Cholinergic Neurotransmission In Partial Limbic Seizures

Cholinergic Neurotransmission in Partial Limbic Seizures. Geoffrey Liu, Joshua E. Motelow, Wei Li, Qiong Zhan, Asht M. Mishra, Robert N. S. Sachdev, Abhijeet Gummadavelli, Zaina Zayyad, Hyun Seung Lee, Victoria Chu, John P. Andrews, Dario J. Englot, Peter Herman, Basavaraju G. Sanganahalli, Fahmeed Hyder, Hal Blumenfeld. 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 enzymebased 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.