Altered M2 Cortex - Superior Colliculus visual perception circuit in Huntington’s Disease
Altered M2 Cortex - Superior Colliculus visual perception circuit in Huntington’s Disease
Abstract The premotor cortical area -M2 cortex in rodents- connection to the striatum is involved in movement and prominently affected in Huntington’s Disease (HD). M2 cortex also projects to the superior colliculus (SC), implicated in oculomotor functions (i.e. saccades) and visual perception. Here, we investigated the contribution of M2 cortex – SC circuit to HD physiopathology in male mice. Using fMRI, we observed that M2 cortex functional connectivity with the SC was the most prominently affected circuit in the symptomatic R6/1 HD mouse model. Structural alterations were also detected by tractography and viral tracing. HD mice showed decreased defensive behavioral responses towards an unexpected visual stimuli, such as a moving robo-beetle, and decreased locomotion upon unexpected flash of light. Additionally, optogenetic M2 cortex – SC stimulation promoted avoidance responses towards the robo-beetle in WT, but not HD mice. Though, DWI measurements in vivo and ex vivo electrophysiological responses to optogenetic and electrical stimuli in the SC suggested preserved brain structure. Finally, GCamp6f fluorescence recordings with fiber photometry indicated that aberrant M2 cortex engagement might be the underlying mechanism of visual perception alterations in HD. Collectively, our findings point to a key role of M2 cortex - SC circuit alterations in HD pathophysiology.
Garc¨aa-Garc¨aa Esther、L¨?pez-Gil Javier、Soria Guadalupe、Garc¨aa-Gilabert Lia、Conde-Berriozabal Sara、Masana Merc¨¨、Rodr¨aguez Manuel J、Alberch Jordi、Boudjadja Mehdi Boutagouga、Mu?oz-Moreno Emma、Sitj¨¤-Roqueta Laia
Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Magnetic Resonance Imaging Core Facility, Institut d?ˉInvestigacions August Pi i Sunyer (IDIBAPS)Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Magnetic Resonance Imaging Core Facility, Institut d?ˉInvestigacions August Pi i Sunyer (IDIBAPS)||Laboratory of Surgical Neuroanatomy, Institute of Neurosciences, School of Medicine and Health Sciences, Universitat de Barcelona||Consorcio Centro de Investigaci¨?n Biom¨|dica en Red (CIBER) de Bioingenier¨aa, Biomateriales y Nanomedicina (CIBER-BBN)Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Metofico ltdInstitut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Magnetic Resonance Imaging Core Facility, Institut d?ˉInvestigacions August Pi i Sunyer (IDIBAPS)Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, University of Barcelona||Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
基础医学神经病学、精神病学生理学
Garc¨aa-Garc¨aa Esther,L¨?pez-Gil Javier,Soria Guadalupe,Garc¨aa-Gilabert Lia,Conde-Berriozabal Sara,Masana Merc¨¨,Rodr¨aguez Manuel J,Alberch Jordi,Boudjadja Mehdi Boutagouga,Mu?oz-Moreno Emma,Sitj¨¤-Roqueta Laia.Altered M2 Cortex - Superior Colliculus visual perception circuit in Huntington’s Disease[EB/OL].(2025-03-28)[2025-04-28].https://www.biorxiv.org/content/10.1101/2022.03.24.485610.点此复制
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