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首页> 外文期刊>The European Journal of Neuroscience >Differential effects of alphaCaMKII mutation on hippocampal learning and changes in intrinsic neuronal excitability.
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Differential effects of alphaCaMKII mutation on hippocampal learning and changes in intrinsic neuronal excitability.

机译：alphaCaMKII突变对海马学习和内在神经元兴奋性变化的差异影响。

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Alpha-calcium/calmodulin-dependent kinase II (alphaCaMKII) is central to synaptic plasticity but it remains unclear whether this kinase contributes to neuronal excitability changes, which are a cellular correlate of learning. Using knock-in mice with a targeted T286A mutation that prevents the autophosphorylation of alphaCaMKII (alphaCaMKII(T286A)), we studied the role of alphaCaMKII signaling in regulating hippocampal neuronal excitability during hippocampus-dependent spatial learning in the Morris water maze. Wild-type control mice showed increased excitability of CA1 pyramidal neurons, as assessed by a reduction in the postburst afterhyperpolarization (AHP), after spatial training in the water maze. Importantly, wild-type mice did not show AHP changes when they were exposed to the water maze without the escape platform and swam the same amount of time as the trained mice (swim controls), thus manifesting learning-specific increases in hippocampal CA1 excitability associated with spatial training. Meanwhile, alphaCaMKII(T286A) mice showed impairments in spatial learning but exhibited reduced levels of AHP that were similar to wild-type controls after water-maze training. Notably, both trained and swim-control groups of alphaCaMKII(T286A) mutants showed similar increased excitability, indicating that swimming by itself is enough to induce changes in excitability in the absence of normal alphaCaMKII function. This result demonstrates dissociation of alphaCaMKII-independent changes in intrinsic neuron excitability from learning and synaptic plasticity mechanisms, suggesting that increases in excitability per se are not perfectly correlated with learning. Our findings suggest that alphaCaMKII signaling may function to suppress learning-unrelated changes during training, thereby allowing hippocampal CA1 neurons to increase their excitability appropriately for encoding spatial memories.
机译：α-钙/钙调蛋白依赖性激酶II（alphaCaMKII）是突触可塑性的核心，但尚不清楚该激酶是否有助于神经元兴奋性变化，这是学习的细胞相关因素。使用具有靶向性T286A突变的敲除小鼠来预防alphaCaMKII（alphaCaMKII（T286A）的自磷酸化），我们研究了在Morris水迷宫中依赖海马的空间学习过程中alphaCaMKII信号在调节海马神经元兴奋性中的作用。通过在水迷宫中进行空间训练后爆发后的超极化（AHP）减少来评估，野生型对照小鼠的CA1锥体神经元兴奋性增强。重要的是，野生型小鼠在没有逃生平台的情况下暴露于水迷宫中并游走的时间与训练有素的小鼠（游泳对照组）的时间相同，因此没有显示AHP的变化，因此表明与学习相关的海马CA1兴奋性增加与空间训练。同时，alphaCaMKII（T286A）小鼠表现出空间学习障碍，但在水迷宫训练后表现出的AHP降低水平与野生型对照相似。值得注意的是，训练有素的和游泳对照组的αCaMKII（T286A）突变体都显示出相似的兴奋性增加，表明在没有正常alphaCaMKII功能的情况下，游泳本身足以引起兴奋性变化。该结果表明，与学习和突触可塑性机制无关的内在神经元兴奋性中独立于alphaCaMKII的变化已经解离，这表明兴奋性本身的提高与学习并不完全相关。我们的发现表明，αCaMKII信号传导可能会抑制训练过程中与学习无关的变化，从而使海马CA1神经元能够适当增加其兴奋性以编码空间记忆。

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