Date of Award
6-19-2024
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Local neural circuitry and global neural networks in the brain are often investigated using mesoscopic, hemodynamic imaging such as optical intrinsic signal (OIS) imaging or functional magnetic resonance imaging (fMRI), relying on oximetric signals as proxies of neural activity. However, the tight neurovascular coupling that ties regional changes in blood flow to changes in neural activity in normal states can be severely disrupted in disease states. I show that neurovascular coupling is significantly interrupted in mouse models of Cantu syndrome, a rare disease caused by gain-of-function mutations in ATP-sensitive potassium (KATP) channels. Such marked disruptions in neurovascular coupling in disease states like Cantu motivate the direct measurement of neural activity to examine changes in local circuits and global networks in neurovascular disease, such as stroke. I then demonstrate that minute increases in stroke size in mice can elicit very different profiles of repair and recovery, and that early changes in spatiotemporal dynamics of both local circuits and global networks predict long-term functional outcome after stroke. Together, these results add to our understanding of neurovascular coupling, raise concerns about the validity of hemodynamic signals as surrogate measures of neural activity in disease states, and help to elucidate early mechanisms of repair in injured neural circuits and networks.
Language
English (en)
Chair
Jin-Moo Lee