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Ion channel properties underlying axonal action potential initiation in pyramidal neurons

Nature Neuroscience volume 5, pages 533–538 (2002)Cite this article

An Erratum to this article was published on 01 October 2002

Abstract

A high density of Na+ channels in the axon hillock, or initial segment, is believed to determine the threshold for action potential initiation in neurons. Here we report evidence for an alternative mechanism that lowers the threshold in the axon. We investigated properties and distributions of ion channels in outside-out patches from axons and somata of layer 5 pyramidal neurons in rat neocortical slices. Na+ channels in axonal patches (〈30 μm from the soma) were activated by 7 mV less depolarization than were somatic Na+ channels. A-type K+ channels, which were prominent in somatic and dendritic patches, were rarely seen in axonal patches. We incorporated these findings into numerical simulations which indicate that biophysical properties of axonal channels, rather than a high density of channels in the initial segment, are most likely to determine the lowest threshold for action potential initiation.

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Figure 1: Total ensemble currents in outside-out patches from visually identified somata and axons of neocortical layer 5 pyramidal neurons.
Figure 2: Na+ channel properties differ between the soma and axon.
Figure 3: Effect of Na+ channel properties on action potential threshold: computer simulations.
Figure 4: Spatial patterns of action potential initiation: computer simulations.
Figure 5: Threshold increases when a pyramidal neuron is cut at the end of the initial segment.

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References

  1. Mel, B.W. Information processing in dendritic trees. Neural Comput. 6, 1031–1085 (1994).

    Article  Google Scholar 

  2. Koch, C. Biophysics of Computation: Information Processing in Single Neurons (Oxford Univ. Press, New York, 1999).

    Google Scholar 

  3. Shadlen, M.N. & Newsome, W.T. The variable discharge of cortical neurons: implications for connectivity, computation, and information coding. J. Neurosci. 18, 3870–3896 (1998).

    Article  CAS  Google Scholar 

  4. Regehr, W.G. & Armstrong, C.M. Where does it all begin? Curr. Biol. 4, 436–439 (1994).

    Article  CAS  Google Scholar 

  5. Adams, P.R. The platonic neuron gets the hots. Curr. Biol. 2, 625–627 (1992).

    Article  CAS  Google Scholar 

  6. Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D.W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161–165 (1997).

    Article  CAS  Google Scholar 

  7. Turner, R.W., Meyers, D.E.R., Richardson, T.L. & Barker, J.L. The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons. J. Neurosci. 11, 2270–2280 (1991).

    Article  CAS  Google Scholar 

  8. Andreasen, M. & Lambert, J.D.C. Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus. J. Physiol. (Lond.) 483, 421–441 (1995).

    Article  CAS  Google Scholar 

  9. Hoffman, D.A., Magee, J.C., Colbert, C.M. & Johnston, D. K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387, 869–875 (1997).

    Article  CAS  Google Scholar 

  10. Stuart, G., Schiller, J. & Sakmann, B. Action potential initiation and propagation in rat neocortical pyramidal neurons. J. Physiol. (Lond.) 505, 617–632 (1997).

    Article  CAS  Google Scholar 

  11. Spruston, N., Schiller, Y., Stuart, G. & Sakmann, B. Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268, 297–300 (1995).

    Article  CAS  Google Scholar 

  12. Moore, J.W. & Westerfield, M. Action potential propagation and threshold parameters in inhomogeneous regions of squid axon. J. Physiol. (Lond.) 336, 285–300 (1983).

    Article  CAS  Google Scholar 

  13. Moore, J.W., Stockbridge, N. & Westerfield, M. On the site of impulse initiation in a neurone. J. Physiol. (Lond.) 336, 301–311 (1983).

    Article  CAS  Google Scholar 

  14. Luscher, H.R. & Larkum, M.E. Modeling action potential initiation and back-propagation in dendrites of cultured rat motoneurons. J. Neurophysiol. 80, 715–729 (1998).

    Article  CAS  Google Scholar 

  15. Farinas, I. & DeFelipe, J. Patterns of synaptic input on corticocortical and corticothalamic cells in the cat visual cortex II. The axon initial segment. J. Comp. Neurol. 304, 70–77 (1991).

    Article  CAS  Google Scholar 

  16. Palay, S.L., Sotelo, C., Peters, A. & Orkland, P.M. The axon hillock and the initial segment. J. Cell Biol. 37, 193–201 (1968).

    Article  Google Scholar 

  17. Dodge, F.A. & Cooley, J.W. Action potential of the motoneuron. IBM J. Res. Dev. 17, 219–229 (1973).

    Article  Google Scholar 

  18. Mainen, Z.F., Joerges, J., Huguenard, J.R. & Sejnowski, T.J. A model of spike initiation in neocortical pyramidal neurons. Neuron 15, 1427–1439 (1995).

    Article  CAS  Google Scholar 

  19. Rapp, M., Yarom, Y. & Segev, I. Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells. Proc. Natl. Acad. Sci. USA 93, 11985–11990 (1996).

