Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia

Autores
Aïssa, Hind Baba; Sala, Romain W.; Georgescu Margarint, Elena Laura; Frontera, Jimena Laura; Varani, Andrés Pablo; Menardy, Fabien; Pelosi, Assunta; Hervé, Denis; Léna, Clément; Popa, Daniela
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/−) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.
Fil: Aïssa, Hind Baba. Ecole Normale Supérieure; Francia
Fil: Sala, Romain W.. Ecole Normale Supérieure; Francia
Fil: Georgescu Margarint, Elena Laura. Ecole Normale Supérieure; Francia
Fil: Frontera, Jimena Laura. Ecole Normale Supérieure; Francia
Fil: Varani, Andrés Pablo. Ecole Normale Supérieure; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Menardy, Fabien. Ecole Normale Supérieure; Francia
Fil: Pelosi, Assunta. Inserm; Francia. Université Pierre et Marie Curie; Francia
Fil: Hervé, Denis. Université Pierre et Marie Curie; Francia. Inserm; Francia. Institut Du Fer À Moulin; Francia
Fil: Léna, Clément. Ecole Normale Supérieure; Francia
Fil: Popa, Daniela. Ecole Normale Supérieure; Francia
Materia
GNAL
CEREBELLUM
DYSTONIA
ELECTROPHYSIOLOGY
MOTOR CORTEX
MOUSE
NEUROSCIENCE
THALAMUS
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:11336/203522
Acceder
id CONICETDig_2afc3b1d49938f15f3f7378a4a6dca57
oai_identifier_str oai:ri.conicet.gov.ar:11336/203522
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystoniaAïssa, Hind BabaSala, Romain W.Georgescu Margarint, Elena LauraFrontera, Jimena LauraVarani, Andrés PabloMenardy, FabienPelosi, AssuntaHervé, DenisLéna, ClémentPopa, DanielaGNALCEREBELLUMDYSTONIAELECTROPHYSIOLOGYMOTOR CORTEXMOUSENEUROSCIENCETHALAMUShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/−) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.Fil: Aïssa, Hind Baba. Ecole Normale Supérieure; FranciaFil: Sala, Romain W.. Ecole Normale Supérieure; FranciaFil: Georgescu Margarint, Elena Laura. Ecole Normale Supérieure; FranciaFil: Frontera, Jimena Laura. Ecole Normale Supérieure; FranciaFil: Varani, Andrés Pablo. Ecole Normale Supérieure; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Menardy, Fabien. Ecole Normale Supérieure; FranciaFil: Pelosi, Assunta. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Hervé, Denis. Université Pierre et Marie Curie; Francia. Inserm; Francia. Institut Du Fer À Moulin; FranciaFil: Léna, Clément. Ecole Normale Supérieure; FranciaFil: Popa, Daniela. Ecole Normale Supérieure; FranciaeLife Sciences2022-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/203522Aïssa, Hind Baba; Sala, Romain W.; Georgescu Margarint, Elena Laura; Frontera, Jimena Laura; Varani, Andrés Pablo; et al.; Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia; eLife Sciences; eLife; 11; 6-2022; 1-242050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.79135info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/79135info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:14Zoai:ri.conicet.gov.ar:11336/203522instacron: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:34982025-09-03 09:52:14.595CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
title Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
spellingShingle Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
Aïssa, Hind Baba
GNAL
CEREBELLUM
DYSTONIA
ELECTROPHYSIOLOGY
MOTOR CORTEX
MOUSE
NEUROSCIENCE
THALAMUS
title_short Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
title_full Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
title_fullStr Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
title_full_unstemmed Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
title_sort Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia
dc.creator.none.fl_str_mv Aïssa, Hind Baba
Sala, Romain W.
Georgescu Margarint, Elena Laura
Frontera, Jimena Laura
Varani, Andrés Pablo
Menardy, Fabien
Pelosi, Assunta
Hervé, Denis
Léna, Clément
Popa, Daniela
author Aïssa, Hind Baba
author_facet Aïssa, Hind Baba
Sala, Romain W.
Georgescu Margarint, Elena Laura
Frontera, Jimena Laura
Varani, Andrés Pablo
Menardy, Fabien
Pelosi, Assunta
Hervé, Denis
Léna, Clément
Popa, Daniela
author_role author
author2 Sala, Romain W.
Georgescu Margarint, Elena Laura
Frontera, Jimena Laura
Varani, Andrés Pablo
Menardy, Fabien
Pelosi, Assunta
Hervé, Denis
Léna, Clément
Popa, Daniela
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GNAL
CEREBELLUM
DYSTONIA
ELECTROPHYSIOLOGY
MOTOR CORTEX
MOUSE
NEUROSCIENCE
THALAMUS
topic GNAL
CEREBELLUM
DYSTONIA
ELECTROPHYSIOLOGY
MOTOR CORTEX
MOUSE
NEUROSCIENCE
THALAMUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/−) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.
Fil: Aïssa, Hind Baba. Ecole Normale Supérieure; Francia
Fil: Sala, Romain W.. Ecole Normale Supérieure; Francia
Fil: Georgescu Margarint, Elena Laura. Ecole Normale Supérieure; Francia
Fil: Frontera, Jimena Laura. Ecole Normale Supérieure; Francia
Fil: Varani, Andrés Pablo. Ecole Normale Supérieure; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Menardy, Fabien. Ecole Normale Supérieure; Francia
Fil: Pelosi, Assunta. Inserm; Francia. Université Pierre et Marie Curie; Francia
Fil: Hervé, Denis. Université Pierre et Marie Curie; Francia. Inserm; Francia. Institut Du Fer À Moulin; Francia
Fil: Léna, Clément. Ecole Normale Supérieure; Francia
Fil: Popa, Daniela. Ecole Normale Supérieure; Francia
description Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/−) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.
publishDate 2022
dc.date.none.fl_str_mv 2022-06
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/11336/203522
Aïssa, Hind Baba; Sala, Romain W.; Georgescu Margarint, Elena Laura; Frontera, Jimena Laura; Varani, Andrés Pablo; et al.; Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia; eLife Sciences; eLife; 11; 6-2022; 1-24
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/203522
identifier_str_mv Aïssa, Hind Baba; Sala, Romain W.; Georgescu Margarint, Elena Laura; Frontera, Jimena Laura; Varani, Andrés Pablo; et al.; Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia; eLife Sciences; eLife; 11; 6-2022; 1-24
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.79135
info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/79135
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
dc.publisher.none.fl_str_mv eLife Sciences
publisher.none.fl_str_mv eLife 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_ 1842269145463259136
score 13.13397

Publicaciones similares