Genetic inhibition of CaMKII in dorsal striatal medium spiny neurons reduces functional excitatory synapses and enhances intrinsic excitability.
Genetic inhibition of CaMKII in dorsal striatal medium spiny neurons reduces functional excitatory synapses and enhances intrinsic excitability.
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DOI：
10.1371/journal.pone.0045323
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Winder DG
中科院分区：
文献类型：
--
作者：
Klug JR;Mathur BN;Kash TL;Wang HD;Matthews RT;Robison AJ;Anderson ME;Deutch AY;Lovinger DM;Colbran RJ;Winder DG
Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）在纹状体中型棘神经元（MSNs）中含量丰富。CaMKII受多巴胺信号传导变化的动态调节，如帕金森病和成瘾中所发生的那样。虽然CaMKII在海马中调节兴奋性突触传递已被广泛研究，但关于其如何调节纹状体中的神经元功能的了解相对较少。因此，我们使用一种新的转基因小鼠模型，研究了选择性过表达融合EGFP的CaMKII抑制肽（EAC 3 I）在纹状体中棘神经元（MSN）中的影响。表达EAC 3 I的细胞表现出明显降低的兴奋性传递，表明自发兴奋性突触后电流（sEPSC）的频率降低。这种减少并不伴随着释放概率的变化、突触处谷氨酸水平的变化或树突棘密度的变化。AMPA受体亚基GluA 1的CaMK II调节是激酶调节海马神经元功能的主要手段。我们发现在EAC 3 I小鼠中看到的纹状体兴奋性传递的减少是通过GluA 1的缺失来模仿的。此外，虽然CaMKII抑制减少了对MSN的兴奋性传递，但增加了其内在的兴奋性。这些数据表明，CaMKII通过协调兴奋性突触驱动和由此产生的去极化反应在设置纹状体MSNs的兴奋性变阻器中起着关键作用。
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is abundant in striatal medium spiny neurons (MSNs). CaMKII is dynamically regulated by changes in dopamine signaling, as occurs in Parkinson's disease as well as addiction. Although CaMKII has been extensively studied in the hippocampus where it regulates excitatory synaptic transmission, relatively little is known about how it modulates neuronal function in the striatum. Therefore, we examined the impact of selectively overexpressing an EGFP-fused CaMKII inhibitory peptide (EAC3I) in striatal medium spiny neurons (MSNs) using a novel transgenic mouse model. EAC3I-expressing cells exhibited markedly decreased excitatory transmission, indicated by a decrease in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). This decrease was not accompanied by changes in the probability of release, levels of glutamate at the synapse, or changes in dendritic spine density. CaMKII regulation of the AMPA receptor subunit GluA1 is a major means by which the kinase regulates neuronal function in the hippocampus. We found that the decrease in striatal excitatory transmission seen in the EAC3I mice is mimicked by deletion of GluA1. Further, while CaMKII inhibition decreased excitatory transmission onto MSNs, it increased their intrinsic excitability. These data suggest that CaMKII plays a critical role in setting the excitability rheostat of striatal MSNs by coordinating excitatory synaptic drive and the resulting depolarization response.
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影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
DOI：
10.1006/bbrc.2000.3145
发表时间：
2000-08-02
影响因子：
3.1
作者：
Carlier, E;Dargent, B;Couraud, F
通讯作者：
Couraud, F
影响因子：
64.8
作者：
Benke, TA;Lüthi, A;Collingridge, GL
通讯作者：
Collingridge, GL
影响因子：
3.7
作者：
Baucum, Anthony J., II;Strack, Stefan;Colbran, Roger J.
通讯作者：
Colbran, Roger J.
影响因子：
64.8
作者：
Durand, GM;Kovalchuk, Y;Konnerth, A
通讯作者：
Konnerth, A