Kampa Björn M, Stuart Greg J
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
J Neurosci. 2006 Jul 12;26(28):7424-32. doi: 10.1523/JNEUROSCI.3062-05.2006.
Patch-clamp recording from dendrites has lead to a significant increase in our understanding of the mechanisms underlying signal integration and propagation in neurons. The majority of synaptic input to neurons, however, is made onto small-diameter dendrites, currently beyond the scope of patch-clamp recording techniques. Here we use both calcium and voltage imaging to investigate propagation of action potentials (APs) in fine basal dendrites of cortical layer 5 pyramidal neurons. High-frequency (200 Hz) AP bursts caused supralinear increases in dendritic calcium at distal, but not proximal, basal locations. Supralinear increases in dendritic calcium were also observed at distal basal locations during AP trains above a critical frequency (approximately 100 Hz). Using voltage imaging, we show that single APs undergo significant attenuation as they propagate into basal dendrites, whereas AP bursts lead to generation of dendritic calcium spikes. Focal and bath application of 4-AP increased the amplitude of calcium transients evoked by APs at distal, but not proximal, locations, suggesting that A-type potassium channels regulate AP backpropagation into basal dendrites. Finally, we show that pairing EPSPs with AP bursts is an effective means of activating synaptic NMDA receptors in basal dendrites. The experimental observations on the role of A-type potassium channels in regulation of AP backpropagation in basal dendrites, as well as the generation of dendritic calcium spikes during AP bursts, were reproduced in a morphologically realistic neuronal model with uniform distributions of dendritic sodium, calcium, and potassium channels. Together, these findings have important implications for understanding dendritic integration and synaptic plasticity in cortical basal dendrites.
对树突进行膜片钳记录极大地增进了我们对神经元信号整合与传播机制的理解。然而，神经元的大多数突触输入是作用于小直径树突上的，目前这超出了膜片钳记录技术的范围。在此，我们利用钙成像和电压成像来研究皮层第5层锥体神经元细基树突中动作电位（AP）的传播。高频（200赫兹）AP爆发在远端而非近端基树突位置引起树突钙的超线性增加。在高于临界频率（约100赫兹）的AP串期间，在远端基树突位置也观察到树突钙的超线性增加。利用电压成像，我们发现单个AP在向基树突传播时会经历显著衰减，而AP爆发会导致树突钙峰的产生。局部和浴式应用4-氨基吡啶增加了AP在远端而非近端位置诱发的钙瞬变幅度，表明A 型钾通道调节AP向基树突的反向传播。最后，我们表明将兴奋性突触后电位（EPSP）与AP爆发配对是激活基树突中突触N-甲基-D-天冬氨酸（NMDA）受体的有效手段。在一个具有树突钠、钙和钾通道均匀分布的形态逼真的神经元模型中，再现了关于A 型钾通道在调节AP向基树突反向传播中的作用以及AP爆发期间树突钙峰产生的实验观察结果。总之，这些发现对于理解皮层基树突中的树突整合和突触可塑性具有重要意义。
