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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eLife Sciences Publications Ltd
2024-03-01
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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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language | English |
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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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