Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain.
Yue Hu, Wenjie Du, Jiangtao Qi, Huoqing Luo, Zhao Zhang, Mengqiang Luo, Yingwei Wang
Elife March 21, 2024 DOI: 10.7554/eLife.88420 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Comparative animal study Peer reviewed |
|---|---|
| Population | Mouse brain |
| Interventions | Ketamine Isoflurane |
| Topics | Ketamine Esketamine |
| Keywords | C-fos Functional network Isoflurane Anesthesia anaesthesia Anesthetic Anaesthetic Neuroscience neurobiology Brain research Neural science Consciousness unconsciousness Awareness Drug mechanisms Animal studies mouse |
| Citations | 27 |
| Key points | Ketamine activates higher-order cortical networks in a top-down manner while isoflurane primarily affects hypothalamic and autonomic regions in a bottom-up manner, yet both anesthetics share effects on sensory, cognitive, and reward 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 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.