KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation

Autores
Stupniki, Sofia; Bayasgalan, Tsogbadrakh; Kovács, Adrienn; Csemer, Andrea; Szentesi, Peter; Pocsai, Krisztina; Dionisio, Leonardo Raul; Spitzmaul, Guillermo Federico; Pal, Bálazs
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The M-current is a voltage-gated potassium current generated by channels composed by KCNQ2-5 subunits. The pedunculopontine nucleus (PPN) is part of the Reticular Activating System (RAS), associated with sleep regulation. As little is known about the composition, subcellular location and physiological implication of the M-current in PPN, our aim was to demonstrate the presence of KCNQ4 in the PPN, and its contribution to the neuronal function of this nucleus. We used a transgenic mouse lacking KCNQ4 expression (KO) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). Using qPCR, immunofluorescence and electrophysiology on brain slices, we demonstrated that only a subpopulation of cholinergic neurons (around 27%), located on the external limits of the PPN has KCNQ4-mediated M-current. We also found that KCNQ4 regulates the expression of other KCNQ subunits. In KO mice, the expression profile changed drastically respect with the WT: Kcnq2 expression decreased, Kcnq3 increase and Kcnq5 disappeared. To study the influence of KCNQ4 on circadian rhythm we used behavioral testing. KO mice exhibited alterations in the activity cycles showing a higher sensitivity to changes in the light-darkness cycles. In summary, we found that some PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm. Since the PPN is affected in certain neurological diseases, KCNQ4 might be a potential pharmacological target.
Fil: Stupniki, Sofia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bayasgalan, Tsogbadrakh. University of Debrecen; Hungría
Fil: Kovács, Adrienn. University of Debrecen; Hungría
Fil: Csemer, Andrea. University of Debrecen; Hungría
Fil: Szentesi, Peter. University of Debrecen; Hungría
Fil: Pocsai, Krisztina. University of Debrecen; Hungría
Fil: Dionisio, Leonardo Raul. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. University of Debrecen; Hungría
Fil: Pal, Bálazs. University of Debrecen; Hungría
XXXV Reunión Anual Sociedad Argentina de Investigación en Neurociencia 2020
Argentina
Sociedad Argentina de Investigación en Neurociencia
Materia
KNCQ4
PPN
circadian rhythm
RAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/155895

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulationStupniki, SofiaBayasgalan, TsogbadrakhKovács, AdriennCsemer, AndreaSzentesi, PeterPocsai, KrisztinaDionisio, Leonardo RaulSpitzmaul, Guillermo FedericoPal, BálazsKNCQ4PPNcircadian rhythmRAShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The M-current is a voltage-gated potassium current generated by channels composed by KCNQ2-5 subunits. The pedunculopontine nucleus (PPN) is part of the Reticular Activating System (RAS), associated with sleep regulation. As little is known about the composition, subcellular location and physiological implication of the M-current in PPN, our aim was to demonstrate the presence of KCNQ4 in the PPN, and its contribution to the neuronal function of this nucleus. We used a transgenic mouse lacking KCNQ4 expression (KO) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). Using qPCR, immunofluorescence and electrophysiology on brain slices, we demonstrated that only a subpopulation of cholinergic neurons (around 27%), located on the external limits of the PPN has KCNQ4-mediated M-current. We also found that KCNQ4 regulates the expression of other KCNQ subunits. In KO mice, the expression profile changed drastically respect with the WT: Kcnq2 expression decreased, Kcnq3 increase and Kcnq5 disappeared. To study the influence of KCNQ4 on circadian rhythm we used behavioral testing. KO mice exhibited alterations in the activity cycles showing a higher sensitivity to changes in the light-darkness cycles. In summary, we found that some PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm. Since the PPN is affected in certain neurological diseases, KCNQ4 might be a potential pharmacological target.Fil: Stupniki, Sofia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bayasgalan, Tsogbadrakh. University of Debrecen; HungríaFil: Kovács, Adrienn. University of Debrecen; HungríaFil: Csemer, Andrea. University of Debrecen; HungríaFil: Szentesi, Peter. University of Debrecen; HungríaFil: Pocsai, Krisztina. University of Debrecen; HungríaFil: Dionisio, Leonardo Raul. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. University of Debrecen; HungríaFil: Pal, Bálazs. University of Debrecen; HungríaXXXV Reunión Anual Sociedad Argentina de Investigación en Neurociencia 2020ArgentinaSociedad Argentina de Investigación en NeurocienciaSociedad Argentina de Investigación en NeurocienciaBramajo, PabloCabllero, PaulCeriani, Silvina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/155895KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation; XXXV Reunión Anual Sociedad Argentina de Investigación en Neurociencia 2020; Argentina; 2020; 282-282CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.saneurociencias.org.ar/congresos-san/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:57:55Zoai:ri.conicet.gov.ar:11336/155895instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:57:55.671CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
title KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
spellingShingle KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
