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Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings

Human induced pluripotent stem cells (hiPSCs) are a promising approach to study neurological and neuropsychiatric diseases. Most methods to record the activity of these cells have major drawbacks as they are invasive or they do not allow single cell resolution. Genetically encoded voltage indicators...

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Autores principales: Alich, Therese C., Röderer, Pascal, Szalontai, Balint, Golcuk, Kurt, Tariq, Shahan, Peitz, Michael, Brüstle, Oliver, Mody, Istvan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887032/
https://www.ncbi.nlm.nih.gov/pubmed/36733665
http://dx.doi.org/10.3389/fncel.2022.1039957
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author Alich, Therese C.
Röderer, Pascal
Szalontai, Balint
Golcuk, Kurt
Tariq, Shahan
Peitz, Michael
Brüstle, Oliver
Mody, Istvan
author_facet Alich, Therese C.
Röderer, Pascal
Szalontai, Balint
Golcuk, Kurt
Tariq, Shahan
Peitz, Michael
Brüstle, Oliver
Mody, Istvan
author_sort Alich, Therese C.
collection PubMed
description Human induced pluripotent stem cells (hiPSCs) are a promising approach to study neurological and neuropsychiatric diseases. Most methods to record the activity of these cells have major drawbacks as they are invasive or they do not allow single cell resolution. Genetically encoded voltage indicators (GEVIs) open the path to high throughput visualization of undisturbed neuronal activity. However, conventional GEVIs perturb membrane integrity through inserting multiple copies of transmembrane domains into the plasma membrane. To circumvent large add-ons to the plasma membrane, we used a minimally invasive novel hybrid dark quencher GEVI to record the physiological and pathological firing patterns of hiPSCs-derived sensory neurons from patients with inherited erythromelalgia, a chronic pain condition associated with recurrent attacks of redness and swelling in the distal extremities. We observed considerable differences in action potential firing patterns between patient and control neurons that were previously overlooked with other recording methods. Our system also performed well in hiPSC-derived forebrain neurons where it detected spontaneous synchronous bursting behavior, thus opening the path to future applications in other cell types and disease models including Parkinson’s disease, Alzheimer’s disease, epilepsy, and schizophrenia, conditions associated with disturbances of neuronal activity and synchrony.
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spelling pubmed-98870322023-02-01 Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings Alich, Therese C. Röderer, Pascal Szalontai, Balint Golcuk, Kurt Tariq, Shahan Peitz, Michael Brüstle, Oliver Mody, Istvan Front Cell Neurosci Neuroscience Human induced pluripotent stem cells (hiPSCs) are a promising approach to study neurological and neuropsychiatric diseases. Most methods to record the activity of these cells have major drawbacks as they are invasive or they do not allow single cell resolution. Genetically encoded voltage indicators (GEVIs) open the path to high throughput visualization of undisturbed neuronal activity. However, conventional GEVIs perturb membrane integrity through inserting multiple copies of transmembrane domains into the plasma membrane. To circumvent large add-ons to the plasma membrane, we used a minimally invasive novel hybrid dark quencher GEVI to record the physiological and pathological firing patterns of hiPSCs-derived sensory neurons from patients with inherited erythromelalgia, a chronic pain condition associated with recurrent attacks of redness and swelling in the distal extremities. We observed considerable differences in action potential firing patterns between patient and control neurons that were previously overlooked with other recording methods. Our system also performed well in hiPSC-derived forebrain neurons where it detected spontaneous synchronous bursting behavior, thus opening the path to future applications in other cell types and disease models including Parkinson’s disease, Alzheimer’s disease, epilepsy, and schizophrenia, conditions associated with disturbances of neuronal activity and synchrony. Frontiers Media S.A. 2023-01-17 /pmc/articles/PMC9887032/ /pubmed/36733665 http://dx.doi.org/10.3389/fncel.2022.1039957 Text en Copyright © 2023 Alich, Röderer, Szalontai, Golcuk, Tariq, Peitz, Brüstle and Mody. 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
Alich, Therese C.
Röderer, Pascal
Szalontai, Balint
Golcuk, Kurt
Tariq, Shahan
Peitz, Michael
Brüstle, Oliver
Mody, Istvan
Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
title Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
title_full Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
title_fullStr Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
title_full_unstemmed Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
title_short Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
title_sort bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887032/
https://www.ncbi.nlm.nih.gov/pubmed/36733665
http://dx.doi.org/10.3389/fncel.2022.1039957
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