Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system

Autores
Stupniki, Sofia; Dionisio, Leonardo Raul; Perotti, Gabriel Tomás; Barila, Esteban Pablo; Dye, Leandro; Kovacs, Adrienn; Bayasgalan, Tsogbadrakh; Pal, Balazs; Spitzmaul, Guillermo Federico
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The pedunculopontine nucleus (PPN) is part of the reticular activating system (RAS) which is associated with sleep regulation. The PPN has cholinergic and non-cholinergic neurons. A hallmark of the PPN-cholinergic neurons is the M-current, a slowly activating, non-inactivating voltage-gated potassium current. KCNQ2 to 5 subunit alone or in combination are responsible for the M-current. Our aim was to investigate the contribution of the KCNQ4 subunit to PPN neuronal function. We used a transgenic mouse model for KCNQ4 (knock-out (KO)) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). We analyzed KCNQ4 expression by real-time PCR and its localization using immunofluorescence. We also studied the M-current by electrophysiology on brain slices, the contribution of KCNQ4 to neuronal activity and its influence on circadian rhythm. We found a weak mRNA expression of KCNQ4 in PPN and the protein was located only on cholinergic neurons of the external limits of the nucleus. M-current was present in most of cholinergic neurons in WT animals, but absent in 40% of them in the KO ones. These last also exhibited behavioral alterations in the activity cycles showing a 5-hour increase and a higher sensitivity to changes in the light/darkness cycles. In summary, we found that only a subpopulation of PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm through the activity of the RAS system.
Fil: Stupniki, Sofia. 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: Dionisio, Leonardo Raul. 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
Fil: Perotti, Gabriel Tomás. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Barila, Esteban Pablo. 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: Dye, Leandro. 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: Kovacs, Adrienn. University of Debrecen; Hungría
Fil: Bayasgalan, Tsogbadrakh. University of Debrecen; Hungría
Fil: Pal, Balazs. University of Debrecen; Hungría
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
XXXIV Reunión Anual SAN 2019
Villa Carlos Paz
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
NEURAL
CIRCUITS
BRAIN
KCNQ4
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:11336/195054
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/195054
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating systemStupniki, SofiaDionisio, Leonardo RaulPerotti, Gabriel TomásBarila, Esteban PabloDye, LeandroKovacs, AdriennBayasgalan, TsogbadrakhPal, BalazsSpitzmaul, Guillermo FedericoNEURALCIRCUITSBRAINKCNQ4https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The pedunculopontine nucleus (PPN) is part of the reticular activating system (RAS) which is associated with sleep regulation. The PPN has cholinergic and non-cholinergic neurons. A hallmark of the PPN-cholinergic neurons is the M-current, a slowly activating, non-inactivating voltage-gated potassium current. KCNQ2 to 5 subunit alone or in combination are responsible for the M-current. Our aim was to investigate the contribution of the KCNQ4 subunit to PPN neuronal function. We used a transgenic mouse model for KCNQ4 (knock-out (KO)) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). We analyzed KCNQ4 expression by real-time PCR and its localization using immunofluorescence. We also studied the M-current by electrophysiology on brain slices, the contribution of KCNQ4 to neuronal activity and its influence on circadian rhythm. We found a weak mRNA expression of KCNQ4 in PPN and the protein was located only on cholinergic neurons of the external limits of the nucleus. M-current was present in most of cholinergic neurons in WT animals, but absent in 40% of them in the KO ones. These last also exhibited behavioral alterations in the activity cycles showing a 5-hour increase and a higher sensitivity to changes in the light/darkness cycles. In summary, we found that only a subpopulation of PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm through the activity of the RAS system.Fil: Stupniki, Sofia. 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: Dionisio, Leonardo Raul. 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; ArgentinaFil: Perotti, Gabriel Tomás. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Barila, Esteban Pablo. 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: Dye, Leandro. 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: Kovacs, Adrienn. University of Debrecen; HungríaFil: Bayasgalan, Tsogbadrakh. University of Debrecen; HungríaFil: Pal, Balazs. University of Debrecen; HungríaFil: 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; ArgentinaXXXIV Reunión Anual SAN 2019Villa Carlos PazArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/195054Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system; XXXIV Reunión Anual SAN 2019; Villa Carlos Paz; Argentina; 2019; 139-140CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/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 Técnicas2025-10-15T14:49:03Zoai:ri.conicet.gov.ar:11336/195054instacron: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 14:49:04.037CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
title Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
spellingShingle Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
Stupniki, Sofia
NEURAL
CIRCUITS
