Article | Published:

NMDA spikes enhance action potential generation during sensory input

Nature Neuroscience volume 17, pages 383390 (2014) | Download Citation

Abstract

Recent evidence in vitro suggests that the tuft dendrites of pyramidal neurons are capable of evoking local NMDA receptor–dependent electrogenesis, so-called NMDA spikes. However, it has so far proved difficult to demonstrate their existence in vivo. Moreover, it is not clear whether NMDA spikes are relevant to the output of pyramidal neurons. We found that local NMDA spikes occurred in tuft dendrites of layer 2/3 pyramidal neurons both spontaneously and following sensory input, and had a large influence on the number of output action potentials. Using two-photon activation of an intracellular caged NMDA receptor antagonist (tc-MK801), we found that isolated NMDA spikes typically occurred in multiple branches simultaneously and that sensory stimulation substantially increased their probability. Our results demonstrate that NMDA receptors have a vital role in coupling the tuft region of the layer 2/3 pyramidal neuron to the cell body, enhancing the effectiveness of layer 1 input.

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Acknowledgements

We thank F. Haiss and B. Weber for designing the custom-made two-photon microscope, and D. Langer and F. Helmchen for the imaging software Helioscan. We also thank S. Murphy and R. Min for their comments on the manuscript. We further acknowledge the GENIE Program and the Janelia Farm Research Campus for the use of GCaMP6. This work was supported by SystemsX.ch (NeuroChoice), Swiss National Science Foundation (31003A_130694), the Whitaker International Program and the DFG (EXC 257 NeuroCure).

Author information

Affiliations

  1. Florey Institute, University of Melbourne, Melbourne, Victoria, Australia.

    • Lucy M Palmer
  2. Physiologisches Institut, Universität Bern, Bern, Switzerland.

    • Lucy M Palmer
    •  & Matthew E Larkum
  3. NeuroCure Cluster of Excellence, Humboldt University, Berlin, Germany.

    • Lucy M Palmer
    •  & Matthew E Larkum
  4. Bioengineering Department, California Institute of Technology, Pasadena, California, USA.

    • Adam S Shai
  5. Department of Chemistry, University of Oxford, Oxford, UK.

    • James E Reeve
    •  & Harry L Anderson
  6. Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, UK.

    • Ole Paulsen

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Contributions

L.M.P. and M.E.L. designed, performed and analyzed the experiments. A.S.S. performed the computer simulations. J.E.R., H.L.A. and O.P. synthesized and provided the caged-MK801. L.M.P. and M.E.L. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Lucy M Palmer.

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DOI

https://doi.org/10.1038/nn.3646

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