Palmer Lucy M, Stuart Greg J
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 0200, Australia.
J Neurosci. 2006 Feb 8;26(6):1854-63. doi: 10.1523/JNEUROSCI.4812-05.2006.
Fundamental to an understanding of how neurons integrate synaptic input is the knowledge of where within a neuron this information is converted into an output signal, the action potential. Although it has been known for some time that action potential initiation occurs within the axon of neurons, the precise location has remained elusive. Here, we provide direct evidence using voltage-sensitive dyes that the site of action potential initiation in cortical layer 5 pyramidal neurons is approximately 35 microm from the axon hillock. This was the case during action potential generation under a variety of conditions, after axonal inhibition, and at different stages of development. Once initiated action potentials propagated down the axon in a saltatory manner. Experiments using local application of low-sodium solution and TTX, as well as an investigation of the influence of axonal length on action potential properties, provided evidence that the initial 40 microm of the axon is essential for action potential generation. To morphologically identify the relationship between the site of action potential initiation and axonal myelination, we labeled oligodendrocytes supplying processes to the proximal region of the axon. These experiments indicated that the axon initial segment was approximately 40 mcirom in length, and the first node of Ranvier was approximately 90 microm from the axon hillock. Experiments targeting the first node of Ranvier suggested it was not involved in action potential initiation. In conclusion, these results indicate that, in layer 5 pyramidal neurons, action potentials are generated in the distal region of the axon initial segment.
理解神经元如何整合突触输入的基础是了解在神经元的哪个部位该信息被转换为输出信号,即动作电位。尽管人们早就知道动作电位起始于神经元的轴突内,但确切位置一直难以确定。在这里,我们使用电压敏感染料提供了直接证据,表明皮层第5层锥体神经元的动作电位起始位点距离轴丘约35微米。在各种条件下的动作电位产生过程中、轴突抑制后以及不同发育阶段都是如此。一旦动作电位起始,就会以跳跃的方式沿轴突向下传播。使用局部应用低钠溶液和河豚毒素的实验,以及对轴突长度对动作电位特性影响的研究,提供了证据表明轴突的最初40微米对于动作电位的产生至关重要。为了从形态学上确定动作电位起始位点与轴突髓鞘形成之间的关系,我们标记了向轴突近端区域提供突起的少突胶质细胞。这些实验表明轴突起始段长度约为40微米,郎飞氏结的第一个结距离轴丘约90微米。针对郎飞氏结第一个结的实验表明它不参与动作电位的起始。总之,这些结果表明,在第5层锥体神经元中,动作电位在轴突起始段的远端区域产生。