Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.

Background. Network alterations underlying neurodegenerative diseases often precede symptoms and functional deficits. Thus, their early identification is central for improved prognosis. In Huntington's disease (HD), the cortico-striatal networks, involved in motor function processing, are the m...

Descripción completa

Detalles Bibliográficos
Autores: Fernández, Sara (Fernández García), Orlandi, Javier G., García-Díaz Barriga, Gerardo, Rodríguez Allué, Manuel José, Masana Nadal, Mercè, Soriano i Fradera, Jordi, Alberch i Vié, Jordi, 1959-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171308
Acceso en línea:https://hdl.handle.net/2445/171308
Access Level:acceso abierto
Palabra clave:Corea de Huntington
Xarxes neuronals (Neurobiologia)
Huntington's chorea
Neural networks (Neurobiology)
id ES_b910b48b474c81ef3e536d12fcc6f4e1
oai_identifier_str oai:recercat.cat:2445/171308
network_acronym_str ES
network_name_str España
repository_id_str
spelling Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.Fernández, Sara (Fernández García)Orlandi, Javier G.García-Díaz Barriga, GerardoRodríguez Allué, Manuel JoséMasana Nadal, MercèSoriano i Fradera, JordiAlberch i Vié, Jordi, 1959-Corea de HuntingtonXarxes neuronals (Neurobiologia)Huntington's choreaNeural networks (Neurobiology)Background. Network alterations underlying neurodegenerative diseases often precede symptoms and functional deficits. Thus, their early identification is central for improved prognosis. In Huntington's disease (HD), the cortico-striatal networks, involved in motor function processing, are the most compromised neural substrate. However, whether the network alterations are intrinsic of the striatum or the cortex is not fully understood. Results In order to identify early HD neural deficits, we characterized neuronal ensemble calcium activity and network topology of HD striatal and cortical cultures. We used large-scale calcium imaging combined with activity-based network inference analysis. We extracted collective activity events and inferred the topology of the neuronal network in cortical and striatal primary cultures from wild-type and R6/1 mouse model of HD. Striatal, but not cortical, HD networks displayed lower activity and a lessened ability to integrate information. GABAA receptor blockade in healthy and HD striatal cultures generated similar coordinated ensemble activity and network topology, highlighting that the excitatory component of striatal system is spared in HD. Conversely, NMDA receptor activation increased individual neuronal activity while coordinated activity became highly variable and undefined. Interestingly, by boosting NMDA activity, we rectified striatal HD network alterations. Conclusions. Overall, our integrative approach highlights striatal defective network integration capacity as a major contributor of basal ganglia dysfunction in HD and suggests that increased excitatory drive may serve as a potential intervention. In addition, our work provides a valuable tool to evaluate in vitro network recovery after treatment intervention in basal ganglia disorders.BioMed Central2020202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/171308Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s12915-020-00794-4Bmc Biology, 2020, vol. 18, p. 58https://doi.org/10.1186/s12915-020-00794-4info:eu-repo/grantAgreement/EC/H2020/863214info:eu-repo/grantAgreement/EC/H2020/713140cc-by (c) Fernández García, Sara et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1713082026-05-29T05:05:01Z
dc.title.none.fl_str_mv Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
title Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
spellingShingle Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
Fernández, Sara (Fernández García)
Corea de Huntington
Xarxes neuronals (Neurobiologia)
Huntington's chorea
Neural networks (Neurobiology)
title_short Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
title_full Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
title_fullStr Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
title_full_unstemmed Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
title_sort Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
dc.creator.none.fl_str_mv Fernández, Sara (Fernández García)
Orlandi, Javier G.
García-Díaz Barriga, Gerardo
Rodríguez Allué, Manuel José
Masana Nadal, Mercè
Soriano i Fradera, Jordi
Alberch i Vié, Jordi, 1959-
author Fernández, Sara (Fernández García)
author_facet Fernández, Sara (Fernández García)
Orlandi, Javier G.
García-Díaz Barriga, Gerardo
Rodríguez Allué, Manuel José
Masana Nadal, Mercè
Soriano i Fradera, Jordi
Alberch i Vié, Jordi, 1959-
author_role author
author2 Orlandi, Javier G.
García-Díaz Barriga, Gerardo
Rodríguez Allué, Manuel José
Masana Nadal, Mercè
Soriano i Fradera, Jordi
Alberch i Vié, Jordi, 1959-
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Corea de Huntington
Xarxes neuronals (Neurobiologia)
Huntington's chorea
Neural networks (Neurobiology)
topic Corea de Huntington
Xarxes neuronals (Neurobiologia)
Huntington's chorea
Neural networks (Neurobiology)
description Background. Network alterations underlying neurodegenerative diseases often precede symptoms and functional deficits. Thus, their early identification is central for improved prognosis. In Huntington's disease (HD), the cortico-striatal networks, involved in motor function processing, are the most compromised neural substrate. However, whether the network alterations are intrinsic of the striatum or the cortex is not fully understood. Results In order to identify early HD neural deficits, we characterized neuronal ensemble calcium activity and network topology of HD striatal and cortical cultures. We used large-scale calcium imaging combined with activity-based network inference analysis. We extracted collective activity events and inferred the topology of the neuronal network in cortical and striatal primary cultures from wild-type and R6/1 mouse model of HD. Striatal, but not cortical, HD networks displayed lower activity and a lessened ability to integrate information. GABAA receptor blockade in healthy and HD striatal cultures generated similar coordinated ensemble activity and network topology, highlighting that the excitatory component of striatal system is spared in HD. Conversely, NMDA receptor activation increased individual neuronal activity while coordinated activity became highly variable and undefined. Interestingly, by boosting NMDA activity, we rectified striatal HD network alterations. Conclusions. Overall, our integrative approach highlights striatal defective network integration capacity as a major contributor of basal ganglia dysfunction in HD and suggests that increased excitatory drive may serve as a potential intervention. In addition, our work provides a valuable tool to evaluate in vitro network recovery after treatment intervention in basal ganglia disorders.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/171308
url https://hdl.handle.net/2445/171308
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12915-020-00794-4
Bmc Biology, 2020, vol. 18, p. 58
https://doi.org/10.1186/s12915-020-00794-4
info:eu-repo/grantAgreement/EC/H2020/863214
info:eu-repo/grantAgreement/EC/H2020/713140
dc.rights.none.fl_str_mv cc-by (c) Fernández García, Sara et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Fernández García, Sara et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417721630818304
score 15,81155

Similares en LA Referencia