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The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS
The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248374/ https://www.ncbi.nlm.nih.gov/pubmed/32508590 http://dx.doi.org/10.3389/fnmol.2020.00073 |
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author | Jara, Javier H. Sheets, Patrick L. Nigro, Maximiliano José Perić, Mina Brooks, Carolyn Heller, Daniel B. Martina, Marco Andjus, Pavle R. Ozdinler, P. Hande |
author_facet | Jara, Javier H. Sheets, Patrick L. Nigro, Maximiliano José Perić, Mina Brooks, Carolyn Heller, Daniel B. Martina, Marco Andjus, Pavle R. Ozdinler, P. Hande |
author_sort | Jara, Javier H. |
collection | PubMed |
description | The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1(G93A) mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1(G93A) and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies. |
format | Online Article Text |
id | pubmed-7248374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72483742020-06-05 The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS Jara, Javier H. Sheets, Patrick L. Nigro, Maximiliano José Perić, Mina Brooks, Carolyn Heller, Daniel B. Martina, Marco Andjus, Pavle R. Ozdinler, P. Hande Front Mol Neurosci Neuroscience The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1(G93A) mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1(G93A) and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies. Frontiers Media S.A. 2020-05-19 /pmc/articles/PMC7248374/ /pubmed/32508590 http://dx.doi.org/10.3389/fnmol.2020.00073 Text en Copyright © 2020 Jara, Sheets, Nigro, Perić, Brooks, Heller, Martina, Andjus and Ozdinler. http://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 Jara, Javier H. Sheets, Patrick L. Nigro, Maximiliano José Perić, Mina Brooks, Carolyn Heller, Daniel B. Martina, Marco Andjus, Pavle R. Ozdinler, P. Hande The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS |
title | The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS |
title_full | The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS |
title_fullStr | The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS |
title_full_unstemmed | The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS |
title_short | The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS |
title_sort | electrophysiological determinants of corticospinal motor neuron vulnerability in als |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248374/ https://www.ncbi.nlm.nih.gov/pubmed/32508590 http://dx.doi.org/10.3389/fnmol.2020.00073 |
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