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

Author:

Hu Yue1ORCID,Du Wenjie1,Qi Jiangtao1,Luo Huoqing2,Zhang Zhao1,Luo Mengqiang1,Wang Yingwei1ORCID

Affiliation:

1. Department of Anesthesiology, Huashan Hospital, Fudan University

2. School of Life Science and Technology, ShanghaiTech University

Abstract

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.

Funder

National Natural Science Foundation of China

Shanghai Municipal Key Clinical Specialty

Foundation of Shanghai Municipal Science and Technology Medical Innovation Research Project

Publisher

eLife Sciences Publications, Ltd

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