Slow and fast cortical cholinergic arousal is reduced in a mouse model of focal seizures with impaired consciousness.

Autor:	Sieu LA; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Singla S; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Liu J; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Zheng X; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Sharafeldin A; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Chandrasekaran G; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Valcarce-Aspegren M; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Niknahad A; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Fu I; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Doilicho N; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Gummadavelli A; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., McCafferty C; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anatomy and Neuroscience Program, University College Cork, Cork, Ireland., Crouse RB; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA., Perrenoud Q; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA., Picciotto MR; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA., Cardin JA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA., Blumenfeld H; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: hal.blumenfeld@yale.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Dec 05; Vol. 43 (12), pp. 115012. Date of Electronic Publication: 2024 Dec 05.
DOI:	10.1016/j.celrep.2024.115012
Abstrakt:	Patients with focal temporal lobe seizures often experience loss of consciousness associated with cortical slow waves, like those in deep sleep. Previous work in rat models suggests that decreased subcortical arousal causes depressed cortical function during focal seizures. However, these studies were performed under light anesthesia, making it impossible to correlate conscious behavior with physiology. We show in an awake mouse model that electrically induced focal seizures in the hippocampus cause impaired behavioral responses to auditory stimuli, cortical slow waves, and reduced mean cortical high-frequency activity. Behavioral responses are related to cortical cholinergic release at two different timescales. Slow state-related decreases in acetylcholine correlate with overall impaired behavior during seizures. Fast phasic acetylcholine release is related to variable spared or impaired behavioral responses with each auditory stimulus. These findings establish a strong relationship between decreased cortical arousal and impaired consciousness in focal seizures, which may help guide future treatment. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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