Protein Kinase M Maintains Long-Term Sensitization and Long-Term Facilitation in Aplysia
Protein Kinase M Maintains Long-Term Sensitization and Long-Term Facilitation in Aplysia
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DOI：
10.1523/jneurosci.4744-10.2011
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发表时间：
2011-04-27
影响因子：
5.3
通讯作者：
Glanzman, David L.
中科院分区：
文献类型：
--
作者：
Cai, Diancai;Pearce, Kaycey;Glanzman, David L.
大脑如何维持长期记忆是现代神经科学的主要悬而未决的问题之一。来自哺乳动物研究的证据表明，蛋白激酶 C (PKC) 亚型、蛋白激酶 M zeta (PKM zeta) 的活性在长期记忆的维持中发挥着关键作用。但持久性取决于 PKM zeta 的记忆范围，以及 PKM zeta 对长期记忆影响的机制仍然不清楚。最近，从海兔的神经系统中克隆了一种 PKM 同种型，称为 PKM Apl III。在这里，我们测试了 PKM Apl III 是否在海兔的长期记忆维持中发挥关键作用。血腔内注射假底物抑制肽 ZIP（zeta 抑制肽）或 PKC 抑制剂白屈菜红碱，可消除虹吸回缩反射 (SWR) 的长期敏化 (LTS) 记忆，晚至训练后 7 天。此外，两种 PKM 抑制剂都会破坏感觉运动突触的长期（>= 24 小时）促进 (LTF) 的维持，LTF 是一种突触可塑性形式，之前显示可介导 SWR 的 LTS。与之前的结果（Bougie 等人，2009）一起，我们的结果支持这样的观点：海兔的长期记忆是通过涉及 PKM Apl III 依赖性蛋白磷酸化的正反馈环来维持的。目前的数据将 PKM 在记忆维持中的已知作用扩展到一种简单且经过充分研究的长期学习类型。此外，证明 PKM 活性是海兔感觉运动突触 LTF 持久性的基础，LTF 是一种适合严格细胞和分子分析的突触可塑性形式，应该有助于理解 PKM 活性如何维持记忆。
How the brain maintains long-term memories is one of the major outstanding questions in modern neuroscience. Evidence from mammalian studies indicates that activity of a protein kinase C (PKC) isoform, protein kinase M zeta (PKM zeta), plays a critical role in the maintenance of long-term memory. But the range of memories whose persistence depends on PKM zeta, and the mechanisms that underlie the effect of PKM zeta on long-term memory, remain obscure. Recently, a PKM isoform, known as PKM Apl III, was cloned from the nervous system of Aplysia. Here, we tested whether PKM Apl III plays a critical role in long-term memory maintenance in Aplysia. Intrahemocoel injections of the pseudosubstrate inhibitory peptide ZIP (zeta inhibitory peptide) or the PKC inhibitor chelerythrine erased the memory for long-term sensitization (LTS) of the siphon-withdrawal reflex (SWR) as late as 7 d after training. In addition, both PKM inhibitors disrupted the maintenance of long-term (>= 24 h) facilitation (LTF) of the sensorimotor synapse, a form of synaptic plasticity previously shown to mediate LTS of the SWR. Together with previous results (Bougie et al., 2009), our results support the idea that long-term memory in Aplysia is maintained via a positive-feedback loop involving PKM Apl III-dependent protein phosphorylation. The present data extend the known role of PKM in memory maintenance to a simple and well studied type of long-term learning. Furthermore, the demonstration that PKM activity underlies the persistence of LTF of the Aplysia sensorimotor synapse, a form of synaptic plasticity amenable to rigorous cellular and molecular analyses, should facilitate efforts to understand how PKM activity maintains memory.