Letter | Published:

Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo

Nature volume 503, pages 115120 (07 November 2013) | Download Citation

Subjects

This article has been updated

Abstract

Neuronal dendrites are electrically excitable: they can generate regenerative events such as dendritic spikes in response to sufficiently strong synaptic input1,2,3. Although such events have been observed in many neuronal types4,5,6,7,8,9, it is not well understood how active dendrites contribute to the tuning of neuronal output in vivo. Here we show that dendritic spikes increase the selectivity of neuronal responses to the orientation of a visual stimulus (orientation tuning). We performed direct patch-clamp recordings from the dendrites of pyramidal neurons in the primary visual cortex of lightly anaesthetized and awake mice, during sensory processing. Visual stimulation triggered regenerative local dendritic spikes that were distinct from back-propagating action potentials. These events were orientation tuned and were suppressed by either hyperpolarization of membrane potential or intracellular blockade of NMDA (N-methyl-d-aspartate) receptors. Both of these manipulations also decreased the selectivity of subthreshold orientation tuning measured at the soma, thus linking dendritic regenerative events to somatic orientation tuning. Together, our results suggest that dendritic spikes that are triggered by visual input contribute to a fundamental cortical computation: enhancing orientation selectivity in the visual cortex. Thus, dendritic excitability is an essential component of behaviourally relevant computations in neurons.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Change history

  • 06 November 2012

    Reference 13 has been replaced.

References

  1. 1.

    & Active dendrites: colorful wings of the mysterious butterflies. Trends Neurosci. 31, 309–316 (2008)

  2. 2.

    & Dendritic computation. Annu. Rev. Neurosci. 28, 503–532 (2005)

  3. 3.

    Pyramidal neurons: dendritic structure and synaptic integration. Nature Rev. Neurosci. 9, 206–221 (2008)

  4. 4.

    , & A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999)

  5. 5.

    , , & NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature 404, 285–289 (2000)

  6. 6.

    , , & In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nature Neurosci. 2, 989–996 (1999)

  7. 7.

    , , & Dendritic spikes and their inhibition in alligator Purkinje cells. Science 160, 1132–1135 (1968)

  8. 8.

    , & Dendritic spikes are enhanced by cooperative network activity in the intact hippocampus. J. Neurosci. 18, 3919–3928 (1998)

  9. 9.

    , , , & Ca2+ accumulations in dendrites of neocortical pyramidal neurons: an apical band and evidence for two functional compartments. Neuron 13, 23–43 (1994)

  10. 10.

    , & Dendritic discrimination of temporal input sequences in cortical neurons. Science 329, 1671–1675 (2010)

  11. 11.

    & EPSP-IPSP interactions in cat visual cortex studied with in vivo whole-cell patch recording. J. Neurosci. 12, 1262–1274 (1992)

  12. 12.

    , , & Postsynaptic potentials in cat visual cortex: dependence on polarization. Neuroreport 3, 679–682 (1992)

  13. 13.

    , & Visually evoked calcium action potentials in cat striate cortex. Nature 378, 612–616 (1995)

  14. 14.

    & Receptive fields of single neurones in the cat’s striate cortex. J. Physiol. (Lond.) 148, 574–591 (1959)

  15. 15.

    , , & Dendritic spikes in apical dendrites of neocortical layer 2/3 pyramidal neurons. J. Neurosci. 27, 8999–9008 (2007)

  16. 16.

    & Background synaptic activity is sparse in neocortex. J. Neurosci. 26, 8267–8277 (2006)

  17. 17.

    & Highly selective receptive fields in mouse visual cortex. J. Neurosci. 28, 7520–7536 (2008)

  18. 18.

    , & Cortical action potential backpropagation explains spike threshold variability and rapid-onset kinetics. J. Neurosci. 28, 7260–7272 (2008)

  19. 19.

    , , & Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo. Nature Neurosci. 2, 65–73 (1999)

  20. 20.

    , , , & Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex. J. Neurosci. 31, 12339–12350 (2011)

  21. 21.

    , , & Dendritic organization of sensory input to cortical neurons in vivo. Nature 464, 1307–1312 (2010)

  22. 22.

    , & Computational subunits in thin dendrites of pyramidal cells. Nature Neurosci. 7, 621–627 (2004)

  23. 23.

    , , , & Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo. Nature 490, 397–401 (2012)

  24. 24.

    Synaptic integration in an excitable dendritic tree. J. Neurophysiol. 70, 1086–1101 (1993)

  25. 25.

