Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

NMDA spikes in basal dendrites of cortical pyramidal neurons

Abstract

Basal dendrites are a major target for synaptic inputs innervating cortical pyramidal neurons1. At present little is known about signal processing in these fine dendrites. Here we show that co-activation of clustered neighbouring basal inputs initiated local dendritic spikes, which resulted in a 5.9 ± 1.5 mV (peak) and 64.4 ± 19.8 ms (half-width) cable-filtered voltage change at the soma that amplified the somatic voltage response by 226 ± 46%. These spikes were accompanied by large calcium transients restricted to the activated dendritic segment. In contrast to conventional sodium or calcium spikes, these spikes were mediated mostly by NMDA (N -methyl-D-aspartate) receptor channels, which contributed at least 80% of the total charge. The ionic mechanism of these NMDA spikes may allow ‘dynamic spike-initiation zones’, set by the spatial distribution of glutamate pre-bound to NMDA receptors, which in turn would depend on recent and ongoing activity in the cortical network. In addition, NMDA spikes may serve as a powerful mechanism for modification of the cortical network by inducing long-term strengthening of co-activated neighbouring inputs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Local spikes in basal dendrites evoked by focal glutamate uncaging.
Figure 2: Voltage-gated sodium and calcium channels participate in initiation of basal dendritic spikes.
Figure 3: NMDA receptor channels are the main charge carriers mediating basal dendritic spikes.
Figure 4: Basal dendritic NMDA spikes evoked by focal synaptic stimulation.
Figure 5: Synaptically evoked basal dendritic spikes are accompanied by large local calcium influx.

Similar content being viewed by others

References

  1. Larkman, A. U. Dendritic morphology of pyramidal neurons of the rat: Spine distribution. J. Comp. Neurol. 306, 332– 343 (1991).

    Article  CAS  Google Scholar 

  2. Cash, S. & Yuste, R. Input summation by cultured pyramidal neurons is linear and position independent. J. Neurosci. 18, 10–15 (1998).

    Article  CAS  Google Scholar 

  3. Cash, S. & Yuste, R. Linear summation of excitatory inputs by CA1 pyramidal neurons. Neuron 22, 383 –94 (1999).

    Article  CAS  Google Scholar 

  4. Schiller, J., Schiller, Y., Stuart, G. & Sakmann, B. Calcium action potentials in apical dendrites of neocortical pyramidal neurons in rat brain slices. J. Physiol. 505, 605– 616 (1997).

    Article  CAS  Google Scholar 

  5. Bliss, T. V. P. & Collingridge, G. L. A synaptic model of memory: Long term potentiation in the hippocampus. Nature 361, 31–39 ( 1993).

    Article  ADS  CAS  Google Scholar 

  6. Schiller, J., Schiller, Y. & Clapham, D. E. NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation. Nature Neurosci. 1, 114–118 ( 1998).

    Article  CAS  Google Scholar 

  7. 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. Pflug. Arch. Eur. J. Physiol. 423, 511–518 (1993).

    Article  CAS  Google Scholar 

  8. Koester, H. J. & Sakmann, B. Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials. Proc. Natl Acad. Sci. USA 95, 9596–9601 (1998).

    Article  ADS  CAS  Google Scholar 

  9. Hines, M. L. & Carnevale, N. T. The NEURON simulation environment. Neural Comput. 9, 1179– 1209 (1997).

    Article  CAS  Google Scholar 

  10. Major, G., Larkman, A. U., Jonas, P., Sakmann, B. & Jack, J. J. B. Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices. J. Neurosci. 14, 4613–4638 (1994).

    Article  CAS  Google Scholar 

  11. Ascher, P. & Nowak, L. The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurons in culture. J. Physiol. 399, 247–266 (1988).

    Article  CAS  Google Scholar 

  12. Hestrin, S., Nicoll, R. A., Perkel, D. J. & Sah, P. Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J. Physiol. 422, 203–225 (1990).

    Article  CAS  Google Scholar 

  13. Brodin, L., Traven, H. G. C., Lansner, A., Wallen, P. & Ekeberg, O. Computer simulations of N-methyl-D-aspartate receptor-induced membrane properties in a neuron model. J. Neurophysiol . 66, 473–484 ( 1991).

    Article  CAS  Google Scholar 

  14. Brown, A. M., Schwindt, P. C. & Crill, W. E. Voltage dependence and activation kinetics of pharmacologically defined components of the high-threshold calcium current in rat neocortical neurons. J. Neurophysiol. 70, 1530– 1543 (1993).

    Article  CAS  Google Scholar 

  15. Jonas, P., Major, G. & Sakmann, B. Quantal components of unitary EPSCs at the mossy fiber synapse on CA3 pyramidal cells of rat hippocampus. J. Physiol. 472, 615–663 (1993).

    Article  CAS  Google Scholar 

  16. Martina, M. & Jonas, P. Functional differences in Na+ channel gating between fast-spiking interneurons and principal neurons of rat hippocampus. J. Physiol. 505, 593 –603 (1997).

    Article  CAS  Google Scholar 

  17. Destexhe, A., Neubig, M., Ulrich, D. & Huguenard, J. Dendritic low-threshold calcium currents in thalamic relay cells. J. Neurosci. 18, 3574–3588 (1998).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank. D. E. Clapham, F. Prendergast, B. Sakmann, W. Denk and D. Tank for assistance and support, A. Larkman for reconstructing the cell used in the simulations, and M. Hausser and G. Stuart for reading early versions of the manuscript. In addition we thank the Mayo Foundation, Leo & Frances Kogan endowment fund (J.S.), Wellcome Trust, Lucent Technologies and Marine Biological Laboratory (G.M.) for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jackie Schiller.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schiller, J., Major, G., Koester, H. et al. NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature 404, 285–289 (2000). https://doi.org/10.1038/35005094

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35005094

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing