Abstract

My thesis has centered on developing innovative optical imaging technology for 1) understanding neurophysiological processes in the brain and 2) endogenous mechanisms of plasticity after stroke. Towards the first goal, local changes in blood oxygenation and brain energy utilization are coupled to changes in neuronal activity (neurovascular coupling(NVC) and neurometabolic coupling(NMC)). However, a cohesive link between how local changes in neuronal activity manifest as changes in metabolic and hemodynamic signaling has not been established, in part due to technological limitations. I leveraged the red-shifted genetically-encoded calcium indicator, jRGECO1a, along with dual-fluorophore wide-field optical imaging(2F-WFOI) of spontaneous calcium, flavoprotein autofluorescence (as a measure of oxidative metabolism) and blood oxygenation in mice. I demonstrate regional differences in NVC and NMC in the awake mouse brain, and that anesthesia profoundly altered NVC but not NMC. Towards the second goal, parvalbumin inhibitory interneurons(PV-INs) are known to mediate several forms of activity-dependent plasticity. However, it is unknown whether PV-INs mediate brain repair processes after stroke. I created a novel imaging system for all-optical neuronal probing via optogenetic targeting of PV-INs and mesoscopic imaging of excitatory activity via jRGECO1a. Photostimulation over a grid in the left hemisphere allowed for visualizing a whole-cortex “PV connectome”. In healthy mice, PV-INs extend ipsilateral inhibitory influences spanning several mm and region-dependent interhemispheric inhibition. Photothrombosis of left forepaw cortex resulted in decreased effective connectivity cortex-wide at week 1. Recovery following stroke was associated with global reestablishment of PV-based inhibition. Future work will determine a causal role of PV-INs on recovery.

Committee Chair

Adam Bauer

Committee Members

Jin-Moo Lee; Quing Zhu; Shannon Macauley; Song Hu

Degree

Doctor of Philosophy (PhD)

Author's Department

Biomedical Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

8-11-2025

Language

English (en)

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Available for download on Sunday, August 08, 2027

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