Brief Theta-burst stimulation induces a transcription-dependent late phase of LTP requiring cAMP in area CA1 of the mouse hippocampus
Brief Theta-burst stimulation induces a transcription-dependent late phase of LTP requiring cAMP in area CA1 of the mouse hippocampus
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DOI：
10.1101/lm.4.2.230
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发表时间：
1997-07-01
影响因子：
2
通讯作者：
Kandel, ER
中科院分区：
文献类型：
--
作者：
Nguyen, PV;Kandel, ER
哺乳动物大脑中的记忆存储可以分为独立于新蛋白质合成的短期阶段和需要新RNA和蛋白质合成的长期阶段。这两个阶段的细胞模型已经从海马中三个主要兴奋性突触通路中的长时程增强（LTP）的研究中出现，一个特别有效的方案，诱导强大的和持久的LTP是“θ-突发”刺激，这是为了模仿海马神经元的放电模式记录在探索行为在完整的清醒动物。与非Theta破伤风方案诱导的LTP不同，对海马中Theta爆发LTP的生化机制知之甚少。在本研究中，我们检测了Schaffer侧支通路中的Theta爆发LTP。我们发现，3秒的Theta爆发刺激诱导小鼠海马脑片中的一个强大的和持久的增强（Theta L-LTP）。这种Theta L-LTP依赖于NMDA受体的激活。Theta-LTP的初始或早期阶段不需要蛋白质或RNA合成，并且不依赖于cAMP依赖性蛋白激酶（PKA）激活。相反，Theta-LTP的晚期需要蛋白质和RNA的合成，并被PKA抑制剂阻断。我们的研究结果表明，像non-Theta LTP，Theta诱导的LTP在小鼠海马CA 1区也涉及转录，翻译和PKA，并建议cAMP介导的基因转录可能是一个共同的机制，负责由Theta和non-Theta模式的刺激诱导的LTP的晚期阶段。
Memory storage in the mammalian brain can be divided into a short-term phase that is independent of new protein synthesis and a long-term phase that requires synthesis of new RNA and proteins, A cellular model for these two phases has emerged from studies of long-term potentiation (LTP) in the three major excitatory synaptic pathways in the hippocampus, One especially effective protocol for inducing robust and persistent LTP is ''Theta-burst'' stimulation, which is designed to mimic the firing patterns of hippocampal neurons recorded during exploratory behavior in intact awake animals. Unlike LTP induced by non-Theta tetanization regimens, little is known about the biochemical mechanisms underlying Theta-burst LTP in the hippocampus. in the present study, we examined Theta-burst LTP in the Schaffer collateral pathway. We found that 3 sec of Theta-burst stimulation induced a robust and persistent potentiation (Theta L-LTP) in mouse hippocampal slices. This Theta L-LTP was dependent on NMDA receptor activation. The initial or early phase of Theta-LTP did not require either protein or RNA synthesis and was independent of cAMP-dependent protein kinase (PKA) activation. in contrast, the late phase of Theta-LTP required synthesis of proteins and RNA and was blocked by inhibitors of PKA.Prior induction of Theta-LTP also occluded the potentiation elicited by chemical activation of PKA. Our results show that, Like non-Theta LTP, Theta-induced LTP in area CA1 of the mouse hippocampus also involves transcription, translation, and PKA and suggest that cAMP-mediated gene transcription may be a common mechanism responsible for the late phases of LTP induced by both Theta and non-Theta patterns of stimulation.