    & Parallel processing of visual space by neighboring neurons in mouse visual cortex. Nature Neurosci. 13, 1144–1149 (2010)

  26. 26.

    et al. Sparse coding and high-order correlations in fine-scale cortical networks. Nature 466, 617–621 (2010)

  27. 27.

    , , , & Sensitivity to perturbations in vivo implies high noise and suggests rate coding in cortex. Nature 466, 123–127 (2010)

  28. 28.

    et al. Nonlinear dendritic integration of sensory and motor input during an active sensing task. Nature 492, 247–251 (2012)

  29. 29.

    et al. Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex. Nature Neurosci. 15, 607–612 (2012)

  30. 30.

    , , , & The organization of two new cortical interneuronal circuits. Nature Neurosci. 16, 210–218 (2013)

  31. 31.

    The psychophysics toolbox. Spat. Vis. 10, 433–436 (1997)

  32. 32.

    The VideoToolbox software for visual psychophysics: transforming numbers into movies. Spat. Vis. 10, 437–442 (1997)

  33. 33.

    , , , & Targeted patch-clamp recordings and single-cell electroporation of unlabeled neurons in vivo. Nature Methods 5, 61–67 (2008)

  34. 34.

    & Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. J. Neurosci. 10, 3178–3182 (1990)

  35. 35.

    , , & Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study. Nature Neurosci. 10, 206–214 (2007)

  36. 36.

    , & Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. J. Physiol. (Lond.) 482, 325–352 (1995)

  37. 37.

    , & ScanImage: flexible software for operating laser scanning microscopes. Biomed. Eng. Online 2, 13 (2003)

  38. 38.

    & A multidimensional version of the Kolomogorov–Smirnov test. Mon. Not. R. Astron. Soc. 225, 155–170 (1987)

Download references

Acknowledgements

We are grateful to B. Clark, P. Latham, M. London, D. Ringach, A. Roth, C. Schmidt-Hieber and C. Wilms for discussions and comments on the manuscript. This work was supported by the following: a Long-Term Fellowship and a Career Development Award from the Human Frontier Science Program and a Klingenstein Fellowship (S.L.S.); a Helen Lyng White Fellowship (I.T.S.); a Wellcome Trust and Royal Society Fellowship and MRC Programme Leader Track (T.B.); and by grants from the Wellcome Trust, ERC and Gatsby Charitable Foundation (M.H.).

Author information

Affiliations

  1. Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK

    • Spencer L. Smith
    • , Ikuko T. Smith
    • , Tiago Branco
    •  & Michael Häusser
  2. Department of Cell Biology and Physiology and Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA

    • Spencer L. Smith
    •  & Ikuko T. Smith
  3. Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 0QH, UK

    • Tiago Branco

Authors

  1. Search for Spencer L. Smith in:

  2. Search for Ikuko T. Smith in:

  3. Search for Tiago Branco in:

  4. Search for Michael Häusser in:

Contributions

S.L.S. and M.H. conceived and designed the experiments. S.L.S. and I.T.S. performed the experiments. S.L.S. analysed the data. T.B. designed and carried out the compartmental modelling. S.L.S., I.T.S., T.B. and M.H. interpreted the data and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Spencer L. Smith or Michael Häusser.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains a Supplementary Note and additional references. This file was replaced on 6 November 2013.

Videos

  1. 1.

    The propagation of voltage in the compartmental model during synaptic activation

    Background input was continuously active, and signal synapses were activated at 8 Hz for 200 ms (100 ms after the start of the trace). The traces show the local voltage at the indicated dendrites, together with the somatic voltage. During the period of high synaptic input local dendritic spikes are elicited in multiple regions of the dendritic tree, and eventually lead to a somatic action potential the backpropagates globally. Note how all of the global spikes are preceded by at least one dendritic spike in a region of the dendritic tree.

  2. 2.

    Slow motion video of the same trial shown in Video 1, highlighting the activity in dendrite 3

    Note that the first two global spikes are immediately preceded by local spikes in this dendrite, and that while the last dendritic spike does not directly trigger a somatic action potential it leads to a significant charge build up in the soma that facilitates the subsequent somatic firing.

  3. 3.

    Slow motion video of the same trial shown in Video 1, highlighting the activity in dendrite 1

    Note that dendrite 1 fires bursts of spikes at frequencies >50 Hz.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature12600

Further reading

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.