Differential involvement of hippocampal calcineurin during learning and reversal learning in a Y-maze task
Differential involvement of hippocampal calcineurin during learning and reversal learning in a Y-maze task
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DOI：
10.1101/lm.323606
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发表时间：
2006-11-01
影响因子：
2
通讯作者：
Van der Zee, Eddy A.
中科院分区：
文献类型：
--
作者：
Havekes, Robbert;Nijholt, Ingrid M.;Van der Zee, Eddy A.
钙依赖性磷酸酶钙调神经磷酸酶（CaN，蛋白磷酸酶2B）在学习和记忆中的调节和功能尚不清楚，尽管最近的工作表明，CaN可能在训练和逆转训练中发挥不同的作用。为了更深入地了解钙调神经参与这两种类型的学习，海马钙调神经活性，蛋白水平和表达模式进行了研究，在小鼠的参考记忆版本的Y-迷宫任务。我们发现：（1）训练而非习惯化诱导胞浆CaN活性降低，（2）胞浆CaN活性的恢复是逆转训练特异性的，并不反映与后续学习无关的基础水平的正常恢复，（3）CaN催化亚基（CaNA）的胞浆蛋白水平在训练早期降低，但在逆转训练早期不降低，（4）背侧海马CA 1和CA 3区CaNA免疫反应性仅在反向训练时增强，而齿状回（DG）和下托（海马下托）则无明显变化。这些发现表明，记忆的形成伴随着CaN活性的降低，而适应熟悉环境中的变化则伴随着CaN活性的恢复。此外，逆转训练选择性地影响海马CA 3和CA 1区，这表明这些海马亚区在逆转学习中的特定功能。
The regulation and function of the calcium-dependent phosphatase calcineurin (CaN, protein phosphatase 2B) in learning and memory remain unclear, although recent work indicates that CaN may play a differential role in training and reversal training. To gain more insight into the involvement of CaN in these two types of learning, hippocampal CaN activity, protein levels, and expression patterns were studied in mice subjected to a reference memory version of the Y-maze task. We show that (1) training but not habituation induces a decrease in cytosolic CaN activity, (2) the recovery of cytosolic CaN activity is reversal training specific and does not reflect normal restoration of basal levels unrelated to subsequent learning, (3) cytosolic protein levels for the catalytic subunit of CaN (CaNA) are decreased at the early phase of training, but not at the early phase of reversal training, (4) CaNA immunoreactivity in the dorsal hippocampus is enhanced in the CA1 and CA3 area (but not in the dentate gyrus [DG] or subiculum [SUB]) only during reversal training. These findings indicate that memory formation is accompanied by reduced CaN activity, whereas adapting to changes in a familiar environment is accompanied by restored CaN activity. Moreover, reversal training selectively affects hippocampal CA3 and CA1 regions, suggesting a specific function of these hippocampal subregions in reversal learning.