Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study
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2022-10-03
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Journal Article
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Abstract
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.
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published
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Volume
16
Pages / Article No.
957255
Publisher
Frontiers Media
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Subject
homeostatic plasticity; AIS plasticity; HD-MEAs; biophysical modeling; random forest classifier; neighborhood components analysis (NCA); LTI systems; wide neural networks
Organisational unit
03684 - Hierlemann, Andreas / Hierlemann, Andreas
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Funding
694829 - Microtechnology and integrated microsystems to investigate neuronal networks across scales (EC)
188910 - Deciphering Neuronal Networks: Advancing Technology and Model Systems (SNF)
19-2 FEL-17 - Multi-modal intracellular and extracellular modeling and investigation of neuronal single-cell dynamics (ETHZ)
188910 - Deciphering Neuronal Networks: Advancing Technology and Model Systems (SNF)
19-2 FEL-17 - Multi-modal intracellular and extracellular modeling and investigation of neuronal single-cell dynamics (ETHZ)
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