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.
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).
Responses to axonal current injection in cortical layer 5 pyramidal neuronsZenodo DOI: 10.5281/zenodo.3539296.
- Sarah Goethals
- Romain Brette
- 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.
- Frances K Skinner, Krembil Research Institute, University Health Network, Canada
© 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.
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