ORCID

http://orcid.org/0000-0001-8787-0858

Date of Award

Winter 12-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Macroscopic recordings of brain activity (e.g. fMRI, EEG) are a sensitive biomarker of the neural networks supporting neurocognitive function. However, it remains largely unclear what mechanisms mediate changes in macroscale networks after focal brain injuries like stroke, seizure, and TBI. Recently, optical neuroimaging in animal models has emerged as a powerful tool to begin addressing these questions. Using widefield imaging of cortical calcium dynamics in mice, this dissertation investigates the mechanisms by which focal disruptions in activity alter brain-wide functional dynamics. In two chapters, I demonstrate 1) that focal sensory stimulation elicits state-dependent, global slow waves propagating from primary somatosensory cortex (S1). Using a focal ischemic stroke model, I show that bilateral activation of somatosensory cortices is required for initiating global SWs, while spontaneous SWs are generated independent of S1. 2) That regional disruption of cortical excitability induces widespread changes across cortical networks, using chemogenetic manipulation of parvalbumin interneurons to model focal epileptiform activity in S1. We further show that local imbalances in excitability propagate differentially through intra- and interhemispheric connections, and can induce plasticity in large-scale networks. These studies begin to define the mechanisms of macro-scale network disruption after focal injuries, adding to our understanding of how local cortical circuits modulate global brain networks.

Language

English (en)

Chair and Committee

Jin-Moo Lee

Committee Members

Adam Bauer

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