CAMP CONTRIBUTES TO MESSY FIBER LTP BY INITIATING BOTH A COVALENTLY MEDIATED EARLY PHASE AND MACROMOLECULAR SYNTHESIS-DEPENDENT LATE-PHASE

CAMP CONTRIBUTES TO MESSY FIBER LTP BY INITIATING BOTH A COVALENTLY MEDIATED EARLY PHASE AND MACROMOLECULAR SYNTHESIS-DEPENDENT LATE-PHASE
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DOI:
10.1016/0092-8674(94)90401-4
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发表时间:
1994-10-07
期刊:
影响因子:
64.5
通讯作者:
KANDEL, ER
KANDEL, ER
中科院分区:
生物学1区
文献类型:
--
作者:
HUANG, YY;LI, XC;KANDEL, ER

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记忆储存有一个短期阶段,依赖于预先存在的蛋白质,以及一个长期阶段,需要新的蛋白质和RNA合成。海马长时程增强(LTP)被认为有助于记忆储存。与这一想法一致,这些阶段的细胞代表性已在NMDA受体依赖性LTP中得到证实。相比之下,人们对凌乱纤维途径的非NMDA受体依赖性LTP知之甚少。我们发现杂乱纤维LTP也有阶段性。只有晚期被蛋白质和RNA合成抑制剂阻断,但两个阶段都被cAMP依赖性蛋白激酶抑制剂阻断,并且都被毛喉素和Sp-cAMPS刺激。在早期阶段,成对脉冲易化被阻断。这种闭塞随着晚期相的开始而衰减,与其使用不同的机制一致。因此,尽管Schaffer侧枝和苔藓纤维通路在早期阶段使用非常不同的机制,但在晚期阶段两者都使用cAMP介导的机制。
Memory storage has a short-term phase that depends on preexisting proteins and a long-term phase that requires new protein and RNA synthesis. Hippocampal long-term potentiation (LTP) is thought to contribute to memory storage. Consistent with this idea, a cellular representation of these phases has been demonstrated in NMDA receptor-dependent LTP. By contrast, little is known a bout the NMDA receptor-independent LTP of the messy fiber pathway. We find that messy fiber LTP also has phases. Only late phase is blocked by protein and RNA synthesis inhibitors, but both phases are blocked by inhibitors of cAMP-dependent protein kinase, and both are stimulated by forskolin and Sp-cAMPS. During early phase, paired-pulse facilitation is occluded. This occlusion decays with the onset of late phase, consistent with its using a different mechanism. Thus, although Schaffer collateral and mossy fiber pathways use very different mechanisms for early phase, both use a cAMP-mediated mechanism far late phase.