Date of Award

January 2015

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Hal Blumenfeld

Subject Area(s)

Neurosciences, Medicine

Abstract

Partial limbic seizures impair consciousness, but the mechanism of impairment is not known. Most views hold that structures necessary for consciousness are disrupted by overexcitation from spread of seizure activity. Against this view, we hypothesize that partial limbic seizures cause pathological long-range inhibition of cortical activity. Using a rat model for partial limbic seizures, we demonstrate BOLD fMRI signal increases in the hippocampal seizure focus, but decreases in arousal promoting regions such as the thalamus and midbrain tegmentum. Second, direct single unit recordings from cholinergic neurons in two arousal nuclei, the basal forebrain and the pedunculopontine tegmental nuclei, demonstrate suppressed firing during seizures. Finally, using enzyme-based amperometry, we probe levels of the arousal neurotransmitter acetylcholine in the cortex and thalamus and observe decreased cholinergic neurotransmission during seizures. These findings demonstrate that an arousal center is suppressed during partial limbic seizures and suggest that decreased arousal may lead to impaired consciousness.

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