cGMP-dependent protein kinase Type I promotes CREB/CRE-mediated gene expression in neurons of the lateral amygdala
cGMP-dependent protein kinase Type I promotes CREB/CRE-mediated gene expression in neurons of the lateral amygdala
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DOI：
10.1016/j.neulet.2010.02.020
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发表时间：
2010-04-05
影响因子：
2.5
通讯作者：
Kleppisch, Thomas
中科院分区：
文献类型：
--
作者：
Paul, Cindy;Stratil, Christopher;Kleppisch, Thomas
将新学到的信息转化为稳定的长期记忆的过程称为记忆巩固，就像潜在的长期突触可塑性一样，关键取决于从头RNA和蛋白质的合成。我们最近发现cGMP依赖性蛋白激酶I（cGKI）在杏仁核依赖性恐惧记忆的巩固和外侧杏仁核的长时程增强（LTP）中起重要作用。在转录调控水平上cGKI下游的信号传导仍不清楚。cAMP反应元件结合蛋白（CREB）是一种对学习和记忆非常重要的转录因子。外侧杏仁核中恐惧记忆的表征显著依赖于单个神经元中CREB的活性。此外，来自体外实验的发现证明CREB被cGK磷酸化。在海马中，CREB磷酸化在NO/cGMP信号传导激活后增加，导致LTP的晚期。为了证明从cGKI激活CREB和CREB依赖性转录的外侧杏仁核的神经元作为一个可能的机制cGKI介导的恐惧记忆巩固的链接，我们研究了cGMP激活CREB/CRE的影响，使用磷酸化CREB特异性免疫组织化学染色和报告基因在控制和cGKI缺陷小鼠，分别。支持我们的假设，显着的CREB磷酸化和CRE介导的转录诱导cGMP在侧杏仁核的对照组小鼠，但不是在CGKI缺陷小鼠。已经提出cGKI的活化之后是其核易位，这将允许CREB的直接磷酸化。因此，我们检查了细胞定位的cGKI在侧杏仁核的神经元cGMP的存在下，通过双重染色的cGKI和核标记物的部分显示出显着的CREB磷酸化，并没有观察到显着的核转位的酶。总之，我们提供的证据表明，胞质cGKI可以支持恐惧记忆巩固和LTP的外侧杏仁核神经元通过激活CREB和CRE-dependent转录。(C)2010爱思唯尔爱尔兰有限公司版权所有。
The process transforming newly learned information into stable long-term memory is called memory consolidation and, like the underlying long-term synaptic plasticity, critically depends on de novo RNA and protein synthesis. We have shown recently that the cGMP-dependent protein kinase Type I (cGKI) plays an important role for the consolidation of amygdala-dependent fear memory and long-term potentiation (LTP) in the lateral amygdala. Signalling downstream of cGKI at the level of transcriptional regulation remained unclear. A transcription factor of major importance for learning and memory is the cAMP-response element binding protein (CREB). The representation of fear memory in the lateral amygdala strikingly depends on the activity of CREB in individual neurons. Moreover, findings from in vitro experiments demonstrate CREB phosphorylation by cGK. In the hippocampus, CREB phosphorylation increases following activation of NO/cGMP signalling contributing to the late phase of LTP. To demonstrate a link from cGKI to activation of CREB and CREB-dependent transcription in neurons of the lateral amygdala as a possible mechanism for cGKI-mediated fear memory consolidation, we examined the effect of cGMP on activation of CREB/CRE using immunohistochemical staining specific for phospho-CREB and a reporter gene in control and cGKI-deficient mice, respectively. Supporting our hypothesis, marked CREB phosphorylation and CRE-mediated transcription was induced by cGMP in the lateral amygdala of control mice, but not in cGKI-deficient mice. It has been proposed that activation of cGKI is followed by its nuclear translocation that would allow direct phosphorylation of CREB. Therefore, we examined the cellular localisation of cGKI in neurons of the lateral amygdala in the presence of cGMP by double staining for cGKI and a nuclear marker in sections from areas showing prominent CREB phosphorylation, and did not observe prominent nuclear translocation of the enzyme. In summary, we provide evidence that cytosolic cGKI can support fear memory consolidation and LTP in neurons of the lateral amygdala via activation of CREB and CRE-dependent transcription. (C) 2010 Elsevier Ireland Ltd. All rights reserved.