Comparative Brain-Wide Mapping of Ketamine and Isoflurane-Activated Nuclei and Functional Networks
Yue Hu, Wenjie Du, Jiangtao Qi, Huoqing Luo, Zhao Zhang, Mengqiang Luo, Yingwei Wang
bioRxiv Preprint Server June 3, 2023 preprint DOI: 10.1101/2023.06.03.543576 via bioRxiv
Summary
AI-generated from the abstractKetamine and isoflurane, two common general anesthetics, produce unconsciousness through different brain mechanisms. Ketamine activates many cortical and subcortical regions involved in sensory, motor, emotional, and reward processing, with the temporal association areas acting as a strong hub, suggesting a top-down mechanism affecting consciousness by targeting higher-order cortical networks. Isoflurane predominantly influences hypothalamic regions controlling neuroendocrine, autonomic, and homeostatic functions, with the locus coeruleus as a connector hub, indicating a bottom-up mechanism. Both anesthetics also share effects on sensory, memory, reward, and autonomic pathways.
Study at a glance
| Characteristics | Comparative analysis |
|---|---|
| Population | Rat brain |
| Interventions | Ketamine Isoflurane |
| Keywords | Anesthetics General anesthesia Anesthetic drugs Sedation Neuroscience |
| Citations | 1 |
| Key finding | Ketamine and isoflurane induce unconsciousness through distinct mechanisms—ketamine via a top-down cortical network effect and isoflurane via a bottom-up hypothalamic and brainstem effect—while also sharing effects on several neural pathways. |
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 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.