Open Collections

Trappenberg, Kai

University of British Columbia

Huntington’s disease (HD) is a neurodegenerative disorder that affects numerous brain functions, yet how altered sensory processing contributes to behavioural and learning deficits remains poorly understood. Previous wide-field mesoscale imaging and electrophysiological recordings from anesthetized HD model mice revealed that sensory stimulation induced widespread, and prolonged cortical activity in more brain regions compared to wildtype (WT) littermates. Further imaging of awake mice produced similar results, suggesting that HD disrupts the sensory processing networks of visual stimuli. Building on these findings, this project aimed to investigate the behavioural relevance of sensory spread by designing a custom Raspberry Pi-controlled two-alternative forced choice (2AFC) rig. Through multiple iterations, a reliable system was developed that enabled head-fixed zQ175 knock-in HD mice and WT controls crossed with Thy1-GCaMP6s mice, to perform a visual discrimination task while mesoscale calcium imaging recorded activity across layer 2/3 of the cortex. Mice that successfully licked the reward spout displayed decreased global cortical activity before the reward presentation, with WT mice showing more spatially localized suppression than HD mice. HD mice exhibited exaggerated cortical responses to visual stimuli and prolonged motor-related activity during licking. However, both HD and WT mice struggled to consistently associate single and double flash stimuli with the correct motor response, highlighting the challenge of linking altered cortical dynamics to behaviour. While technical challenges and limited sample sizes prevented definitive genotype-based comparisons, the custom behavioural system lays the groundwork for future studies on how sensory processing deficits contribute to cognitive impairments in HD. This work provides an important step toward understanding the interplay between cortical circuit dysfunction and behavioural outcomes in HD, offering a novel platform to investigate early sensory learning impairments.

Text

2025-04-14

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/90645

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/