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:

Spike-timing-dependent synaptic plasticity depends on dendritic location

Abstract

In the neocortex, each neuron receives thousands of synaptic inputs distributed across an extensive dendritic tree. Although postsynaptic processing of each input is known to depend on its dendritic location1,2,3,4,5,6,7,8, it is unclear whether activity-dependent synaptic modification is also location-dependent. Here we report that both the magnitude and the temporal specificity of spike-timing-dependent synaptic modification9,10,11,12,13,14,15,16,17 vary along the apical dendrite of rat cortical layer 2/3 pyramidal neurons. At the distal dendrite, the magnitude of long-term potentiation is smaller, and the window of pre-/postsynaptic spike interval for long-term depression (LTD) is broader. The spike-timing window for LTD correlates with the window of action potential-induced suppression of NMDA (N-methyl-d-aspartate) receptors; this correlation applies to both their dendritic location-dependence and pharmacological properties. Presynaptic stimulation with partial blockade of NMDA receptors induced LTD and occluded further induction of spike-timing-dependent LTD, suggesting that NMDA receptor suppression underlies LTD induction. Computer simulation studies showed that the dendritic inhomogeneity of spike-timing-dependent synaptic modification leads to differential input selection at distal and proximal dendrites according to the temporal characteristics of presynaptic spike trains. Such location-dependent tuning of inputs, together with the dendritic heterogeneity of postsynaptic processing, could enhance the computational capacity of cortical pyramidal neurons.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Spike-timing-dependent synaptic modification at proximal and distal dendrites.
Figure 2: Suppression of EPSP by back-propagating action potential.
Figure 3: Pharmacological properties of NMDAR-EPSP suppression and LTD.
Figure 4: Synaptic modification induced by presynaptic stimulation under partial NMDAR blockade.
Figure 5: Simulation of location-dependent selection of synaptic inputs.

Similar content being viewed by others

References

  1. Stuart, G. & Spruston, N. Determinants of voltage attenuation in neocortical pyramidal neuron dendrites. J. Neurosci. 18, 3501–3510 (1998)

    Article  CAS  Google Scholar 

  2. Larkum, M. E., Zhu, J. J. & Sakmann, B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999)

    Article  ADS  CAS  Google Scholar 

  3. Cash, S. & Yuste, R. Linear summation of excitatory inputs by CA1 pyramidal neurons. Neuron 22, 383–394 (1999)

    Article  CAS  Google Scholar 

  4. Magee, J. C. Dendritic integration of excitatory synaptic input. Nature Rev. Neurosci. 1, 181–190 (2000)

    Article  CAS  Google Scholar 

  5. Segev, I. & London, M. Untangling dendrites with quantitative models. Science 290, 744–750 (2000)

    Article  ADS  CAS  Google Scholar 

  6. Hausser, M., Major, G. & Stuart, G. J. Differential shunting of EPSPs by action potentials. Science 291, 138–141 (2001)

    Article  ADS  CAS  Google Scholar 

  7. Tamas, G., Szabadics, J. & Somogyi, P. Cell type- and subcellular position-dependent summation of unitary postsynaptic potentials in neocortical neurons. J. Neurosci. 22, 740–747 (2002)

    Article  CAS  Google Scholar 

  8. Hausser, M. & Mel, B. Dendrites: bug or feature? Curr. Opin. Neurobiol. 13, 372–383 (2003)

    Article  CAS  Google Scholar 

  9. Magee, J. C. & Johnston, D. A. synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209–213 (1997)

    Article  CAS  Google Scholar 

  10. Markram, H., Lubke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997)

    Article  CAS  Google Scholar 

  11. Sourdet, V. & Debanne, D. The role of dendritic filtering in associative long-term synaptic plasticity. Learn. Mem. 6, 422–447 (1999)

    Article  CAS  Google Scholar 

  12. Feldman, D. E. Timing-based LTP and LTD at vertical inputs to layer II/III pyramidal cells in rat barrel cortex. Neuron 27, 45–56 (2000)

    Article  CAS  Google Scholar 

  13. Bi, G. & Poo, M. Synaptic modification by correlated activity: Hebb's postulate revisited. Annu. Rev. Neurosci. 24, 139–166 (2001)

    Article  CAS  Google Scholar 

  14. Froemke, R. C. & Dan, Y. Spike-timing-dependent synaptic modification induced by natural spike trains. Nature 416, 433–438 (2002)

    Article  ADS  CAS  Google Scholar 

  15. Watanabe, S., Hoffman, D. A., Migliore, M. & Johnston, D. Dendritic K + channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons. Proc. Natl Acad. Sci. USA 99, 8366–8371 (2002)

    Article  ADS  CAS  Google Scholar 

  16. Sjostrom, P. J., Turrigiano, G. G. & Nelson, S. B. Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors. Neuron 39, 641–654 (2003)

    Article  Google Scholar 

  17. Johnston, D. et al. Active dendrites, potassium channels and synaptic plasticity. Phil. Trans. R. Soc. Lond. B Biol. Sci. 358, 667–674 (2003)

