Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice.
Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice.
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DOI：
10.1016/j.nlm.2012.10.003
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发表时间：
2013-01
影响因子：
2.7
通讯作者：
Ziff, Edward B.
中科院分区：
文献类型：
--
作者：
Wincott, Charlotte M.;Kim, Seonil;Titcombe, Roseann F.;Tukey, David S.;Girma, Hiwot K.;Pick, Joseph E.;DeVito, Loren M.;Hofmann, Franz;Hoeffer, Charles;Ziff, Edward B.
AMPA受体向突触的活性依赖运输调节突触的强度。NMDA受体的激活诱导了几个第二信使通路，这些信使通路有助于受体转运依赖的可塑性，其中包括NO通路，它提高了cGMP。反过来，cGMP激活cGMP依赖的蛋白激酶II(CGKII)，使AMPA受体亚基GluA1在丝氨酸845处磷酸化，这是在活性依赖性突触增强机制中促进突触传递的关键步骤。由于cGKII在纹状体、杏仁核、大脑皮层和海马区都有表达，因此有人认为，与野生型相比，缺乏cGKII的小鼠在情感依赖任务、学习和记忆以及药物奖励显著方面可能表现出不同的表型。先前的研究表明，与野生型(WT)小鼠相比，cGKII KO小鼠摄入更多的乙醇，并表现出更高的焦虑水平。在这里，我们显示了cGKII KO小鼠在空间学习方面的显著缺陷，同时表现出促进运动协调，表明基于记忆的任务对cGKII具有明显的依赖性。我们还发现cGKII KO前额叶皮质突触后密度(PSD)中的GluA1磷酸化水平降低，而在海马PSD部分中，GluA1磷酸化水平没有明显变化。这些数据表明，cGKII的作用在特定的大脑区域可能更强大，从而以不同的方式影响依赖于这些区域的复杂行为。
Activity-dependent trafficking of AMPA receptors to synapses regulates synaptic strength. Activation of the NMDA receptor induces several second messenger pathways that contribute to receptor trafficking-dependent plasticity, including the NO pathway, which elevates cGMP. In turn, cGMP activates the cGMP-dependent protein kinase type II (cGKII), which phosphorylates the AMPA receptor subunit GluA1 at serine 845, a critical step facilitating synaptic delivery in the mechanism of activity-dependent synaptic potentiation. Since cGKII is expressed in the striatum, amygdala, cerebral cortex, and hippocampus, it has been proposed that mice lacking cGKII may present phenotypic differences compared to their wild-type littermates in emotion-dependent tasks, learning and memory, and drug reward salience. Previous studies have shown that cGKII KO mice ingest higher amounts of ethanol as well as exhibit elevated anxiety levels compared to wild-type (WT) littermates. Here, we show that cGKII KO mice are significantly deficient in spatial learning while exhibiting facilitated motor coordination, demonstrating a clear dependence of memory-based tasks on cGKII. We also show diminished GluA1 phosphorylation in the postsynaptic density (PSD) of cGKII KO prefrontal cortex while in hippocampal PSD fractions, phosphorylation was not significantly altered. These data suggest that the role of cGKII may be more robust in particular brain regions, thereby impacting complex behaviors dependent on these regions differently.
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影响因子：
4.3
作者：
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通讯作者：
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