Fernández-García, SaraConde-Berriozabal, SaraGarcía-García, EstherGort-Paniello, ClaraBernal-Casas, DavidGarcía-Díaz Barriga, GerardoLópez-Gil, XavierMuñoz-Moreno, EmmaSoria Rodríguez, GuadalupeCampa, LeticiaArtigas, FrancescRodríguez, Manuel JoséAlberch, JordiMasana, Mercè2025-11-242025-11-242020Fernández-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.570172050-084Xhttp://hdl.handle.net/10230/71978Huntington’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.application/pdfeng© 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.Corea de Huntington (Malaltia)NeurociènciaGanglis basalsM2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s diseaseinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.7554/eLife.57017info:eu-repo/semantics/openAccess