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http://hdl.handle.net/2445/201942
Title: | M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus |
Author: | 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 Masana Nadal, Mercè |
Keywords: | Malalties neurodegeneratives Corea de Huntington Neurodegenerative Diseases Huntington's chorea |
Issue Date: | 3-May-2023 |
Publisher: | The Society for Neuroscience |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1523/JNEUROSCI.1172-22.2023 |
It is part of: | Journal of Neuroscience, 2023, vol. 18, num. 43, p. 3379-3390 |
URI: | http://hdl.handle.net/2445/201942 |
Related resource: | https://doi.org/10.1523/JNEUROSCI.1172-22.2023 |
ISSN: | 0270-6474 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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