Theoretical relation between axon initial segment geometry and excitability

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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

1. Hu W
2. Bean B
(2019) Responses to axonal current injection in cortical layer 5 pyramidal neurons
Zenodo DOI: 10.5281/zenodo.3539296.

https://zenodo.org/record/3539297#.Xc0yxjJKhBx

Article and author information

Author details

Sarah Goethals

Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France

Competing interests
The authors declare that no competing interests exist.
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.

"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.

Copyright

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.