High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons

Abstract Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such...

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Main Authors: Christopher A. Quintanilla, Zachary Fitzgerald, Omar Kashow, Mihailo S. Radojicic, Emel Ulupinar, Dila Bitlis, Baris Genc, Pavle Andjus, Wim van Drongelen, P. Hande Ozdinler
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-83883-6
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author Christopher A. Quintanilla
Zachary Fitzgerald
Omar Kashow
Mihailo S. Radojicic
Emel Ulupinar
Dila Bitlis
Baris Genc
Pavle Andjus
Wim van Drongelen
P. Hande Ozdinler
author_facet Christopher A. Quintanilla
Zachary Fitzgerald
Omar Kashow
Mihailo S. Radojicic
Emel Ulupinar
Dila Bitlis
Baris Genc
Pavle Andjus
Wim van Drongelen
P. Hande Ozdinler
author_sort Christopher A. Quintanilla
collection DOAJ
description Abstract Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology. However, a high-spatiotemporal resolution on our understanding of their functional health and connectivity is lacking. Here, we combine optical imaging with high-density microelectrode array (HD-MEA) system enabling single cell resolution and utilize UCHL1-eGFP mice to bring cell-type specificity to our understanding of the electrophysiological features of healthy CSMN, as they mature and form network connections with other cortical neurons, in vitro. This novel approach lays the foundation for future cell-type specific analyses of CSMN that are diseased due to different underlying causes with cellular precision, and it will allow the assessment of their functional response to compound treatment, especially for drug discovery efforts in upper motor neuron diseases.
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spelling doaj-art-bf54698dc7a642639d7900019679a9802025-01-05T12:22:58ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-024-83883-6High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neuronsChristopher A. Quintanilla0Zachary Fitzgerald1Omar Kashow2Mihailo S. Radojicic3Emel Ulupinar4Dila Bitlis5Baris Genc6Pavle Andjus7Wim van Drongelen8P. Hande Ozdinler9Department of Neurology, Feinberg School of Medicine, Northwestern UniversityDepartment of Neurology, Feinberg School of Medicine, Northwestern UniversityDepartment of Neurology, Feinberg School of Medicine, Northwestern UniversityInstitute for Physiology and Biochemistry “Jean Giaja”, Faculty of Biology, University of BelgradeDepartment of Neurology, Feinberg School of Medicine, Northwestern UniversityDepartment of Neurology, Feinberg School of Medicine, Northwestern UniversityDepartment of Neurology, Feinberg School of Medicine, Northwestern UniversityInstitute for Physiology and Biochemistry “Jean Giaja”, Faculty of Biology, University of BelgradePediatric Neurology, The University of ChicagoDepartment of Neurology, Feinberg School of Medicine, Northwestern UniversityAbstract Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology. However, a high-spatiotemporal resolution on our understanding of their functional health and connectivity is lacking. Here, we combine optical imaging with high-density microelectrode array (HD-MEA) system enabling single cell resolution and utilize UCHL1-eGFP mice to bring cell-type specificity to our understanding of the electrophysiological features of healthy CSMN, as they mature and form network connections with other cortical neurons, in vitro. This novel approach lays the foundation for future cell-type specific analyses of CSMN that are diseased due to different underlying causes with cellular precision, and it will allow the assessment of their functional response to compound treatment, especially for drug discovery efforts in upper motor neuron diseases.https://doi.org/10.1038/s41598-024-83883-6
spellingShingle Christopher A. Quintanilla
Zachary Fitzgerald
Omar Kashow
Mihailo S. Radojicic
Emel Ulupinar
Dila Bitlis
Baris Genc
Pavle Andjus
Wim van Drongelen
P. Hande Ozdinler
High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
Scientific Reports
title High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
title_full High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
title_fullStr High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
title_full_unstemmed High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
title_short High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
title_sort high density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons
url https://doi.org/10.1038/s41598-024-83883-6
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