Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain

Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the mouse brain, utilizing hierarchical...

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Main Authors: Yue Hu, Wenjie Du, Jiangtao Qi, Huoqing Luo, Zhao Zhang, Mengqiang Luo, Yingwei Wang
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/88420
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author Yue Hu
Wenjie Du
Jiangtao Qi
Huoqing Luo
Zhao Zhang
Mengqiang Luo
Yingwei Wang
author_facet Yue Hu
Wenjie Du
Jiangtao Qi
Huoqing Luo
Zhao Zhang
Mengqiang Luo
Yingwei Wang
author_sort Yue Hu
collection DOAJ
description Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the mouse brain, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings reveal that KET activates a wide range of brain regions, notably in the cortical and subcortical nuclei involved in sensory, motor, emotional, and reward processing, with the temporal association areas (TEa) as a strong hub, suggesting a top-down mechanism affecting consciousness by primarily targeting higher order cortical networks. In contrast, ISO predominantly influences brain regions in the hypothalamus, impacting neuroendocrine control, autonomic function, and homeostasis, with the locus coeruleus (LC) as a connector hub, indicating a bottom-up mechanism in anesthetic-induced unconsciousness. KET and ISO both activate brain areas involved in sensory processing, memory and cognition, reward and motivation, as well as autonomic and homeostatic control, highlighting their shared effects on various neural pathways. In conclusion, our results highlight the distinct but overlapping effects of KET and ISO, enriching our understanding of the mechanisms underlying general anesthesia.
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spelling doaj.art-59391f81b3664519af2d5bc105a274202024-03-21T16:35:03ZengeLife Sciences Publications LtdeLife2050-084X2024-03-011210.7554/eLife.88420Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brainYue Hu0https://orcid.org/0009-0009-2806-2557Wenjie Du1Jiangtao Qi2Huoqing Luo3Zhao Zhang4Mengqiang Luo5Yingwei Wang6https://orcid.org/0000-0003-1633-8834Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaDepartment of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, ChinaKetamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the mouse brain, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings reveal that KET activates a wide range of brain regions, notably in the cortical and subcortical nuclei involved in sensory, motor, emotional, and reward processing, with the temporal association areas (TEa) as a strong hub, suggesting a top-down mechanism affecting consciousness by primarily targeting higher order cortical networks. In contrast, ISO predominantly influences brain regions in the hypothalamus, impacting neuroendocrine control, autonomic function, and homeostasis, with the locus coeruleus (LC) as a connector hub, indicating a bottom-up mechanism in anesthetic-induced unconsciousness. KET and ISO both activate brain areas involved in sensory processing, memory and cognition, reward and motivation, as well as autonomic and homeostatic control, highlighting their shared effects on various neural pathways. In conclusion, our results highlight the distinct but overlapping effects of KET and ISO, enriching our understanding of the mechanisms underlying general anesthesia.https://elifesciences.org/articles/88420c-Fosketamineisofluranefunctional network
spellingShingle Yue Hu
Wenjie Du
Jiangtao Qi
Huoqing Luo
Zhao Zhang
Mengqiang Luo
Yingwei Wang
Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
eLife
c-Fos
ketamine
isoflurane
functional network
title Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
title_full Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
title_fullStr Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
title_full_unstemmed Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
title_short Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
title_sort comparative brain wide mapping of ketamine and isoflurane activated nuclei and functional networks in the mouse brain
topic c-Fos
ketamine
isoflurane
functional network
url https://elifesciences.org/articles/88420
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