Decreased subcortical cholinergic arousal in focal seizures.

Motelow JE, Li W, Zhan Q, Mishra AM, Sachdev RN, Liu G, Gummadavelli A, Zayyad Z, Lee HS, Chu V, Andrews JP, Englot DJ, Herman P, Sanganahalli BG, Hyder F, Blumenfeld H
Neuron. 2015 85 (3): 561-72

PMID: 25654258 · PMCID: PMC4319118 · DOI:10.1016/j.neuron.2014.12.058

Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function, including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a critical mechanism for loss of consciousness in focal temporal lobe seizures.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (10)

Animals Arousal Brain Stem Cholinergic Neurons Female Magnetic Resonance Imaging Organ Culture Techniques Rats Rats, Sprague-Dawley Seizures

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