Different phases of long-term memory require distinct temporal patterns of PKA activity after single-trial classical conditioning
Different phases of long-term memory require distinct temporal patterns of PKA activity after single-trial classical conditioning
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DOI：
10.1101/lm.1088408
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发表时间：
2008-09-01
影响因子：
2
通讯作者：
Kemenes, Gyoergy
中科院分区：
文献类型：
--
作者：
Michel, Maximilian;Kemenes, Ildiko;Kemenes, Gyoergy
cAMP依赖性蛋白激酶（PKA）在转录非依赖性短期或中期记忆和转录依赖性长期记忆（LTM）中起关键作用。虽然不同的LTM阶段已经在一些系统中得到了证明，但尚不清楚这些阶段是否需要不同的学习诱导PKA激活的时间模式。这个问题得到了解决，在一个强大的形式的联想LTM出现在几个小时后，单试验食物奖励经典条件反射的池塘蜗牛滞水。在建立了PKA催化亚基的分子和功能的身份，在神经系统中，我们使用PKA活性测量和抑制技术相结合，以研究其在LTM在完整的动物。PKA活性在参与单次学习的神经节中表现出短的潜伏期，但经典条件反射后延长增加。然而，虽然训练后立即（0-10分钟）增加PKA活性对于LTM的早期阶段（6小时）是必不可少的，但LTM的晚期阶段（24小时）需要PKA活性的长期增加。这些观察结果表明PKA在LTM的最近和更远阶段中的机制不同的作用，这可能是这些阶段所需的不同细胞和分子机制的基础。
The cAMP-dependent protein kinase (PKA) is known to play a critical role in both transcription-independent short-term or intermediate-term memory and transcription-dependent long-term memory (LTM). Although distinct phases of LTM already have been demonstrated in some systems, it is not known whether these phases require distinct temporal patterns of learning-induced PKA activation. This question was addressed in a robust form of associative LTM that emerges within a matter of hours after single-trial food-reward classical conditioning in the pond snail Lymnaea stagnalis. After establishing the molecular and functional identity of the PKA catalytic subunit in the Lymnaea nervous system, we used a combination of PKA activity measurement and inhibition techniques to investigate its role in LTM in intact animals. PKA activity in ganglia involved in single-trial learning showed a short latency but prolonged increase after classical conditioning. However, while increased PKA activity immediately after training (0-10 min) was essential for an early phase of LTM (6 h), the late phase of LTM (24 h) required a prolonged increase in PKA activity. These observations indicate mechanistically different roles for PKA in recent and more remote phases of LTM, which may underpin different cellular and molecular mechanisms required for these phases.