Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Oct 15;93(21):11985–11990. doi: 10.1073/pnas.93.21.11985

Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells.

M Rapp 1, Y Yarom 1, I Segev 1
PMCID: PMC38170  PMID: 8876249

Abstract

Simultaneous recordings from the soma and apical dendrite of layer V neocortical pyramidal cells of young rats show that, for any location of current input, an evoked action potential (AP) always starts at the axon and then propagates actively, but decrementally, backward into the dendrites. This back-propagating AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly inactivating voltage-dependent Na+ channels in the soma and the apical dendrite. Investigation of detailed, biophysically constrained, models of reconstructed pyramidal cells shows the following. (i) The initiation of the AP first in the axon cannot be explained solely by morphological considerations; the axon must be more excitable than the soma and dendrites. (ii) The minimal Na+ channel density in the axon that fully accounts for the experimental results is about 20-times that of the soma. If -gNa in the axon hillock and initial segment is the same as in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. & Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2]], then -gNa in the more distal axonal regions is required to be about 40-times that of the soma. (iii) A backward propagating AP in weakly excitable dendrites can be modulated in a graded manner by background synaptic activity. The functional role of weakly excitable dendrites and a more excitable axon for forward synaptic integration and for backward, global, communication between the axon and the dendrites is discussed.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernander O., Douglas R. J., Martin K. A., Koch C. Synaptic background activity influences spatiotemporal integration in single pyramidal cells. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11569–11573. doi: 10.1073/pnas.88.24.11569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernander O., Koch C., Douglas R. J. Amplification and linearization of distal synaptic input to cortical pyramidal cells. J Neurophysiol. 1994 Dec;72(6):2743–2753. doi: 10.1152/jn.1994.72.6.2743. [DOI] [PubMed] [Google Scholar]
  3. Cummins T. R., Xia Y., Haddad G. G. Functional properties of rat and human neocortical voltage-sensitive sodium currents. J Neurophysiol. 1994 Mar;71(3):1052–1064. doi: 10.1152/jn.1994.71.3.1052. [DOI] [PubMed] [Google Scholar]
  4. Gutfreund Y., yarom Y., Segev I. Subthreshold oscillations and resonant frequency in guinea-pig cortical neurons: physiology and modelling. J Physiol. 1995 Mar 15;483(Pt 3):621–640. doi: 10.1113/jphysiol.1995.sp020611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamill O. P., Huguenard J. R., Prince D. A. Patch-clamp studies of voltage-gated currents in identified neurons of the rat cerebral cortex. Cereb Cortex. 1991 Jan-Feb;1(1):48–61. doi: 10.1093/cercor/1.1.48. [DOI] [PubMed] [Google Scholar]
  7. Hines M. A program for simulation of nerve equations with branching geometries. Int J Biomed Comput. 1989 Mar;24(1):55–68. doi: 10.1016/0020-7101(89)90007-x. [DOI] [PubMed] [Google Scholar]
  8. Häusser M., Stuart G., Racca C., Sakmann B. Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron. 1995 Sep;15(3):637–647. doi: 10.1016/0896-6273(95)90152-3. [DOI] [PubMed] [Google Scholar]
  9. Jaffe D. B., Johnston D., Lasser-Ross N., Lisman J. E., Miyakawa H., Ross W. N. The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurons. Nature. 1992 May 21;357(6375):244–246. doi: 10.1038/357244a0. [DOI] [PubMed] [Google Scholar]
  10. Jahr C. E., Stevens C. F. A quantitative description of NMDA receptor-channel kinetic behavior. J Neurosci. 1990 Jun;10(6):1830–1837. doi: 10.1523/JNEUROSCI.10-06-01830.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kim H. G., Beierlein M., Connors B. W. Inhibitory control of excitable dendrites in neocortex. J Neurophysiol. 1995 Oct;74(4):1810–1814. doi: 10.1152/jn.1995.74.4.1810. [DOI] [PubMed] [Google Scholar]
  12. Kim H. G., Connors B. W. Apical dendrites of the neocortex: correlation between sodium- and calcium-dependent spiking and pyramidal cell morphology. J Neurosci. 1993 Dec;13(12):5301–5311. doi: 10.1523/JNEUROSCI.13-12-05301.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Larkman A. U. Dendritic morphology of pyramidal neurones of the visual cortex of the rat: III. Spine distributions. J Comp Neurol. 1991 Apr 8;306(2):332–343. doi: 10.1002/cne.903060209. [DOI] [PubMed] [Google Scholar]
  14. Llinás R., Sugimori M. Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J Physiol. 1980 Aug;305:197–213. doi: 10.1113/jphysiol.1980.sp013358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Magee J. C., Johnston D. Characterization of single voltage-gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J Physiol. 1995 Aug 15;487(1):67–90. doi: 10.1113/jphysiol.1995.sp020862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Magee J. C., Johnston D. Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science. 1995 Apr 14;268(5208):301–304. doi: 10.1126/science.7716525. [DOI] [PubMed] [Google Scholar]
