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Slow integration leads to persistent action potential firing in distal axons of coupled interneurons

Nature Neuroscience volume 14, pages 200207 (2011) | Download Citation

Abstract

The conventional view of neurons is that synaptic inputs are integrated on a timescale of milliseconds to seconds in the dendrites, with action potential initiation occurring in the axon initial segment. We found a much slower form of integration that leads to action potential initiation in the distal axon, well beyond the initial segment. In a subset of rodent hippocampal and neocortical interneurons, hundreds of spikes, evoked over minutes, resulted in persistent firing that lasted for a similar duration. Although axonal action potential firing was required to trigger persistent firing, somatic depolarization was not. In paired recordings, persistent firing was not restricted to the stimulated neuron; it could also be produced in the unstimulated cell. Thus, these interneurons can slowly integrate spiking, share the output across a coupled network of axons and respond with persistent firing even in the absence of input to the soma or dendrites.

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Acknowledgements

We thank T. Klausberger, S. Layton and M. Wilson for providing in vivo spiking data, and M. Benton, M. Nusbaum and members of the Spruston laboratory for helpful discussion and comments on the manuscript. We also thank E. Grodinsky for interneuron reconstructions. Grant support was provided by the US National Institutes of Health (NS-046064 to N.S. and W.L.K.) and the National Alliance for Research on Schizophrenia and Depression (N.S.). M.E.J.S. was supported by a Presidential Fellowship from Northwestern University.

Author information

Affiliations

  1. Department of Neurobiology & Physiology, Northwestern University, Evanston, Illinois, USA.

    • Mark E J Sheffield
    • , Tyler K Best
    • , William L Kath
    •  & Nelson Spruston
  2. Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA.

    • Brett D Mensh
  3. Department of Engineering Sciences and Applied Math, Northwestern University, Evanston, Illinois, USA.

    • William L Kath

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Contributions

All authors participated in the design of the experiments and the analysis and interpretation of the data. M.E.J.S. and T.K.B. performed the experiments. W.L.K. performed the simulations. N.S. and B.D.M. wrote the manuscript with input from the other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Nelson Spruston.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7 and Supplementary Table 1

Videos

  1. 1.

    Supplementary Movie 1

    Simple model of axonal action potential propagation in a stylized axon.

  2. 2.

    Supplementary Movie 2

    Model of axonal action potential propagation in a full morphological model.

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DOI

https://doi.org/10.1038/nn.2728

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