BRAIN
KCNQ4
title_short Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
title_full Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
title_fullStr Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
title_full_unstemmed Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
title_sort Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system
dc.creator.none.fl_str_mv Stupniki, Sofia
Dionisio, Leonardo Raul
Perotti, Gabriel Tomás
Barila, Esteban Pablo
Dye, Leandro
Kovacs, Adrienn
Bayasgalan, Tsogbadrakh
Pal, Balazs
Spitzmaul, Guillermo Federico
author Stupniki, Sofia
author_facet Stupniki, Sofia
Dionisio, Leonardo Raul
Perotti, Gabriel Tomás
Barila, Esteban Pablo
Dye, Leandro
Kovacs, Adrienn
Bayasgalan, Tsogbadrakh
Pal, Balazs
Spitzmaul, Guillermo Federico
author_role author
author2 Dionisio, Leonardo Raul
Perotti, Gabriel Tomás
Barila, Esteban Pablo
Dye, Leandro
Kovacs, Adrienn
Bayasgalan, Tsogbadrakh
Pal, Balazs
Spitzmaul, Guillermo Federico
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NEURAL
CIRCUITS
BRAIN
KCNQ4
topic NEURAL
CIRCUITS
BRAIN
KCNQ4
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The pedunculopontine nucleus (PPN) is part of the reticular activating system (RAS) which is associated with sleep regulation. The PPN has cholinergic and non-cholinergic neurons. A hallmark of the PPN-cholinergic neurons is the M-current, a slowly activating, non-inactivating voltage-gated potassium current. KCNQ2 to 5 subunit alone or in combination are responsible for the M-current. Our aim was to investigate the contribution of the KCNQ4 subunit to PPN neuronal function. We used a transgenic mouse model for KCNQ4 (knock-out (KO)) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). We analyzed KCNQ4 expression by real-time PCR and its localization using immunofluorescence. We also studied the M-current by electrophysiology on brain slices, the contribution of KCNQ4 to neuronal activity and its influence on circadian rhythm. We found a weak mRNA expression of KCNQ4 in PPN and the protein was located only on cholinergic neurons of the external limits of the nucleus. M-current was present in most of cholinergic neurons in WT animals, but absent in 40% of them in the KO ones. These last also exhibited behavioral alterations in the activity cycles showing a 5-hour increase and a higher sensitivity to changes in the light/darkness cycles. In summary, we found that only a subpopulation of PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm through the activity of the RAS system.
Fil: Stupniki, Sofia. 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: Dionisio, Leonardo Raul. 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
Fil: Perotti, Gabriel Tomás. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Barila, Esteban Pablo. 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: Dye, Leandro. 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: Kovacs, Adrienn. University of Debrecen; Hungría
Fil: Bayasgalan, Tsogbadrakh. University of Debrecen; Hungría
Fil: Pal, Balazs. University of Debrecen; Hungría
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
XXXIV Reunión Anual SAN 2019
Villa Carlos Paz
Argentina
Sociedad Argentina de Investigación en Neurociencias
description The pedunculopontine nucleus (PPN) is part of the reticular activating system (RAS) which is associated with sleep regulation. The PPN has cholinergic and non-cholinergic neurons. A hallmark of the PPN-cholinergic neurons is the M-current, a slowly activating, non-inactivating voltage-gated potassium current. KCNQ2 to 5 subunit alone or in combination are responsible for the M-current. Our aim was to investigate the contribution of the KCNQ4 subunit to PPN neuronal function. We used a transgenic mouse model for KCNQ4 (knock-out (KO)) and one with fluorescent-labeled cholinergic neurons (tdTomatoStop+ChAT::Cre). We analyzed KCNQ4 expression by real-time PCR and its localization using immunofluorescence. We also studied the M-current by electrophysiology on brain slices, the contribution of KCNQ4 to neuronal activity and its influence on circadian rhythm. We found a weak mRNA expression of KCNQ4 in PPN and the protein was located only on cholinergic neurons of the external limits of the nucleus. M-current was present in most of cholinergic neurons in WT animals, but absent in 40% of them in the KO ones. These last also exhibited behavioral alterations in the activity cycles showing a 5-hour increase and a higher sensitivity to changes in the light/darkness cycles. In summary, we found that only a subpopulation of PPN cholinergic neurons have KCNQ4-dependent M-current and this subunit contributes to modulate the circadian rhythm through the activity of the RAS system.
publishDate 2019
dc.date.none.fl_str_mv 2019
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/11336/195054
Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system; XXXIV Reunión Anual SAN 2019; Villa Carlos Paz; Argentina; 2019; 139-140
CONICET Digital
CONICET
url http://hdl.handle.net/11336/195054
identifier_str_mv Physiological significance of the KCNQ4-mediated M-current in the pedunculopontine nucleus of the reticular activating system; XXXIV Reunión Anual SAN 2019; Villa Carlos Paz; Argentina; 2019; 139-140
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/
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
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
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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score 13.22299

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