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在意识受损的局灶性癫痫发作小鼠模型中，慢波和快波皮质胆碱能觉醒降低。

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

作者信息

Sieu Lim-Anna, Singla Shobhit, Liu Jiayang, Zheng Xinyuan, Sharafeldin Abdelrahman, Chandrasekaran Ganesh, Valcarce-Aspegren Marcus, Niknahad Ava, Fu Ivory, Doilicho Natnael, Gummadavelli Abhijeet, McCafferty Cian, Crouse Richard B, Perrenoud Quentin, Picciotto Marina R, Cardin Jessica A, Blumenfeld Hal

机构信息

Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.

Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anatomy and Neuroscience Program, University College Cork, Cork, Ireland.

出版信息

Cell Rep. 2024 Dec 24;43(12):115012. doi: 10.1016/j.celrep.2024.115012. Epub 2024 Dec 5.

DOI:10.1016/j.celrep.2024.115012
PMID:39643969
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11817788/
Abstract

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.

摘要

患有局灶性颞叶癫痫的患者经常会经历与皮层慢波相关的意识丧失，类似于深度睡眠时的情况。此前在大鼠模型中的研究表明，皮层下觉醒降低会导致局灶性癫痫发作期间皮层功能受到抑制。然而，这些研究是在轻度麻醉下进行的，因此无法将有意识行为与生理状况联系起来。我们在清醒小鼠模型中发现，海马体中电诱导的局灶性癫痫发作会导致对听觉刺激的行为反应受损、皮层慢波以及平均皮层高频活动降低。行为反应在两个不同的时间尺度上与皮层胆碱能释放有关。与慢状态相关的乙酰胆碱减少与癫痫发作期间整体行为受损相关。快速的相位性乙酰胆碱释放与每次听觉刺激时行为反应的可变保留或受损有关。这些发现确立了局灶性癫痫发作中皮层觉醒降低与意识受损之间的紧密关系，这可能有助于指导未来的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/49661df08f11/nihms-2044443-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/6f28f3e23442/nihms-2044443-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/b827e907f2b9/nihms-2044443-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/21ffc3026614/nihms-2044443-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/ac1802821bc6/nihms-2044443-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/49661df08f11/nihms-2044443-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/6f28f3e23442/nihms-2044443-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/b827e907f2b9/nihms-2044443-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/21ffc3026614/nihms-2044443-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/ac1802821bc6/nihms-2044443-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad34/11817788/49661df08f11/nihms-2044443-f0005.jpg

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Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures.意识障碍性啮齿动物失神发作时皮质和丘脑神经元的活性降低但多样化。
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Human visual consciousness involves large scale cortical and subcortical networks independent of task report and eye movement activity.人类视觉意识涉及大规模的皮质和皮质下网络，独立于任务报告和眼球运动活动。
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