Stupniki, Sofia
KNCQ4
PPN
circadian rhythm
RAS
title_short KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
title_full KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
title_fullStr KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
title_full_unstemmed KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
title_sort KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation
dc.creator.none.fl_str_mv Stupniki, Sofia
Bayasgalan, Tsogbadrakh
Kovács, Adrienn
Csemer, Andrea
Szentesi, Peter
Pocsai, Krisztina
Dionisio, Leonardo Raul
Spitzmaul, Guillermo Federico
Pal, Bálazs
author Stupniki, Sofia
author_facet Stupniki, Sofia
Bayasgalan, Tsogbadrakh
Kovács, Adrienn
Csemer, Andrea
Szentesi, Peter
Pocsai, Krisztina
Dionisio, Leonardo Raul
Spitzmaul, Guillermo Federico
Pal, Bálazs
author_role author
author2 Bayasgalan, Tsogbadrakh
Kovács, Adrienn
Csemer, Andrea
Szentesi, Peter
Pocsai, Krisztina
Dionisio, Leonardo Raul
Spitzmaul, Guillermo Federico
Pal, Bálazs
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bramajo, Pablo
Cabllero, Paul
Ceriani, Silvina
dc.subject.none.fl_str_mv KNCQ4
PPN
circadian rhythm
RAS
topic KNCQ4
PPN
circadian rhythm
RAS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The M-current is a voltage-gated potassium current generated by channels composed by KCNQ2-5 subunits. The pedunculopontine nucleus (PPN) is part of the Reticular Activating System (RAS), associated with sleep regulation. As little is known about the composition, subcellular location and physiological implication of the M-current in PPN, our aim was to demonstrate the presence of KCNQ4 in the PPN, and its contribution to the neuronal function of this nucleus. We used a transgenic mouse lacking KCNQ4 expression (KO) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). Using qPCR, immunofluorescence and electrophysiology on brain slices, we demonstrated that only a subpopulation of cholinergic neurons (around 27%), located on the external limits of the PPN has KCNQ4-mediated M-current. We also found that KCNQ4 regulates the expression of other KCNQ subunits. In KO mice, the expression profile changed drastically respect with the WT: Kcnq2 expression decreased, Kcnq3 increase and Kcnq5 disappeared. To study the influence of KCNQ4 on circadian rhythm we used behavioral testing. KO mice exhibited alterations in the activity cycles showing a higher sensitivity to changes in the light-darkness cycles. In summary, we found that some PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm. Since the PPN is affected in certain neurological diseases, KCNQ4 might be a potential pharmacological target.
Fil: Stupniki, Sofia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bayasgalan, Tsogbadrakh. University of Debrecen; Hungría
Fil: Kovács, Adrienn. University of Debrecen; Hungría
Fil: Csemer, Andrea. University of Debrecen; Hungría
Fil: Szentesi, Peter. University of Debrecen; Hungría
Fil: Pocsai, Krisztina. University of Debrecen; Hungría
Fil: Dionisio, Leonardo Raul. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. University of Debrecen; Hungría
Fil: Pal, Bálazs. University of Debrecen; Hungría
XXXV Reunión Anual Sociedad Argentina de Investigación en Neurociencia 2020
Argentina
Sociedad Argentina de Investigación en Neurociencia
description The M-current is a voltage-gated potassium current generated by channels composed by KCNQ2-5 subunits. The pedunculopontine nucleus (PPN) is part of the Reticular Activating System (RAS), associated with sleep regulation. As little is known about the composition, subcellular location and physiological implication of the M-current in PPN, our aim was to demonstrate the presence of KCNQ4 in the PPN, and its contribution to the neuronal function of this nucleus. We used a transgenic mouse lacking KCNQ4 expression (KO) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). Using qPCR, immunofluorescence and electrophysiology on brain slices, we demonstrated that only a subpopulation of cholinergic neurons (around 27%), located on the external limits of the PPN has KCNQ4-mediated M-current. We also found that KCNQ4 regulates the expression of other KCNQ subunits. In KO mice, the expression profile changed drastically respect with the WT: Kcnq2 expression decreased, Kcnq3 increase and Kcnq5 disappeared. To study the influence of KCNQ4 on circadian rhythm we used behavioral testing. KO mice exhibited alterations in the activity cycles showing a higher sensitivity to changes in the light-darkness cycles. In summary, we found that some PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm. Since the PPN is affected in certain neurological diseases, KCNQ4 might be a potential pharmacological target.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/155895
KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation; XXXV Reunión Anual Sociedad Argentina de Investigación en Neurociencia 2020; Argentina; 2020; 282-282
CONICET Digital
CONICET
url http://hdl.handle.net/11336/155895
identifier_str_mv KCNQ4 in the reticular activating system (RAS): contribution to the circadian rhythm modulation; XXXV Reunión Anual Sociedad Argentina de Investigación en Neurociencia 2020; Argentina; 2020; 282-282
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.saneurociencias.org.ar/congresos-san/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencia
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencia
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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