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Títol: M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus
Autor: Conde-Berriozábal, Sara
García Gilabert, Lia
García García, Esther
Sitjà Roqueta, Laia
López Gil, Xavier
Muñoz-Moreno, Emma
Boutagouga Boudjadja, Mehdi
Soria, Guadalupe
Rodríguez Allué, Manuel José
Alberch i Vié, Jordi, 1959-
Masana Nadal, Mercè
Matèria: Malalties neurodegeneratives
Corea de Huntington
Neurodegenerative Diseases
Huntington's chorea
Data de publicació: 3-maig-2023
Publicat per: The Society for Neuroscience
Resum: Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learning deficits present in HD mice. Yet, M2 cortex sends additional long-range axon collaterals to diverse output brain regions beyond basal ganglia. Here, we aimed to elucidate the contribution of M2 cortex projections to HD pathophysiology in mice. Using fMRI, M2 cortex showed most prominent functional connectivity alterations with the superior colliculus (SC) in symptomatic R6/1 HD male mice. Structural alterations were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure and similar electrophysiological responses were obtained in the SC on optogenetic stimulation of M2 cortical axons. Male and female HD mice showed behavioral alterations linked to SC function, including decreased defensive behavioral responses toward unexpected stimuli, such as a moving robo-beetle, and decreased locomotion on an unexpected flash of light. Additionally, GCamp6f fluorescence recordings with fiber photometry showed that M2 cortex activity was engaged by the presence of a randomly moving robo-bettle, an effect absent in HD male mice. Moreover, acute chemogenetic M2 cortex inhibition in WT mice shift behavioral responses toward an HD phenotype. Collectively, our findings highlight the involvement of M2 cortex activity in visual stimuli-induced behavioral responses, which are deeply altered in the R6/1 HD mouse model.
Nota: Reproducció del document publicat a: https://doi.org/10.1523/JNEUROSCI.1172-22.2023
És part de: Journal of Neuroscience, 2023, vol. 18, num. 43, p. 3379-3390
URI: https://hdl.handle.net/2445/201942
Recurs relacionat: https://doi.org/10.1523/JNEUROSCI.1172-22.2023
ISSN: 0270-6474
Apareix en les col·leccions:Articles publicats en revistes (Biomedicina)

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