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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning.
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Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning.

机译：长期记忆所需的蛋白质合成是在联想学习之前的几天由PKC激活诱导的。

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摘要

Protein synthesis has long been known to be required for associative learning to consolidate into long-term memory. Here we demonstrate that PKC isozyme activation on days before training can induce the synthesis of proteins necessary and sufficient for subsequent long-term memory consolidation. Bryostatin (Bryo), a macrolide lactone with efficacy in subnanomolar concentrations and a potential therapeutic for Alzheimer's disease, is a potent activator of PKC, some of whose isozymes undergo prolonged activation after associative learning. Under normal conditions, two training events with paired visual and vestibular stimuli cause short-term memory of the mollusc Hermissenda that lasts approximately 7 min. However, after 4-h exposures to Bryo (0.25 ng/ml) on two preceding days, the same two training events produced long-term conditioning that lasted >1 week and that was not blocked by anisomycin (1 mug/ml). Anisomycin, however, eliminated long-term memory lasting at least 1 week after nine training events. Both the nine training events alone and two Bryo exposures plus two training event regimens caused comparably increased levels of the PKC alpha-isozyme substrate calexcitin in identified type B neurons and enhanced PKC activity in the membrane fractions. Furthermore, Bryo increased overall protein synthesis in cultured mammalian neurons by up to 60% for >3 days. The specific PKC antagonist Ro-32-0432 blocked much of this Bryo-induced protein synthesis as well as the Bryo-induced enhancement of the behavioral conditioning. Thus, Bryo-induced PKC activation produces those proteins necessary and sufficient for long-term memory on days in advance of the training events themselves.
机译：长期以来，人们一直认为蛋白质合成是整合学习以巩固长期记忆所必需的。在这里，我们证明了训练前几天的PKC同工酶激活可以诱导合成蛋白质，这些蛋白质对于后续的长期记忆巩固是必要和足够的。 Bryostatin（Bryo）是一种大环内酯类内酯，在纳摩尔浓度以下具有效力，并且是阿尔茨海默氏病的潜在治疗剂，是PKC的有效激活剂，在联合学习后，其中的一些同工酶会长时间激活。在正常条件下，两次视觉和前庭刺激相结合的训练事件会导致软体动物Hermissenda的短期记忆，持续大约7分钟。然而，在前两天暴露于Bryo（0.25 ng / ml）中4小时后，相同的两次训练事件产生了持续时间大于1周的长期调理，并且不受茴香霉素（1杯/ ml）的阻断。然而，安尼霉素消除了九次训练事件后至少持续1周的长期记忆。单独的九次训练事件和两次Bryo暴露加两次训练事件方案都导致在确定的B型神经元中PKCα-同工酶底物钙excitin的水平相对增加，并且膜级分中的PKC活性增强。此外，Bryo将培养的哺乳动物神经元中的总蛋白质合成提高了60％，持续了超过3天。特定的PKC拮抗剂Ro-32-0432阻止了这种Bryo诱导的蛋白质合成以及Bryo诱导的行为调节增强。因此，Bryo诱导的PKC激活会在训练事件本身之前的几天产生长期记忆所必需和足够的蛋白质。

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