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Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach
To establish and exploit novel biomarkers of demyelinating diseases requires a mechanistic understanding of axonal propagation. Here, we present a novel computational framework called the stochastic spike-diffuse-spike (SSDS) model for assessing the effects of demyelination on axonal transmission. I...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542900/ https://www.ncbi.nlm.nih.gov/pubmed/31147800 http://dx.doi.org/10.1186/s13408-019-0071-6 |
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author | Naud, Richard Longtin, André |
author_facet | Naud, Richard Longtin, André |
author_sort | Naud, Richard |
collection | PubMed |
description | To establish and exploit novel biomarkers of demyelinating diseases requires a mechanistic understanding of axonal propagation. Here, we present a novel computational framework called the stochastic spike-diffuse-spike (SSDS) model for assessing the effects of demyelination on axonal transmission. It models transmission through nodal and internodal compartments with two types of operations: a stochastic integrate-and-fire operation captures nodal excitability and a linear filtering operation describes internodal propagation. The effects of demyelinated segments on the probability of transmission, transmission delay and spike time jitter are explored. We argue that demyelination-induced impedance mismatch prevents propagation mostly when the action potential leaves a demyelinated region, not when it enters a demyelinated region. In addition, we model sodium channel remodeling as a homeostatic control of nodal excitability. We find that the effects of mild demyelination on transmission probability and delay can be largely counterbalanced by an increase in excitability at the nodes surrounding the demyelination. The spike timing jitter, however, reflects the level of demyelination whether excitability is fixed or is allowed to change in compensation. This jitter can accumulate over long axons and leads to a broadening of the compound action potential, linking microscopic defects to a mesoscopic observable. Our findings articulate why action potential jitter and compound action potential dispersion can serve as potential markers of weak and sporadic demyelination. |
format | Online Article Text |
id | pubmed-6542900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-65429002019-06-19 Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach Naud, Richard Longtin, André J Math Neurosci Research To establish and exploit novel biomarkers of demyelinating diseases requires a mechanistic understanding of axonal propagation. Here, we present a novel computational framework called the stochastic spike-diffuse-spike (SSDS) model for assessing the effects of demyelination on axonal transmission. It models transmission through nodal and internodal compartments with two types of operations: a stochastic integrate-and-fire operation captures nodal excitability and a linear filtering operation describes internodal propagation. The effects of demyelinated segments on the probability of transmission, transmission delay and spike time jitter are explored. We argue that demyelination-induced impedance mismatch prevents propagation mostly when the action potential leaves a demyelinated region, not when it enters a demyelinated region. In addition, we model sodium channel remodeling as a homeostatic control of nodal excitability. We find that the effects of mild demyelination on transmission probability and delay can be largely counterbalanced by an increase in excitability at the nodes surrounding the demyelination. The spike timing jitter, however, reflects the level of demyelination whether excitability is fixed or is allowed to change in compensation. This jitter can accumulate over long axons and leads to a broadening of the compound action potential, linking microscopic defects to a mesoscopic observable. Our findings articulate why action potential jitter and compound action potential dispersion can serve as potential markers of weak and sporadic demyelination. Springer Berlin Heidelberg 2019-05-30 /pmc/articles/PMC6542900/ /pubmed/31147800 http://dx.doi.org/10.1186/s13408-019-0071-6 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Naud, Richard Longtin, André Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
title | Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
title_full | Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
title_fullStr | Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
title_full_unstemmed | Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
title_short | Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
title_sort | linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542900/ https://www.ncbi.nlm.nih.gov/pubmed/31147800 http://dx.doi.org/10.1186/s13408-019-0071-6 |
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