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2020-10-05

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cc-by (c) Fernández García, Sara et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171293

M2 Cortex-Dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington's Disease

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https://doi.org/10.7554/eLife.57017

Resum

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.

Matèries

Corea de Huntington, Escorça cerebral, Models animals en la investigació

Matèries (anglès)

Huntington's chorea, Cerebral cortex, Animal models in research

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

FERNÁNDEZ, Sara (fernández garcía), CONDE-BERRIOZÁBAL, Sara, GARCÍA-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. M2 Cortex-Dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington's Disease. _eLife_. 2020. Vol. 9, núm. e57017. [consulta: 24 de gener de 2026]. ISSN: 2050-084X. [Disponible a: https://hdl.handle.net/2445/171293]

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