PKG-mediated MAPK signaling is necessary for long-term operant memory in Aplysia
PKG-mediated MAPK signaling is necessary for long-term operant memory in Aplysia
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DOI：
10.1101/lm.2063611
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发表时间：
2011-02-01
影响因子：
2
通讯作者：
Lyons, Lisa C.
中科院分区：
文献类型：
--
作者：
Michel, Maximilian;Green, Charity L.;Lyons, Lisa C.
记忆形成所需的信号通路，例如丝裂原激活蛋白激酶（MAPK）通路，在物种和范式中似乎高度保守。得知食物不可食用（LFI）代表了一种强大的联想、操作性学习形式，可在海兔中诱导短期记忆（STM）和长期记忆（LTM）。我们研究了 MAPK 信号在体内 LFI 记忆中的作用。训练前抑制动物的 MAPK 激活会阻断 STM 和 LTM。训练后立即停止 MAPK 信号传导会抑制 LTM，但对 STM 没有影响。因此，MAPK 信号传导在 STM 和 LTM 的记忆形成早期似乎是必需的，而 LTM 则需要延长 MAPK 的活性。我们发现 LFI 训练显着增加了颊神经节中磷酸 MAPK 的水平。训练后 MAPK 激活立即明显增加，且高于基础水平持续 2 小时。我们检查了训练诱导的 MAPK 激活的机制，发现 PKG 活性对于 MAPK 激活的延长阶段是必需的，但对于 STM 所需的早期 MAPK 阶段不是必需的。此外，我们发现 MAPK 激活的即时阶段和长期阶段均不依赖于一氧化氮 (NO) 信号传导，尽管如之前报道的那样，记忆的表达依赖于 NO。这些研究强调了 MAPK 和 PKG 在负强化操作记忆中的作用，并证明了 PKG 依赖性 MAPK 信号在无脊椎动物联想记忆中的作用。
Signaling pathways necessary for memory formation, such as the mitogen-activated protein kinase (MAPK) pathway, appear highly conserved across species and paradigms. Learning that food is inedible (LFI) represents a robust form of associative, operant learning that induces short- (STM) and long-term memory (LTM) in Aplysia. We investigated the role of MAPK signaling in LFI memory in vivo. Inhibition of MAPK activation in animals prior to training blocked STM and LTM. Discontinuing MAPK signaling immediately after training inhibited LTM with no impact on STM. Therefore, MAPK signaling appears necessary early in memory formation for STM and LTM, with prolonged MAPK activity required for LTM. We found that LFI training significantly increased phospho-MAPK levels in the buccal ganglia. Increased MAPK activation was apparent immediately after training with greater than basal levels persisting for 2 h. We examined the mechanisms underlying training-induced MAPK activation and found that PKG activity was necessary for the prolonged phase of MAPK activation, but not for the early MAPK phase required for STM. Furthermore, we found that neither the immediate nor the prolonged phase of MAPK activation was dependent upon nitric oxide (NO) signaling, although expression of memory was dependent on NO as previously reported. These studies emphasize the role of MAPK and PKG in negatively reinforced operant memory and demonstrate a role for PKG-dependent MAPK signaling in invertebrate associative memory.