Rosenkranz J Amiel, Frick Andreas, Johnston Daniel
Center for Learning and Memory, University of Texas at Austin, Austin, TX, USA.
J Physiol. 2009 Jan 15;587(1):115-25. doi: 10.1113/jphysiol.2008.158816. Epub 2008 Nov 10.
Patterns of presynaptic activity properly timed with postsynaptic action potential output can not only increase the strength of synaptic inputs but can also increase the excitability of dendritic branches of adult CA1 pyramidal neurons. Here, we examined the role of protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) in the enhancement of dendritic excitability that occurs during theta-burst pairing of presynaptic and postsynaptic firing activity. Using dendritic and somatic whole-cell recordings in rat hippocampal slices, we measured the increase in the amplitude of back-propagating action potentials in the apical dendrite that occurs in parallel with long-term potentiation (LTP) of synaptic inputs. We found that inhibition of the MAPK pathway prevents this enhancement of dendritic excitability using either a weak or strong LTP induction protocol, while synaptic LTP can still be induced by the strong protocol. Both forms of plasticity are blocked by inhibition of PKA and occluded by interfering with cAMP degradation, consistent with a PKA-mediated increase in MAPK activity following induction of LTP. This provides a signalling mechanism for plasticity of dendritic excitability that occurs during neuronal activity and demonstrates the necessity of MAPK activation. Furthermore, this study uncovers an additional contribution of kinase activation to plasticity that may occur during learning.
与突触后动作电位输出精确同步的突触前活动模式，不仅可以增强突触输入的强度，还可以提高成年CA1锥体神经元树突分支的兴奋性。在这里，我们研究了蛋白激酶A（PKA）和丝裂原活化蛋白激酶（MAPK）在突触前和突触后放电活动的θ波爆发配对过程中，增强树突兴奋性所起的作用。利用大鼠海马切片中的树突和体细胞全细胞记录，我们测量了与突触输入的长期增强（LTP）同时发生的顶树突中反向传播动作电位幅度的增加。我们发现，无论是使用弱LTP诱导方案还是强LTP诱导方案，抑制MAPK途径都会阻止树突兴奋性的这种增强，而强方案仍可诱导突触LTP。两种形式的可塑性都被PKA抑制所阻断，并被干扰cAMP降解所掩盖，这与LTP诱导后PKA介导的MAPK活性增加一致。这为神经元活动期间发生的树突兴奋性可塑性提供了一种信号机制，并证明了MAPK激活的必要性。此外，这项研究揭示了激酶激活对学习过程中可能发生的可塑性的额外贡献。
