Investigating the neural basis of sensory learning in a mouse model of Huntington's disease : insights from mesoscale microscopy
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Trappenberg, Kai
issued: 2025-04-14T17:18:56Z
issued: 2025
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: 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 pl…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/90645
note: Investigating the Neural Basis ofSensory Learning in a Mouse Model ofHuntington’s DiseaseInsights from Mesoscale MicroscopybyKai TrappenbergB.Sc., Dalhousie University, 2022A THESIS SUBMITTED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFMASTER OF SCIENCEinThe Faculty of Graduate and Postdoctoral Studies(Neuroscience)THE UNIVERSITY OF BRITISH COLUMBIA(Vancouver)April, 2025© Kai Trappenberg 2025The following individuals certify that they have read, and recommend to the Faculty ofGraduate and Postdoctoral Studies for acceptance, the thesis entitled:Investigating the Neural Basis of Sensory Learning in a Mouse Model of Huntington’sDisease: Insights from Mesoscale Microscopysubmitted by Kai Trappenberg in partial fulfillment of the requirements forthe degree of Master of Sciencein NeurosscienceExamining Committee:Supervisor: Dr. Lynn Raymond, Professor, Psychiatry, University of British ColumbiaSupervisory Committee Member: Dr. Kurt Haas, Professor, Cellular and Physiological Sci-ences, University of British ColumbiaDr. Manu Madhav, Assistant Professor, Biomedical Engineering, University of British ColumbiaAdditional Supervisory Committee Members:Supervisory Committee Member: Dr. Stan Floresco, Professor, Psychology, University ofBritish ColumbiaiiAbstractHuntington’s disease (HD) is a neurodegenerative disorder that affects numerous brain func-tions, yet how altered sensory processing contributes to behavioural and learning deficitsremains poorly understood. Previous wide-field mesoscale imaging and electrophysiologi-cal recordings from anesthetized HD model mice revealed that sensory stimulation inducedwidespread, and prolonged cortical activity in more brain regions compared to wildtype(WT) littermates. Further imaging of awake mice produced similar results, suggesting thatHD 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 acu…
has type: Thesis/Dissertation
date issued: 2025-05
is shown at: 10.14288/1.0448415
language: eng
degree discipline: Neuroscience
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Raymond, Lynn A.
type: Text
identifier URI: http://hdl.handle.net/2429/90645