    Article  CAS  Google Scholar 

  18. Stuart, G. J. & Hausser, M. Dendritic coincidence detection of EPSPs and action potentials. Nature Neurosci. 4, 63–71 (2001)

    Article  CAS  Google Scholar 

  19. Golding, N. L., Staff, N. P. & Spruston, N. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418, 326–331 (2002)

    Article  ADS  CAS  Google Scholar 

  20. Svoboda, K., Helmchen, F., Denk, W. & Tank, D. W. Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo . Nature Neurosci. 2, 65–73 (1999)

    Article  CAS  Google Scholar 

  21. Waters, J., Larkum, M., Sakmann, B. & Helmchen, F. Supralinear Ca2+ influx into dendritic tufts of layer 2/3 neocortical pyramidal neurons in vitro and in vivo . J. Neurosci. 22, 8558–8567 (2003)

    Article  Google Scholar 

  22. 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 

  23. Zilberter, Y., Kaiser, K. M. & Sakmann, B. Dendritic GABA release depresses excitatory transmission between layer 2/3 pyramidal and bitufted neurons in rat neocortex. Neuron 24, 979–988 (1999)

    Article  CAS  Google Scholar 

  24. Rosenmund, C., Feltz, A. & Westbrook, G. L. Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons. J. Neurophysiol. 73, 427–430 (1995)

    Article  CAS  Google Scholar 

  25. Tong, G., Shepherd, D. & Jahr, C. E. Synaptic desensitization of NMDA receptors by calcineurin. Science 267, 1510–1512 (1995)

    Article  ADS  CAS  Google Scholar 

  26. Umemiya, M., Chen, N., Raymond, L. A. & Murphy, T. H. A calcium-dependent feedback mechanism participates in shaping single NMDA miniature EPSCs. J. Neurosci. 21, 1–9 (2001)

    Article  CAS  Google Scholar 

  27. Zucker, R. S. Calcium- and activity-dependent synaptic plasticity. Curr. Opin. Neurobiol. 9, 305–313 (1999)

    Article  CAS  Google Scholar 

  28. Nevian, T. & Sakmann, B. Single spine Ca2+ signals evoked by coincident EPSPs and backpropagating action potentials in spiny stellate cells of layer 4 in the juvenile rat somatosensory barrel cortex. J. Neurosci. 24, 1689–1699 (2004)

    Article  CAS  Google Scholar 

  29. Song, S., Miller, K. D. & Abbott, L. F. Competitive Hebbian learning through spike-timing-dependent synaptic plasticity. Nature Neurosci. 3, 919–926 (2000)

    Article  CAS  Google Scholar 

  30. Archie, K. A. & Mel, B. W. A model for intradendritic computation of binocular disparity. Nature Neurosci. 3, 54–63 (2000)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank P. Ascher, G. Bi, L. Chen, M. Frerking, E. Isacoff, R. Kramer and R. Zucker for helpful discussions, and K. Arendt, K. Borges, N. Caporale and C. Nam for technical assistance. This work was supported by grants from the National Eye Institute and the Grass Foundation. R.C.F. is a recipient of the Howard Hughes Predoctoral Fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yang Dan.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1 to 6 and Legends. Supplementary Figure 1: This figure demonstrates that spike-timing-dependent LTD is independent of GABAA receptor-mediated inhibition both at proximal and distal dendritic locations. Supplementary Figure 2: This figure summarizes whole-cell recordings from apical dendrites of layer 2/3 pyramidal neurons. Spike amplitude and half-width are compared to the size and extent of the AP-EPSP suppression time window measured at different dendritic locations. Supplementary Figure 3: This figure shows the time windows for AP-induced suppression of AMPAR-EPSPs and NMDAR-EPSPs recorded at proximal and distal dendrites. The time course of suppression under both conditions is similar between dendritic and somatic recordings (see Figure 2). Supplementary Figure 4: This figure shows the effects on NMDAR-EPSP suppression and LTD of viral expression of a peptide corresponding to a region of the NR2A subunit critical for calcineurin-dependent NMDAR desensitization. Supplementary Figure 5: This figure shows Ca2+ imaging of apical dendrites from layer 2/3 pyramidal neurons. Distal regions of the dendrite exhibit higher amplitudes of AP-triggered Ca2+ increase than proximal regions. Enhancing the width of the back-propagating action potential with the transient K+ channel blocker 4-AP leads to larger Ca2+ influx at proximal dendrites. Supplementary Figure 6: This figure presents further analyses of the model shown in Figure 5. Example spike trains are shown, along with the cross-correlation of pre- and postsynaptic spike trains, and a four-compartment version of the model in Figure 5. (DOC 622 kb)

Supplementary Methods

This file describes the model of dendritic inhomogeneity of STDP used for the simulations in Figure 5 and Supplementary Figure 6. (DOC 64 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Froemke, R., Poo, Mm. & Dan, Y. Spike-timing-dependent synaptic plasticity depends on dendritic location. Nature 434, 221–225 (2005). https://doi.org/10.1038/nature03366

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature03366

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