Theoretical relation between axon initial segment geometry and excitability

  1. Sarah Goethals
  2. Romain Brette  Is a corresponding author
  1. Sorbonne Université, INSERM, CNRS, France

Abstract

In most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment (AIS). Both position and length of the AIS vary across and within neuron types, with activity, development and pathology. What is the impact of AIS geometry on excitability? Direct empirical assessment has proven difficult because of the many potential confounding factors. Here we carried a principled theoretical analysis to answer this question. We provide a simple formula relating AIS geometry and sodium conductance density to the somatic voltage threshold. A distal shift of the AIS normally produces a (modest) increase in excitability, but we explain how this pattern can reverse if a hyperpolarizing current is present at the AIS, due to resistive coupling with the soma. This work provides a theoretical tool to assess the significance of structural AIS plasticity for electrical function.

Data availability

Code to generate all figures is available on GitHub: https://github.com/romainbrette/AIS-geometry-and-excitability-2019Electrophysiological data analyzed in Fig. 2 has been uploaded on Zenodo: https://zenodo.org/record/3539297#.Xc0WbjJKhBw (DOI: 10.5281/zenodo.3539296), on behalf of Prof. Bean (Data from Hu & Bean, 2018).Digitized data used in Fig. 3 have been uploaded on GitHub (link above).

The following previously published data sets were used

Article and author information

Author details

  1. Sarah Goethals

    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Romain Brette

    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
    For correspondence
    romain.brette@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0110-1623

Funding

Agence Nationale de la Recherche (ANR-14-CE13-0003)

  • Sarah Goethals
  • Romain Brette

Ecole des Neurosciences de Paris (N/A)

  • Sarah Goethals
  • Romain Brette

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Frances K Skinner, Krembil Research Institute, University Health Network, Canada

Publication history

  1. Received: November 7, 2019
  2. Accepted: March 30, 2020
  3. Accepted Manuscript published: March 30, 2020 (version 1)
  4. Version of Record published: April 20, 2020 (version 2)

Copyright

© 2020, Goethals & Brette

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,275
    Page views
  • 390
    Downloads
  • 14
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sarah Goethals
  2. Romain Brette
(2020)
Theoretical relation between axon initial segment geometry and excitability
eLife 9:e53432.
https://doi.org/10.7554/eLife.53432
  1. Further reading

Further reading

    1. Computational and Systems Biology
    2. Evolutionary Biology
    Grzegorz Kudla, Marcin Plech
    Insight

    Using a neural network to predict how green fluorescent proteins respond to genetic mutations illuminates properties that could help design new proteins.

    1. Computational and Systems Biology
    2. Genetics and Genomics
    Noushin Hadadi et al.
    Tools and Resources

    Thermal adaptation is an extensively used intervention for enhancing or suppressing thermogenic and mitochondrial activity in adipose tissues. As such, it has been suggested as a potential lifestyle intervention for body weight maintenance. While the metabolic consequences of thermal acclimation are not limited to the adipose tissues, the impact on the rest of the tissues in context of their gene expression profile remains unclear. Here, we provide a systematic characterization of the effects in a comparative multi-tissue RNA sequencing approach following exposure of mice to 10 °C, 22 °C, or 34 °C in a panel of organs consisting of spleen, bone marrow, spinal cord, brain, hypothalamus, ileum, liver, quadriceps, subcutaneous-, visceral- and brown adipose tissues. We highlight that transcriptional responses to temperature alterations exhibit a high degree of tissue-specificity both at the gene level and at GO enrichment gene sets, and show that the tissue-specificity is not directed by the distinct basic gene expression pattern exhibited by the various organs. Our study places the adaptation of individual tissues to different temperatures in a whole-organism framework and provides integrative transcriptional analysis necessary for understanding the temperature-mediated biological programming.