Cargando…
Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit
The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep–wakefulness cycle. The M-current is a voltage-gated potassium current modulated m...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352570/ https://www.ncbi.nlm.nih.gov/pubmed/34381336 http://dx.doi.org/10.3389/fncel.2021.707789 |
_version_ | 1783736209597530112 |
---|---|
author | Bayasgalan, T. Stupniki, S. Kovács, A. Csemer, A. Szentesi, P. Pocsai, K. Dionisio, L. Spitzmaul, G. Pál, B. |
author_facet | Bayasgalan, T. Stupniki, S. Kovács, A. Csemer, A. Szentesi, P. Pocsai, K. Dionisio, L. Spitzmaul, G. Pál, B. |
author_sort | Bayasgalan, T. |
collection | PubMed |
description | The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep–wakefulness cycle. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current. In the central nervous system, KCNQ4 expression is restricted to certain brainstem structures such as the RAS nuclei. Here, we investigated the presence and functional significance of KCNQ4 in the PPN by behavioral studies and the gene and protein expressions and slice electrophysiology using a mouse model lacking KCNQ4 expression. We found that this mouse has alterations in the adaptation to changes in light–darkness cycles, representing the potential role of KCNQ4 in the regulation of the sleep–wakefulness cycle. As cholinergic neurons from the PPN participate in the regulation of this cycle, we investigated whether the cholinergic PPN might also possess functional KCNQ4 subunits. Although the M-current is an electrophysiological hallmark of cholinergic neurons, only a subpopulation of them had KCNQ4-dependent M-current. Interestingly, the absence of the KCNQ4 subunit altered the expression patterns of the other KCNQ subunits in the PPN. We also determined that, in wild-type animals, the cholinergic inputs of the PPN modulated the M-current, and these in turn can modulate the level of synchronization between neighboring PPN neurons. Taken together, the KCNQ4 subunit is present in a subpopulation of PPN cholinergic neurons, and it may contribute to the regulation of the sleep–wakefulness cycle. |
format | Online Article Text |
id | pubmed-8352570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83525702021-08-10 Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit Bayasgalan, T. Stupniki, S. Kovács, A. Csemer, A. Szentesi, P. Pocsai, K. Dionisio, L. Spitzmaul, G. Pál, B. Front Cell Neurosci Neuroscience The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep–wakefulness cycle. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current. In the central nervous system, KCNQ4 expression is restricted to certain brainstem structures such as the RAS nuclei. Here, we investigated the presence and functional significance of KCNQ4 in the PPN by behavioral studies and the gene and protein expressions and slice electrophysiology using a mouse model lacking KCNQ4 expression. We found that this mouse has alterations in the adaptation to changes in light–darkness cycles, representing the potential role of KCNQ4 in the regulation of the sleep–wakefulness cycle. As cholinergic neurons from the PPN participate in the regulation of this cycle, we investigated whether the cholinergic PPN might also possess functional KCNQ4 subunits. Although the M-current is an electrophysiological hallmark of cholinergic neurons, only a subpopulation of them had KCNQ4-dependent M-current. Interestingly, the absence of the KCNQ4 subunit altered the expression patterns of the other KCNQ subunits in the PPN. We also determined that, in wild-type animals, the cholinergic inputs of the PPN modulated the M-current, and these in turn can modulate the level of synchronization between neighboring PPN neurons. Taken together, the KCNQ4 subunit is present in a subpopulation of PPN cholinergic neurons, and it may contribute to the regulation of the sleep–wakefulness cycle. Frontiers Media S.A. 2021-07-26 /pmc/articles/PMC8352570/ /pubmed/34381336 http://dx.doi.org/10.3389/fncel.2021.707789 Text en Copyright © 2021 Bayasgalan, Stupniki, Kovács, Csemer, Szentesi, Pocsai, Dionisio, Spitzmaul and Pál. 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 Bayasgalan, T. Stupniki, S. Kovács, A. Csemer, A. Szentesi, P. Pocsai, K. Dionisio, L. Spitzmaul, G. Pál, B. Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit |
title | Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit |
title_full | Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit |
title_fullStr | Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit |
title_full_unstemmed | Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit |
title_short | Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit |
title_sort | alteration of mesopontine cholinergic function by the lack of kcnq4 subunit |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352570/ https://www.ncbi.nlm.nih.gov/pubmed/34381336 http://dx.doi.org/10.3389/fncel.2021.707789 |
work_keys_str_mv | AT bayasgalant alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT stupnikis alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT kovacsa alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT csemera alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT szentesip alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT pocsaik alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT dionisiol alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT spitzmaulg alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit AT palb alterationofmesopontinecholinergicfunctionbythelackofkcnq4subunit |