Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms

Autores
Bussi, Ivana Leda; Neitz, Alexandra F.; Sanchez, Raymond E A; Casiraghi, Leandro Pablo; Moldavan, Michael; Kunda, Divya; Allen, Charles N.; Evans, Jennifer A.; de la Iglesia, Horacio Oscar
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter Vgat from neuromedin-S (NMS)+ neurons-a subset of neurons critical for SCN function-causes arrhythmia of locomotor activity and sleep. Further, NMS-Vgat deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function, Vgat deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of Vgat led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker's ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker.
Fil: Bussi, Ivana Leda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Washington; Estados Unidos
Fil: Neitz, Alexandra F.. University of Washington; Estados Unidos
Fil: Sanchez, Raymond E A. University of Washington; Estados Unidos
Fil: Casiraghi, Leandro Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés. Escuela de Educación; Argentina. University of Washington; Estados Unidos
Fil: Moldavan, Michael. Oregon Health And Science University; Estados Unidos
Fil: Kunda, Divya. University of Washington; Estados Unidos
Fil: Allen, Charles N.. Oregon Health And Science University; Estados Unidos
Fil: Evans, Jennifer A.. Marquette University; Estados Unidos
Fil: de la Iglesia, Horacio Oscar. University of Washington; Estados Unidos
Materia
GABA
SLEEP
SUPRACHIASMATIC
VGAT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/220535
Acceder
id CONICETDig_6484b0dfcc29169ff440088d84d5084f
oai_identifier_str oai:ri.conicet.gov.ar:11336/220535
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythmsBussi, Ivana LedaNeitz, Alexandra F.Sanchez, Raymond E ACasiraghi, Leandro PabloMoldavan, MichaelKunda, DivyaAllen, Charles N.Evans, Jennifer A.de la Iglesia, Horacio OscarGABASLEEPSUPRACHIASMATICVGAThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter Vgat from neuromedin-S (NMS)+ neurons-a subset of neurons critical for SCN function-causes arrhythmia of locomotor activity and sleep. Further, NMS-Vgat deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function, Vgat deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of Vgat led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker's ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker.Fil: Bussi, Ivana Leda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Washington; Estados UnidosFil: Neitz, Alexandra F.. University of Washington; Estados UnidosFil: Sanchez, Raymond E A. University of Washington; Estados UnidosFil: Casiraghi, Leandro Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés. Escuela de Educación; Argentina. University of Washington; Estados UnidosFil: Moldavan, Michael. Oregon Health And Science University; Estados UnidosFil: Kunda, Divya. University of Washington; Estados UnidosFil: Allen, Charles N.. Oregon Health And Science University; Estados UnidosFil: Evans, Jennifer A.. Marquette University; Estados UnidosFil: de la Iglesia, Horacio Oscar. University of Washington; Estados UnidosNational Academy of Sciences2023-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/220535Bussi, Ivana Leda; Neitz, Alexandra F.; Sanchez, Raymond E A; Casiraghi, Leandro Pablo; Moldavan, Michael; et al.; Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 120; 49; 12-2023; 1-100027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pnas.org/doi/10.1073/pnas.2314857120info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2314857120info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:11:08Zoai:ri.conicet.gov.ar:11336/220535instacron: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:34982025-10-22 12:11:09.192CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
title Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
spellingShingle Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
Bussi, Ivana Leda
GABA
SLEEP
SUPRACHIASMATIC
VGAT
title_short Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
title_full Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
title_fullStr Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
title_full_unstemmed Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
title_sort Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms
dc.creator.none.fl_str_mv Bussi, Ivana Leda
Neitz, Alexandra F.
Sanchez, Raymond E A
Casiraghi, Leandro Pablo
Moldavan, Michael
Kunda, Divya
Allen, Charles N.
Evans, Jennifer A.
de la Iglesia, Horacio Oscar
author Bussi, Ivana Leda
author_facet Bussi, Ivana Leda
Neitz, Alexandra F.
Sanchez, Raymond E A
Casiraghi, Leandro Pablo
Moldavan, Michael
Kunda, Divya
Allen, Charles N.
Evans, Jennifer A.
de la Iglesia, Horacio Oscar
author_role author
author2 Neitz, Alexandra F.
Sanchez, Raymond E A
Casiraghi, Leandro Pablo
Moldavan, Michael
Kunda, Divya
Allen, Charles N.
Evans, Jennifer A.
de la Iglesia, Horacio Oscar
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GABA
SLEEP
SUPRACHIASMATIC
VGAT
topic GABA
SLEEP
SUPRACHIASMATIC
VGAT
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 suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter Vgat from neuromedin-S (NMS)+ neurons-a subset of neurons critical for SCN function-causes arrhythmia of locomotor activity and sleep. Further, NMS-Vgat deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function, Vgat deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of Vgat led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker's ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker.
Fil: Bussi, Ivana Leda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Washington; Estados Unidos
Fil: Neitz, Alexandra F.. University of Washington; Estados Unidos
Fil: Sanchez, Raymond E A. University of Washington; Estados Unidos
Fil: Casiraghi, Leandro Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés. Escuela de Educación; Argentina. University of Washington; Estados Unidos
Fil: Moldavan, Michael. Oregon Health And Science University; Estados Unidos
Fil: Kunda, Divya. University of Washington; Estados Unidos
Fil: Allen, Charles N.. Oregon Health And Science University; Estados Unidos
Fil: Evans, Jennifer A.. Marquette University; Estados Unidos
Fil: de la Iglesia, Horacio Oscar. University of Washington; Estados Unidos
description The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter Vgat from neuromedin-S (NMS)+ neurons-a subset of neurons critical for SCN function-causes arrhythmia of locomotor activity and sleep. Further, NMS-Vgat deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function, Vgat deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of Vgat led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker's ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker.
publishDate 2023
dc.date.none.fl_str_mv 2023-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/220535
Bussi, Ivana Leda; Neitz, Alexandra F.; Sanchez, Raymond E A; Casiraghi, Leandro Pablo; Moldavan, Michael; et al.; Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 120; 49; 12-2023; 1-10
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/220535
identifier_str_mv Bussi, Ivana Leda; Neitz, Alexandra F.; Sanchez, Raymond E A; Casiraghi, Leandro Pablo; Moldavan, Michael; et al.; Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 120; 49; 12-2023; 1-10
0027-8424
1091-6490
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://pnas.org/doi/10.1073/pnas.2314857120
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2314857120
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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
_version_ 1846782501577555968
score 12.982451

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