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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Neuroinformatics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fninf.2022.957255/full |
| _version_ | 1811242912051101696 |
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| author | Sreedhar S. Kumar Tobias Gänswein Alessio P. Buccino Xiaohan Xue Julian Bartram Vishalini Emmenegger Andreas Hierlemann |
| author_facet | Sreedhar S. Kumar Tobias Gänswein Alessio P. Buccino Xiaohan Xue Julian Bartram Vishalini Emmenegger Andreas Hierlemann |
| author_sort | Sreedhar S. Kumar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T13:58:06Z |
| format | Article |
| id | doaj.art-ab0c30c4a45545f0b7ba19997868debb |
| institution | Directory Open Access Journal |
| issn | 1662-5196 |
| language | English |
| last_indexed | 2024-04-12T13:58:06Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroinformatics |
| spelling | doaj.art-ab0c30c4a45545f0b7ba19997868debb2022-12-22T03:30:18ZengFrontiers Media S.A.Frontiers in Neuroinformatics1662-51962022-10-011610.3389/fninf.2022.957255957255Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational studySreedhar S. KumarTobias GänsweinAlessio P. BuccinoXiaohan XueJulian BartramVishalini EmmeneggerAndreas HierlemannDespite 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.https://www.frontiersin.org/articles/10.3389/fninf.2022.957255/fullhomeostatic plasticityAIS plasticityHD-MEAsbiophysical modelingrandom forest classifierneighborhood components analysis (NCA) |
| spellingShingle | Sreedhar S. Kumar Tobias Gänswein Alessio P. Buccino Xiaohan Xue Julian Bartram Vishalini Emmenegger Andreas Hierlemann Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study Frontiers in Neuroinformatics homeostatic plasticity AIS plasticity HD-MEAs biophysical modeling random forest classifier neighborhood components analysis (NCA) |
| 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 | homeostatic plasticity AIS plasticity HD-MEAs biophysical modeling random forest classifier neighborhood components analysis (NCA) |
| url | https://www.frontiersin.org/articles/10.3389/fninf.2022.957255/full |
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