    Article  CAS  Google Scholar 

  20. Catterall, W.A. Localization of sodium channels in cultured neural cells. J. Neurosci. 1, 777–783 (1981).

    Article  CAS  Google Scholar 

  21. Angelides, K.J., Elmer, L.W., Loftus, D. & Elson, E. Distribution and lateral mobility of voltage-dependent sodium channels in neurons. J. Cell Biol. 106, 1911–1924 (1988).

    Article  CAS  Google Scholar 

  22. Alessandri-Haber, N. et al. Specific distribution of sodium channels in axons of rat embryo spinal motoneurones. J. Physiol. (Lond.) 518, 203–214 (1999).

    Article  CAS  Google Scholar 

  23. Colbert, C.M. & Johnston, D. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons. J. Neurosci. 16, 6676–6686 (1996).

    Article  CAS  Google Scholar 

  24. Stuart, G.J. & Sakmann, B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367, 69–72 (1994).

    Article  CAS  Google Scholar 

  25. Rasband, M.N., Trimmer, J.S., Peles, E., Levinson, S.R. & Shrager, P. K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve. J. Neurocytol. 28, 319–331 (1999).

    Article  CAS  Google Scholar 

  26. Golding, N.L. & Spruston, N. Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons. Neuron 21, 1189–1200 (1998).

    Article  CAS  Google Scholar 

  27. Kloosterman, F., Peloquin, P. & Leung, L.S. Apical and basal orthodromic population spikes in hippocampal CA1 in vivo show different origins and patterns of propagation. J. Neurophysiol. 86, 2435–2444 (2001).

    Article  CAS  Google Scholar 

  28. Carras, P.L., Coleman, P.A. & Miller, R.F. Site of action potential initiation in amphibian retinal ganglion cells. J. Neurophysiol. 67, 292–304 (1992).

    Article  CAS  Google Scholar 

  29. Zecevic, D. Multiple spike-initiation zones in single neurons revealed by voltage-sensitive dyes. Nature 381, 322–325 (1996).

    Article  CAS  Google Scholar 

  30. Edwards, E. & Ottoson, D. The site of impulse initiation in a nerve cell of a crustacean stretch receptor. J. Physiol. (Lond.) 143, 138–148 (1958).

    Article  CAS  Google Scholar 

  31. Gogan, P., Gueritaud, J.P. & Tyc-Dumont, S. Comparison of antidromic and orthodromic action potentials of identified motor axons in the cat's brain stem. J. Physiol. (Lond.) 335, 205–220 (1983).

    Article  CAS  Google Scholar 

  32. Chavez-Noriega, L.E., Halliwell, J.V. & Bliss, T.V.P. A decrease in firing threshold observed after induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices. Exp. Brain Res. 79, 633–641 (1990).

    Article  CAS  Google Scholar 

  33. Astman, N., Gutnick, M.J. & Fleidervish, I.A. Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices. J. Neurophysiol. 80, 1547–1551 (1998).

    Article  CAS  Google Scholar 

  34. Matsumoto, E. & Rosenbluth, J. Plasma membrane structure at the axon hillock, initial segment and cell body of frog dorsal root ganglion cells. J. Neurocytol. 14, 731–747 (1985).

    Article  CAS  Google Scholar 

  35. Stuart, G., Spruston, N., Sakmann, B. & Hausser, M. Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci. 20, 125–131 (1997).

    Article  CAS  Google Scholar 

  36. Magee, J.C. Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons. J. Neurosci. 18, 7613–7624 (1998).

    Article  CAS  Google Scholar 

  37. Johnston, D., Magee, J.C., Colbert, C.M. & Christie, B.R. Active properties of neuronal dendrites. Annu. Rev. Neurosci. 19, 165–186 (1996).

    Article  CAS  Google Scholar 

  38. Buhl, E.H. et al. Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus. J. Neurophysiol. 71, 1289–1307 (1994).

    Article  CAS  Google Scholar 

  39. Cobb, S.R., Buhl, E.H., Halasy, K., Paulsen, O. & Somogyi, P. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 75–78 (1995).

    Article  CAS  Google Scholar 

  40. Hines, M. NEURON—a program for simulation of nerve equations. in Neural Systems: Analysis and Modeling (ed. Eeckman, F.) 127–136 (Kluwer, Norwell, Massachusetts, 1993).

    Chapter  Google Scholar 

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Acknowledgements

This work was supported by a National Institute of Neurological Disorders and Stroke (NINDS) grant (NS36982) to C.M.C. We thank J. Stringer, D. Johnston, M. Rea, A. Eskin, G. Cahill and S. Dryer for reading earlier versions of the manuscript, and L. Cleary for the use of the Neurolucida system.

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  1. Department of Biology and Biochemistry, University of Houston, 4800 Calhoun Road, Houston, 77204-5513, Texas, USA

    Costa M. Colbert & Enhui Pan

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Correspondence to Costa M. Colbert.

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Colbert, C., Pan, E. Ion channel properties underlying axonal action potential initiation in pyramidal neurons. Nat Neurosci 5, 533–538 (2002). https://doi.org/10.1038/nn0602-857

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