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The Journal of Neuroscience, February 8, 2006, 26(6):1854-1863; doi:10.1523/JNEUROSCI.4812-05.2006
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Cellular/Molecular
Site of Action Potential Initiation in Layer 5 Pyramidal Neurons
Lucy M. Palmer andGreg J. Stuart Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 0200, Australia
Correspondence should be addressed to Greg J. Stuart at the above address. Email: greg.stuart{at}anu.edu.au
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
Key words: cortex; axon; initial segment; myelin; oligodendrocyte; saltatory conduction
Received Nov. 9, 2005; revised Dec. 22, 2005; accepted Dec. 22, 2005.
Correspondence should be addressed to Greg J. Stuart at the above address. Email: greg.stuart{at}anu.edu.au
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