Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus
Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus
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DOI：
10.1016/s0896-6273(00)80120-8
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发表时间：
1996-05-01
期刊：
影响因子：
16.2
通讯作者：
Storm, DR
中科院分区：
文献类型：
--
作者：
Impey, S;Mark, M;Storm, DR
cAMP反应元件（CRE）调控的基因表达与突触可塑性和长期记忆有关。已经提出，CRE介导的基因表达由诱导长时程增强（LTP）的信号刺激。为了验证这一假设，我们制作了CRE调控的报告基因转基因小鼠。我们重点关注持久的长时程增强（L-LTP），因为它取决于cAMP依赖性蛋白激酶活性（PKA）和从头基因表达。CRE介导的基因表达在L-LTP后显著增加，但在递减LTP（D-LTP）后没有增加。此外，PKA抑制剂阻断L-LTP和相关的CREE介导的基因表达增加。这些数据表明，产生L-LTP而不是D-LTP所需的信号传导足以刺激海马中的CRE介导的转录。
Gene expression regulated by the cAMP response element (CRE) has been implicated in synaptic plasticity and long-term memory. It has been proposed that CRE-mediated gene expression is stimulated by signals that induce long-term potentiation (LTP). To test this hypothesis, we made mice transgenic for a CRE-regulated reporter construct. We focused on longlasting long-term potentiation (L-LTP), because it depends on cAMP-dependent protein kinase activity (PKA) and de novo gene expression. CRE-mediated gene expression was markedly increased after L-LTP, but not after decremental LTP (D-LTP). Furthermore, inhibitors of PKA blocked L-LTP and associated increases in CRE-mediated gene expression. These data demonstrate that the signaling required for the generation of L-LTP but not D-LTP is sufficient to stimulate CRE-mediated transcription in the hippocampus.