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Title: M2 Cortex-Dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington's Disease
Author: Fernández García, Sara
Conde-Berriozábal, Sara
García, Esther
Gort Paniello, Clara
Bernal Casas, David
García-Díaz Barriga, Gerardo
López Gil, Xavier
Muñoz-Moreno, Emma
Soria, Guadalupe
Campa, Leticia
Artigas Pérez, Francesc
Rodríguez Allué, Manuel José
Alberch i Vié, Jordi
Masana Nadal, Mercè
Keywords: Corea de Huntington
Escorça cerebral
Models animals en la investigació
Huntington's chorea
Cerebral cortex
Animal models in research
Issue Date: 5-Oct-2020
Publisher: eLife Sciences
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.
Note: Reproducció del document publicat a:
It is part of: eLife, 2020, vol. 9, num. e57017
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ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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