M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus

• DOI: 10.1523/jneurosci.1172-22.2023
• Publication Date: 2023-03-31T17:50:44Z
• Authors: Sara Conde-Berrio...; Lia García-Gilabert; Esther García-García; Laia Sitjà-Roqueta; Xavier López-Gil; Emma Muñoz-Moreno; Mehdi Boutagouga ...; Guadalupe Soria; Manuel J Rodríguez; Jordi Alberch; Mercè Masana
• Keywords: Superior colliculus; Premotor cortex

Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex rodents, is the most affected cortical input to striatum from early stages patients associated motor learning deficits present HD mice. Yet, sends additional long-range axon collaterals diverse output brain regions beyond basal ganglia. Here, we aimed elucidate contribution of projections pathophysiology Using fMRI, showed prominent functional connectivity with superior colliculus (SC) symptomatic R6/1 male Structural were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure similar electrophysiological responses obtained on optogenetic stimulation axons. Male female mice behavioral linked function, including decreased defensive toward unexpected stimuli, such as a moving robo-beetle, locomotion an flash light. Additionally, GCamp6f fluorescence recordings fiber photometry that activity was engaged presence randomly robo-bettle, effect absent Moreover, acute chemogenetic inhibition WT shift phenotype. Collectively, our findings highlight involvement visual stimuli-induced responses, which are deeply altered mouse model. SIGNIFICANCE STATEMENT Understanding disorders critical for developing circuit-based therapeutic interventions. The prominently disturbed (HD); particularly, has role. However, same neurons send several striatum. We new structural circuitry models found projection impaired. describe differential sensory stimulus models, relies function. Our data SC-dependent processing its pathophysiology.