M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s disease
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- dc.contributor.author Fernández-García, Sara
- dc.contributor.author Conde-Berriozabal, Sara
- dc.contributor.author García-García, Esther
- dc.contributor.author Gort-Paniello, Clara
- dc.contributor.author Bernal-Casas, David
- dc.contributor.author García-Díaz Barriga, Gerardo
- dc.contributor.author López-Gil, Xavier
- dc.contributor.author Muñoz-Moreno, Emma
- dc.contributor.author Soria Rodríguez, Guadalupe
- dc.contributor.author Campa, Leticia
- dc.contributor.author Artigas, Francesc
- dc.contributor.author Rodríguez, Manuel José
- dc.contributor.author Alberch, Jordi
- dc.contributor.author Masana, Mercè
- dc.date.accessioned 2025-11-24T07:06:58Z
- dc.date.available 2025-11-24T07:06:58Z
- dc.date.issued 2020
- dc.description.abstract Huntington’s disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of the basal ganglia. The cerebral cortex is the main striatal afferent, and progressive cortico-striatal disconnection characterizes HD. We mapped striatal network dysfunction in HD mice to ultimately modulate the activity of a specific cortico-striatal circuit to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRI in vivo indicates cortico-striatal and thalamo-striatal functional network deficits and reduced glutamate/glutamine ratio in the striatum of HD mice. Moreover, optogenetically-induced glutamate release from M2 cortex terminals in the dorsolateral striatum (DLS) was undetectable in HD mice and striatal neurons show blunted electrophysiological responses. Remarkably, repeated M2-DLS optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that selective stimulation of the M2-DLS pathway can become an effective therapeutic strategy in HD.en
- dc.description.sponsorship We are very grateful to Ana López (María de Maeztu Unit of Excellence, Institute of Neurosciences, University of Barcelona, MDM-2017–0729, Ministry of Science, Innovation, and Universities) and Maite Muñoz for their excellent technical support. This work has been funded by the Spanish Ministry of Sciences, Innovation and Universities through projects no. SAF2017-88076-R, RETICS de Terapia Celular, Instituto de Salud Carlos III (RD06/0010/0006), and la Marató de TV3. This research is part of NEUROPA. The NEUROPA Project has received funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 863214.en
- dc.format.mimetype application/pdf
- dc.identifier.citation Fernández-García S, Conde-Berriozabal S, García-García E, Gort-Paniello C, Bernal-Casas D, García-Díaz Barriga G, et al. M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s disease. Elife. 2020;9:e57017. DOI: 10.7554/eLife.57017
- dc.identifier.doi http://dx.doi.org/10.7554/eLife.57017
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/71978
- dc.language.iso eng
- dc.publisher eLife
- dc.relation.ispartof Elife. 2020;9:e57017
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/863214
- dc.rights © Copyright Fernández-García et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Corea de Huntington (Malaltia)ca
- dc.subject.other Neurociènciaca
- dc.subject.other Ganglis basalsca
- dc.title M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s diseaseen
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion