M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus

Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learnin...

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Autores: Conde-Berriozábal, Sara, García Gilabert, Lia, García-García, Esther, Sitjà Roqueta, Laia, López Gil, Xavier, Muñoz-Moreno, Emma, Boutagouga Boudjadja, Mehdi, Soria, Guadalupe, Rodríguez Allué, Manuel José, Alberch i Vié, Jordi, 1959-, Masana Nadal, Mercè
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
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:2445/201942
Acceso en línea:https://hdl.handle.net/2445/201942
Access Level:acceso abierto
Palabra clave:Malalties neurodegeneratives
Corea de Huntington
Neurodegenerative Diseases
Huntington's chorea
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spelling M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior ColliculusConde-Berriozábal, SaraGarcía Gilabert, LiaGarcía-García, EstherSitjà Roqueta, LaiaLópez Gil, XavierMuñoz-Moreno, EmmaBoutagouga Boudjadja, MehdiSoria, GuadalupeRodríguez Allué, Manuel JoséAlberch i Vié, Jordi, 1959-Masana Nadal, MercèMalalties neurodegenerativesCorea de HuntingtonNeurodegenerative DiseasesHuntington's choreaEarly and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learning deficits present in HD mice. Yet, M2 cortex sends additional long-range axon collaterals to diverse output brain regions beyond basal ganglia. Here, we aimed to elucidate the contribution of M2 cortex projections to HD pathophysiology in mice. Using fMRI, M2 cortex showed most prominent functional connectivity alterations with the superior colliculus (SC) in symptomatic R6/1 HD male mice. Structural alterations were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure and similar electrophysiological responses were obtained in the SC on optogenetic stimulation of M2 cortical axons. Male and female HD mice showed behavioral alterations linked to SC function, including decreased defensive behavioral responses toward unexpected stimuli, such as a moving robo-beetle, and decreased locomotion on an unexpected flash of light. Additionally, GCamp6f fluorescence recordings with fiber photometry showed that M2 cortex activity was engaged by the presence of a randomly moving robo-bettle, an effect absent in HD male mice. Moreover, acute chemogenetic M2 cortex inhibition in WT mice shift behavioral responses toward an HD phenotype. Collectively, our findings highlight the involvement of M2 cortex activity in visual stimuli-induced behavioral responses, which are deeply altered in the R6/1 HD mouse model.The Society for Neuroscience2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/201942Articles 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/10.1523/JNEUROSCI.1172-22.2023Journal of Neuroscience, 2023, vol. 18, num. 43, p. 3379-3390https://doi.org/10.1523/JNEUROSCI.1172-22.2023cc-by-nc-sa (c) Conde-Berriozábal, Sara et al., 2023https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2019422026-05-29T05:05:01Z
dc.title.none.fl_str_mv M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
title M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
spellingShingle M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
Conde-Berriozábal, Sara
Malalties neurodegeneratives
Corea de Huntington
Neurodegenerative Diseases
Huntington's chorea
title_short M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
title_full M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
title_fullStr M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
title_full_unstemmed M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
title_sort M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
dc.creator.none.fl_str_mv Conde-Berriozábal, Sara
García Gilabert, Lia
García-García, Esther
Sitjà Roqueta, Laia
López Gil, Xavier
Muñoz-Moreno, Emma
Boutagouga Boudjadja, Mehdi
Soria, Guadalupe
Rodríguez Allué, Manuel José
Alberch i Vié, Jordi, 1959-
Masana Nadal, Mercè
author Conde-Berriozábal, Sara
author_facet Conde-Berriozábal, Sara
García Gilabert, Lia
García-García, Esther
Sitjà Roqueta, Laia
López Gil, Xavier
Muñoz-Moreno, Emma
Boutagouga Boudjadja, Mehdi
Soria, Guadalupe
Rodríguez Allué, Manuel José
Alberch i Vié, Jordi, 1959-
Masana Nadal, Mercè
author_role author
author2 García Gilabert, Lia
García-García, Esther
Sitjà Roqueta, Laia
López Gil, Xavier
Muñoz-Moreno, Emma
Boutagouga Boudjadja, Mehdi
Soria, Guadalupe
Rodríguez Allué, Manuel José
Alberch i Vié, Jordi, 1959-
Masana Nadal, Mercè
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties neurodegeneratives
Corea de Huntington
Neurodegenerative Diseases
Huntington's chorea
topic Malalties neurodegeneratives
Corea de Huntington
Neurodegenerative Diseases
Huntington's chorea
description Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learning deficits present in HD mice. Yet, M2 cortex sends additional long-range axon collaterals to diverse output brain regions beyond basal ganglia. Here, we aimed to elucidate the contribution of M2 cortex projections to HD pathophysiology in mice. Using fMRI, M2 cortex showed most prominent functional connectivity alterations with the superior colliculus (SC) in symptomatic R6/1 HD male mice. Structural alterations were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure and similar electrophysiological responses were obtained in the SC on optogenetic stimulation of M2 cortical axons. Male and female HD mice showed behavioral alterations linked to SC function, including decreased defensive behavioral responses toward unexpected stimuli, such as a moving robo-beetle, and decreased locomotion on an unexpected flash of light. Additionally, GCamp6f fluorescence recordings with fiber photometry showed that M2 cortex activity was engaged by the presence of a randomly moving robo-bettle, an effect absent in HD male mice. Moreover, acute chemogenetic M2 cortex inhibition in WT mice shift behavioral responses toward an HD phenotype. Collectively, our findings highlight the involvement of M2 cortex activity in visual stimuli-induced behavioral responses, which are deeply altered in the R6/1 HD mouse model.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
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/2445/201942
url https://hdl.handle.net/2445/201942
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/10.1523/JNEUROSCI.1172-22.2023
Journal of Neuroscience, 2023, vol. 18, num. 43, p. 3379-3390
https://doi.org/10.1523/JNEUROSCI.1172-22.2023
dc.rights.none.fl_str_mv cc-by-nc-sa (c) Conde-Berriozábal, Sara et al., 2023
https://creativecommons.org/licenses/by-nc-sa/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-sa (c) Conde-Berriozábal, Sara et al., 2023
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv The Society for Neuroscience
publisher.none.fl_str_mv The Society for Neuroscience
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
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score 15,81155

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