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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Comparative analysis |
|---|---|
| Population | Rat brain |
| Interventions | Ketamine Isoflurane |
| Topics | Esketamine Ketamine |
| Keywords | Anesthetics General anesthesia Anesthetic drugs Sedation Brain science Neurobiology Brain mechanisms Neural pathways Brain activity Unconsciousness States of consciousness Altered states Awareness Pharmacology Drug mechanisms Drug action Pharmacodynamics Drug research |
| Citations | 1 |
| Key points | 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.