Learning-related postburst afterhyperpolarization reduction in CA1 pyramidal neurons is mediated by protein kinase A
Learning-related postburst afterhyperpolarization reduction in CA1 pyramidal neurons is mediated by protein kinase A
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DOI：
10.1073/pnas.0807708106
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发表时间：
2009-02-03
影响因子：
11.1
通讯作者：
Disterhoft, John F.
中科院分区：
文献类型：
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作者：
Oh, M. Matthew;McKay, Bridget M.;Disterhoft, John F.
海马区锥体神经元爆发式后超极化(AHP)的学习相关的减少已显示在体外，在示踪眨眼条件下。许多神经调节剂，如去甲肾上腺素，也通过激活蛋白激酶来降低AHP。就像其他依赖海马体的任务一样，痕迹眨眼条件反射依赖于蛋白质合成来巩固学习记忆。蛋白激酶A(PKA)通过cAMP反应元件结合途径对蛋白质合成起关键作用。在这里，我们探索了PKA和蛋白激酶C(PKC)在维持CA1锥体神经元中观察到的与学习相关的爆发性AHP降低中的潜在参与。沐浴应用异丙肾上腺素(1MU M)，一种能激活PKA的β-肾上腺素能激动剂，显著降低对照组动物CA1神经元的AHP，但对学习大鼠则没有。这一阻断表明，PKA活性参与了成功学习后维持体外测量的AHP降低的过程。相反，应用PKC激动剂(-)吲哚内酰胺V(0.2mM)可显著降低对照组和训练大鼠CA1区神经元的AHP，表明PKC活性不参与维持学习后此时AHP的降低。
Learning-related reductions of the postburst afterhyperpolarization (AHP) in hippocampal pyramidal neurons have been shown ex vivo, after trace eyeblink conditioning. The AHP is also reduced by many neuromodulators, such as norepinephrine, via activation of protein kinases. Trace eyeblink conditioning, like other hippocampus-dependent tasks, relies on protein synthesis for consolidating the learned memory. Protein kinase A (PKA) has been shown to be a key contributor for protein synthesis via the cAMP-response element-binding pathway. Here, we have explored a potential involvement of PKA and protein kinase C (PKC) in maintaining the learning-related postburst AHP reduction observed in CA1 pyramidal neurons. Bath application of isoproterenol (1 mu M), a beta-adrenergic agonist that activates PKA, significantly reduced the AHP in CA1 neurons from control animals, but not from rats that learned. This occlusion suggests that PKA activity is involved in maintaining the AHP reduction measured ex vivo after successful learning. In contrast, bath application of the PKC activator, (-) indolactam V (0.2 mu M), significantly reduced the AHP in CA1 neurons from both control and trained rats, indicating that PKC activity is not involved in maintaining the AHP reduction at this point after learning.