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Michelson, Nicholas

University of British Columbia

Advances in neural imaging and recording technology have enabled the study of large-scale neural dynamics, revealing that various behaviors, such as decision-making or spontaneous movements, are associated with widespread cortical activation. Mesoscale calcium imaging provides an opportunity to assess these distributed cortical networks. This dissertation focuses on developing methods to study neural activity across the dorsal cortex of mice during social interactions and automatic movements. The methods described in this thesis open the door for the investigation of mesoscale cortical function in genetic mouse models of neurological disorders such as autism spectrum disorders or obsessive-compulsive disorders. First, I use widefield fluorescence imaging to compare new AAV-mediated approaches for expressing the calcium indicator, GCaMP6s, against transgenic expression methods. This functional comparison includes in vivo measurements to assess basal fluorescence brightness, visual stimulus-evoked sensory responses, magnitude of spontaneous activity fluctuations, and functional correlations across the cortex. This work establishes the systemic administration of AAV-PHP.eB-hSyn-GCaMP6s through tail-vein injection as a viable strategy for mesoscale cortical calcium imaging applications and benchmarks the performance of three commonly used transgenic models for these applications as well. Next, I develop a method to image mesoscale cortical calcium imaging across the brains of two mice simultaneously, while the mice are engaged in a constrained face-to-face social interaction. This is achieved by mounting one animal on a motor-controlled rail and varying the distance between each animal. Cross-brain measurements are assessed, including correlations in activity and behavior induced cortical responses. This work introduces a novel approach to study mesoscale cortical calcium imaging during social interaction and presents instructions for assembling a low-cost Raspberry Pi-based mesoscale imaging system. Finally, I employ a simple method to stimulate innate brainstem-mediated grooming behaviors while measuring cortical activity. Cortical representations of grooming behaviors were observed both at a mesoscale network-level and single-cell resolution. Mesoscale cortical activation was most prominent at the onset of grooming episodes and declined to baseline levels despite continuous engagement in the behavior. These findings help to frame the impact of forms of automatic movements on large scale cortical ensembles and suggest they engage specific and transient cellular and regional cortical ensembles.

Text

2025-04-08

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/90606

Neuroscience

University of British Columbia

UBCV

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