2026-04-13T02:09:26Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/719782025-11-26T06:04:46Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Fernández-García, Sara author Conde-Berriozabal, Sara author García-García, Esther author Gort-Paniello, Clara author Bernal-Casas, David author García-Díaz Barriga, Gerardo author López-Gil, Xavier author Muñoz-Moreno, Emma author Soria Rodríguez, Guadalupe author Campa, Leticia author Artigas, Francesc author Rodríguez, Manuel José author Alberch, Jordi author Masana, Mercè author 2025-11-24T07:06:58Z 2025-11-24T07:06:58Z 2020 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. 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. http://hdl.handle.net/10230/71978 Corea de Huntington (Malaltia) Neurociència Ganglis basals M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s disease