A, two inhibitors of protein phosphatases 1 and 2A. The loading of CA1 cells with microcystin LR, a membrane-impermeable protein phosphatase inhibitor, or calmodulin antagonists also blocked or attenuated LTD. The application of calyculin A after the induction of LTD reversed the synaptic depression, suggesting that phosphatase activity is required for the maintenance of LTD. These findings indicate that the synaptic activation of protein phosphatases plays an important role in the regulation of synaptic transmission.