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      Site of Action Potential Initiation in Layer 5 Pyramidal Neurons

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          Abstract

          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 ∼35 μm 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 μm 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 ∼40 μm in length, and the first node of Ranvier was ∼90 μm 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.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          8 February 2006
          : 26
          : 6
          : 1854-1863
          Affiliations
          Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 0200, Australia
          Author notes
          Correspondence should be addressed to Greg J. Stuart at the above address. Email: greg.stuart@ 123456anu.edu.au
          Article
          PMC6793621 PMC6793621 6793621 zns1854
          10.1523/JNEUROSCI.4812-05.2006
          6793621
          16467534
          Copyright © 2006 Society for Neuroscience 0270-6474/06/261854-10$15.00/0
          Categories
          Articles
          Cellular/Molecular
          Custom metadata
          1854
          research-article

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