Calcium/calmodulin-dependent kinase IV contributes to translation-dependent early synaptic potentiation in the anterior cingulate cortex of adult mice.
Calcium/calmodulin-dependent kinase IV contributes to translation-dependent early synaptic potentiation in the anterior cingulate cortex of adult mice.
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DOI：
10.1186/1756-6606-3-27
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发表时间：
2010-09-16
期刊：
影响因子：
3.6
通讯作者：
Zhuo M
中科院分区：
文献类型：
--
作者：
Toyoda H;Zhao MG;Mercaldo V;Chen T;Descalzi G;Kida S;Zhuo M
钙/钙调蛋白依赖性激酶IV（CaMKIV）磷酸化主要转录因子环腺苷酸反应元件结合蛋白（CREB），其在突触可塑性和记忆巩固中起关键作用。我们以前的研究表明，长时程增强（LTP）在前扣带皮层（ACC）显着增强过表达CaMKIV的转基因小鼠。考虑到CaMKIV-CREB通路在蛋白质合成依赖性LTP中起着核心作用，CaMKIV的上调可能通过促进蛋白质合成而有助于增强LTP。为了测试这种可能性，我们研究了转录和翻译抑制剂对野生型和CaMKIV转基因小鼠ACC锥体神经元中突触活动与突触后去极化（配对训练）配对诱导的突触增强的影响。我们发现，配对训练诱导的突触增强部分抑制转录或翻译抑制剂在野生型和CaMKIV转基因小鼠的抑制程度明显大于在野生型小鼠的CaMKIV转基因小鼠。生化和免疫组织化学研究表明，CaMKIV分布在ACC神经元的膜，胞浆和细胞核。我们的结果首次揭示了成人ACC突触早期突触LTP的转录和翻译依赖性成分，并证明CaMKIV通过激活新蛋白质合成来增强早期突触增强作用。
Calcium/calmodulin-dependent kinase IV (CaMKIV) phosphorylates the major transcription factor, cyclic AMP-responsive element binding protein (CREB), which plays key roles in synaptic plasticity and memory consolidation. Our previous study showed that long-term potentiation (LTP) in the anterior cingulate cortex (ACC) was significantly enhanced in transgenic mice overexpressing CaMKIV. Considering that the CaMKIV-CREB pathway plays a central role in the protein synthesis-dependent LTP, it is possible that upregulation of CaMKIV contributes to enhancement of LTP by promoting protein synthesis. To test this possibility, we examined the effects of transcription and translation inhibitors on synaptic potentiation induced by pairing of synaptic activity with postsynaptic depolarization (paired training) in ACC pyramidal neurons of wild-type and CaMKIV transgenic mice. We found that synaptic potentiation induced by paired training was partially inhibited by transcription or translation inhibitors both in wild-type and CaMKIV transgenic mice; the extent of inhibition was markedly larger in the CaMKIV transgenic mice than in the wild-type mice. Biochemical and immunohistochemical studies revealed that CaMKIV was distributed in the membrane, cytosol and nucleus of ACC neurons. Our results reveal in the first time a transcription- and translation-dependent component of early synaptic LTP in adult ACC synapses, and demonstrate that CaMKIV enhances early synaptic potentiation by activating new protein synthesis.
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影响因子：
56.9
作者：
Frankland, PW;Bontempi, B;Silva, AJ
通讯作者：
Silva, AJ
影响因子：
25
作者：
Kida, S;Josselyn, SA;Silva, AJ
通讯作者：
Silva, AJ
影响因子：
3.8
作者：
KRUG, M;LOSSNER, B;OTT, T
通讯作者：
OTT, T
DOI：
10.1073/pnas.0308280101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Huang, YY;Simpson, E;Kandel, ER
通讯作者：
Kandel, ER
影响因子：
64.5
作者：
HUANG, YY;LI, XC;KANDEL, ER
通讯作者：
KANDEL, ER