Oh M Matthew, McKay Bridget M, Power John M, Disterhoft John F
Department of Physiology and Neuroscience Program, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611-3008, USA.
Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1620-5. doi: 10.1073/pnas.0807708106. Epub 2009 Jan 21.
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 muM), 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 muM), 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.
在海马体锥体神经元中，与学习相关的爆发后超极化（AHP）减少已在离体条件下，经痕迹性眨眼条件反射后得到证实。许多神经调质，如去甲肾上腺素，通过激活蛋白激酶也可使AHP降低。与其他依赖海马体的任务一样，痕迹性眨眼条件反射依赖蛋白质合成来巩固所学记忆。蛋白激酶A（PKA）已被证明是通过环磷酸腺苷反应元件结合途径参与蛋白质合成的关键因素。在此，我们探究了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后AHP降低方面的潜在作用。浴槽给药异丙肾上腺素（1μM），一种激活PKA的β-肾上腺素能激动剂，可显著降低对照动物CA1神经元中的AHP，但对已学习的大鼠无效。这种阻断现象表明，PKA活性参与维持成功学习后离体测量的AHP降低。相比之下，浴槽给药PKC激活剂（-）吲哚拉明V（0.2μM）可显著降低对照大鼠和训练大鼠CA1神经元中的AHP，这表明PKC活性在此时不参与维持学习后AHP的降低。