  17. Mainen Z. F., Joerges J., Huguenard J. R., Sejnowski T. J. A model of spike initiation in neocortical pyramidal neurons. Neuron. 1995 Dec;15(6):1427–1439. doi: 10.1016/0896-6273(95)90020-9. [DOI] [PubMed] [Google Scholar]
  18. Major G., Larkman A. U., Jonas P., Sakmann B., Jack J. J. Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices. J Neurosci. 1994 Aug;14(8):4613–4638. doi: 10.1523/JNEUROSCI.14-08-04613.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Markram H., Helm P. J., Sakmann B. Dendritic calcium transients evoked by single back-propagating action potentials in rat neocortical pyramidal neurons. J Physiol. 1995 May 15;485(Pt 1):1–20. doi: 10.1113/jphysiol.1995.sp020708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Markram H., Sakmann B. Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5207–5211. doi: 10.1073/pnas.91.11.5207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mel B. W. Synaptic integration in an excitable dendritic tree. J Neurophysiol. 1993 Sep;70(3):1086–1101. doi: 10.1152/jn.1993.70.3.1086. [DOI] [PubMed] [Google Scholar]
  22. Moore J. W., Stockbridge N., Westerfield M. On the site of impulse initiation in a neurone. J Physiol. 1983 Mar;336:301–311. doi: 10.1113/jphysiol.1983.sp014582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ross W. N., Werman R. Mapping calcium transients in the dendrites of Purkinje cells from the guinea-pig cerebellum in vitro. J Physiol. 1987 Aug;389:319–336. doi: 10.1113/jphysiol.1987.sp016659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schiller J., Helmchen F., Sakmann B. Spatial profile of dendritic calcium transients evoked by action potentials in rat neocortical pyramidal neurones. J Physiol. 1995 Sep 15;487(Pt 3):583–600. doi: 10.1113/jphysiol.1995.sp020902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Softky W. Sub-millisecond coincidence detection in active dendritic trees. Neuroscience. 1994 Jan;58(1):13–41. doi: 10.1016/0306-4522(94)90154-6. [DOI] [PubMed] [Google Scholar]
  26. Spruston N., Schiller Y., Stuart G., Sakmann B. Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science. 1995 Apr 14;268(5208):297–300. doi: 10.1126/science.7716524. [DOI] [PubMed] [Google Scholar]
  27. Stern P., Edwards F. A., Sakmann B. Fast and slow components of unitary EPSCs on stellate cells elicited by focal stimulation in slices of rat visual cortex. J Physiol. 1992 Apr;449:247–278. doi: 10.1113/jphysiol.1992.sp019085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stuart G. J., Dodt H. U., Sakmann B. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch. 1993 Jun;423(5-6):511–518. doi: 10.1007/BF00374949. [DOI] [PubMed] [Google Scholar]
  29. Stuart G. J., Sakmann B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature. 1994 Jan 6;367(6458):69–72. doi: 10.1038/367069a0. [DOI] [PubMed] [Google Scholar]
  30. Stuart G., Sakmann B. Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons. Neuron. 1995 Nov;15(5):1065–1076. doi: 10.1016/0896-6273(95)90095-0. [DOI] [PubMed] [Google Scholar]
  31. Stuart G., Spruston N. Probing dendritic function with patch pipettes. Curr Opin Neurobiol. 1995 Jun;5(3):389–394. doi: 10.1016/0959-4388(95)80053-0. [DOI] [PubMed] [Google Scholar]
  32. Traub R. D., Miles R. Pyramidal cell-to-inhibitory cell spike transduction explicable by active dendritic conductances in inhibitory cell. J Comput Neurosci. 1995 Dec;2(4):291–298. doi: 10.1007/BF00961441. [DOI] [PubMed] [Google Scholar]
  33. Turner R. W., Maler L., Deerinck T., Levinson S. R., Ellisman M. H. TTX-sensitive dendritic sodium channels underlie oscillatory discharge in a vertebrate sensory neuron. J Neurosci. 1994 Nov;14(11 Pt 1):6453–6471. doi: 10.1523/JNEUROSCI.14-11-06453.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Westenbroek R. E., Merrick D. K., Catterall W. A. Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons. Neuron. 1989 Dec;3(6):695–704. doi: 10.1016/0896-6273(89)90238-9. [DOI] [PubMed] [Google Scholar]
  35. Wollner D. A., Catterall W. A. Localization of sodium channels in axon hillocks and initial segments of retinal ganglion cells. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8424–8428. doi: 10.1073/pnas.83.21.8424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yuste R., Denk W. Dendritic spines as basic functional units of neuronal integration. Nature. 1995 Jun 22;375(6533):682–684. doi: 10.1038/375682a0. [DOI] [PubMed] [Google Scholar]
  37. Yuste R., Gutnick M. J., Saar D., Delaney K. R., Tank D. W. Ca2+ accumulations in dendrites of neocortical pyramidal neurons: an apical band and evidence for two functional compartments. Neuron. 1994 Jul;13(1):23–43. doi: 10.1016/0896-6273(94)90457-x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES