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Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study
Despite being composed of highly plastic neurons with extensive positive feedback, the nervous system maintains stable overall function. To keep activity within bounds, it relies on a set of negative feedback mechanisms that can induce stabilizing adjustments and that are collectively termed “homeos...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613690/ https://www.ncbi.nlm.nih.gov/pubmed/36221258 http://dx.doi.org/10.3389/fninf.2022.957255 |
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author | Kumar, Sreedhar S. Gänswein, Tobias Buccino, Alessio P. Xue, Xiaohan Bartram, Julian Emmenegger, Vishalini Hierlemann, Andreas |
author_facet | Kumar, Sreedhar S. Gänswein, Tobias Buccino, Alessio P. Xue, Xiaohan Bartram, Julian Emmenegger, Vishalini Hierlemann, Andreas |
author_sort | Kumar, Sreedhar S. |
collection | PubMed |
description | Despite being composed of highly plastic neurons with extensive positive feedback, the nervous system maintains stable overall function. To keep activity within bounds, it relies on a set of negative feedback mechanisms that can induce stabilizing adjustments and that are collectively termed “homeostatic plasticity.” Recently, a highly excitable microdomain, located at the proximal end of the axon—the axon initial segment (AIS)—was found to exhibit structural modifications in response to activity perturbations. Though AIS plasticity appears to serve a homeostatic purpose, many aspects governing its expression and its functional role in regulating neuronal excitability remain elusive. A central challenge in studying the phenomenon is the rich heterogeneity of its expression (distal/proximal relocation, shortening, lengthening) and the variability of its functional role. A potential solution is to track AISs of a large number of neurons over time and attempt to induce structural plasticity in them. To this end, a promising approach is to use extracellular electrophysiological readouts to track a large number of neurons at high spatiotemporal resolution by means of high-density microelectrode arrays (HD-MEAs). However, an analysis framework that reliably identifies specific activity signatures that uniquely map on to underlying microstructural changes is missing. In this study, we assessed the feasibility of such a task and used the distal relocation of the AIS as an exemplary problem. We used sophisticated computational models to systematically explore the relationship between incremental changes in AIS positions and the specific consequences observed in simulated extracellular field potentials. An ensemble of feature changes in the extracellular fields that reliably characterize AIS plasticity was identified. We trained models that could detect these signatures with remarkable accuracy. Based on these findings, we propose a hybrid analysis framework that could potentially enable high-throughput experimental studies of activity-dependent AIS plasticity using HD-MEAs. |
format | Online Article Text |
id | pubmed-7613690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76136902022-10-10 Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study Kumar, Sreedhar S. Gänswein, Tobias Buccino, Alessio P. Xue, Xiaohan Bartram, Julian Emmenegger, Vishalini Hierlemann, Andreas Front Neuroinform Neuroscience Despite being composed of highly plastic neurons with extensive positive feedback, the nervous system maintains stable overall function. To keep activity within bounds, it relies on a set of negative feedback mechanisms that can induce stabilizing adjustments and that are collectively termed “homeostatic plasticity.” Recently, a highly excitable microdomain, located at the proximal end of the axon—the axon initial segment (AIS)—was found to exhibit structural modifications in response to activity perturbations. Though AIS plasticity appears to serve a homeostatic purpose, many aspects governing its expression and its functional role in regulating neuronal excitability remain elusive. A central challenge in studying the phenomenon is the rich heterogeneity of its expression (distal/proximal relocation, shortening, lengthening) and the variability of its functional role. A potential solution is to track AISs of a large number of neurons over time and attempt to induce structural plasticity in them. To this end, a promising approach is to use extracellular electrophysiological readouts to track a large number of neurons at high spatiotemporal resolution by means of high-density microelectrode arrays (HD-MEAs). However, an analysis framework that reliably identifies specific activity signatures that uniquely map on to underlying microstructural changes is missing. In this study, we assessed the feasibility of such a task and used the distal relocation of the AIS as an exemplary problem. We used sophisticated computational models to systematically explore the relationship between incremental changes in AIS positions and the specific consequences observed in simulated extracellular field potentials. An ensemble of feature changes in the extracellular fields that reliably characterize AIS plasticity was identified. We trained models that could detect these signatures with remarkable accuracy. Based on these findings, we propose a hybrid analysis framework that could potentially enable high-throughput experimental studies of activity-dependent AIS plasticity using HD-MEAs. Frontiers Media S.A. 2022-10-03 /pmc/articles/PMC7613690/ /pubmed/36221258 http://dx.doi.org/10.3389/fninf.2022.957255 Text en Copyright © 2022 Kumar, Gänswein, Buccino, Xue, Bartram, Emmenegger and Hierlemann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Kumar, Sreedhar S. Gänswein, Tobias Buccino, Alessio P. Xue, Xiaohan Bartram, Julian Emmenegger, Vishalini Hierlemann, Andreas Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study |
title | Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study |
title_full | Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study |
title_fullStr | Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study |
title_full_unstemmed | Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study |
title_short | Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study |
title_sort | tracking axon initial segment plasticity using high-density microelectrode arrays: a computational study |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613690/ https://www.ncbi.nlm.nih.gov/pubmed/36221258 http://dx.doi.org/10.3389/fninf.2022.957255 |
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